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Sample records for folic acid antagonists

  1. 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 ...

  2. 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 ...

  3. Folic Acid

    MedlinePlus

    ... doctor what vitamins and supplements you might need. Return to top More information on folic acid For more information about folic ... Bifida Association of America Phone: 800-621-3141 Return to top Share this information! The information on our website is provided by ...

  4. Exposure to folic acid antagonists during the first trimester of pregnancy and the risk of major malformations

    PubMed Central

    Matok, Ilan; Gorodischer, Rafael; Koren, Gideon; Landau, Daniella; Wiznitzer, Arnon; Levy, Amalia

    2009-01-01

    AIM To investigate the safety of folic acid antagonists during the first trimester of pregnancy in a large cohort. METHODS Computerized databases for medications dispensed from 1998 to 2007 to women registered in ‘Clalit’ HMO, Israel southern district, was linked with maternal and infant hospitalization records, and to therapeutics abortions data. The risk for adverse pregnancy outcomes of folic acid antagonists exposure was assessed by adjusting for known confounders. RESULTS Eighty-four thousand, eight hundred and twenty-three infants were born and 998 therapeutic abortions took place; 571 fetuses and infants were exposed to one or more folic acid antagonists in the first trimester of pregnancy. Exposure was associated with an overall increased risk of congenital malformations [odds ratio (OR) 2.43, 95% confidence interval (CI) 1.92, 3.08], due mainly to increased risk for neural tube (adjusted OR 6.5, 95% CI 4.34, 9.15) and cardiovascular defects (OR 1.76, CI 1.05, 2.95). CONCLUSION First-trimester exposure to folic acid antagonists is associated with increased risk of congenital malformations. PMID:20002091

  5. Facts about Folic Acid

    MedlinePlus

    ... Partners About Us Information For... Media Policy Makers Facts About Folic Acid Language: English Español (Spanish) Recommend ... a woman needs 400 micrograms (mcg) every day. Facts About Folic Acid Download and print this fact ...

  6. Folic acid - test

    MedlinePlus

    ... folic acid before and during pregnancy helps prevent neural tube defects, such as spina bifida. Women who are pregnant ... take more if they have a history of neural tube defects in earlier pregnancies. Ask your provider how much ...

  7. Circulating folic acid in plasma: relation to folic acid fortification

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The implementation of folic acid fortification in the United States has resulted in unprecedented amounts of this synthetic form of folate in the American diet. Folic acid in circulation may be a useful measure of physiologic exposure to synthetic folic acid, and there is a potential for elevated co...

  8. Folic Acid Quiz

    MedlinePlus

    ... half of all the pregnancies in the United States are unplanned. Remember, neural tube defects occur before many women know that they are pregnant. Close × Answer: A CORRECT: While it's important to eat a healthy diet, the EASIEST way to get the right amount of folic acid everyday is to take ...

  9. Folic acid requirements of broilers.

    PubMed

    Whitehead, C C; McCormack, H A; Rennie, J S; Frigg, M

    1995-03-01

    1. Dietary folic acid requirements of broilers were studied in three experiments using wheat- and maize-based practical diets. Requirements were assessed on the basis of performance and metabolic criteria. 2. Growth and food conversion efficiencies were optimised with supplements of 1.5 mg folic acid/kg added to basal mash starter diets. The dietary folic acid requirement of broilers was estimated to be in the range of 1.7 to 2.0 mg/kg. 3. Red blood cell phosphoribosylpyrophosphate concentrations and dihydrofolate reductase activities did not show consistent changes over the range of dietary folate concentrations studied but plasma folate concentrations responded markedly to dietary folate supplementation. 4. Adding choline to diets in amounts greater than the normal requirement did not spare the requirement for folic acid. 5. It is suggested that minimum folic acid supplements for pelleted practical diets should be in the order of 2.5 to 3 mg/kg. PMID:7542146

  10. The importance of folic acid.

    PubMed

    Berg, M J

    1999-01-01

    Folic acid is necessary for cell development; for the metabolism of specific biochemical reactions in the body, such as the conversion of homocysteine to methionine; and for the metabolism of specific anticonvulsant drugs. Folic acid has an interrelationship with vitamin B12. A deficiency of folate increases the risk of NTDs, as well as contributing to hyperhomocystinemia, a condition associated with increased cardiovascular disease and NTDs. For the prevention of NTDs, it is recommended that a woman of childbearing age consume a daily folate intake of 400 micrograms; however, the average dietary folate intake is half that amount, and the FDA folate fortification of cereal grains adds only 100 micrograms daily. The woman in her childbearing years does not meet the recommendation with dietary and food fortification. Periconceptional folic acid supplementation is essential, because the neural tube closes 23 to 27 days after conception. Therefore, a multiple vitamin containing folic acid is the practical solution at present if the food fortification is not increased. The bioavailability of folate in the vitamin preparation is approximately double that of dietary folate. Most preparations contain 400 micrograms of folic acid, and if the woman took a multiple vitamin (400 micrograms of folate) in addition to her diet (230 micrograms of folate), she would not exceed 1000 micrograms (1 mg) daily, which is considered the upper limit of daily folate ingestion by dietary fortification and supplementation before the masking of vitamin B12 becomes a concern. However, in this group of patients, pernicious anemia is rare. Regarding cardiovascular disease in men and women, there are no long-term studies showing the benefit of folic acid in reducing the homocysteine level. At present, there are only estimations. However, they should not be ignored. Although it is not the current standard of practice, adding a multiple vitamin containing folic acid to the regimen of men and women starting anticonvulsant medication should be considered in order to prevent the folate lowering observed with such commonly used drugs as PHT and carbamazepine. Women in childbearing years should be on a folic acid supplement when taking an anticonvulsant drug. In general, it appears that all men and women would benefit from increased folate intake. This can be accomplished through vitamin supplementation when there is compliance. However, if the food fortification for folate is increased in the future, then the issue of vitamin supplementation will have to be readdressed. PMID:11252849

  11. Getting folic acid nutrition right

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  12. Folic Acid Questions and Answers

    MedlinePlus

    ... Why can’t I wait until I’m pregnant—or planning to get pregnant to start taking folic acid? A : Birth defects ... time soon. Q: I'm planning to get pregnant this month. Is it too late to start ...

  13. Folic acid and birth defect prevention

    MedlinePlus

    ... of certain birth defects. These include spina bifida, anencephaly, and some heart defects. Experts recommend women who ... Women who have had a baby with a neural tube defect may need a higher dose of folic acid. ...

  14. Folic acid: miscarriages, anomalies, thromboses, cancers.

    PubMed

    Thurmon, T F

    2001-02-01

    Folic acid is an essential micronutrient that merits special attention. In spite of plentiful sources in a balanced diet, recent data indicate that folic acid intake of many persons has long been inadequate. To some degree, this is due to destruction of folic acid by storage and processing of foodstuffs and to dietary practices that vary from recommendations. However, the common hereditary thermolabile variant of methylenetetrahydrofolate reductase (MTHFR) imposes an increased folic acid requirement which, if not met, may result in recurrent early pregnancy loss, anomalous progeny, thrombotic disorders, and cancers. There are recent reports that folic acid metabolism is also altered by other hereditary variations of MTHFR and other enzymes involved in folic acid metabolism. Optimal management requires dietary guidance and, for many patients, folate supplements. Caution is required because mandated folate fortification of grain products may produce levels that are inadequate for some patients and excessive for others. Laboratory tests for red cell folate and serum homocysteine are valuable adjuncts. PMID:11261364

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  16. Folic Acid Intake and Spina Bifida in the Era of Dietary Folic Acid Fortification

    PubMed Central

    Ahrens, Katherine; Yazdy, Mahsa M.; Mitchell, Allen A.; Werler, Martha M.

    2016-01-01

    Background The US Food and Drug Administration mandated that enriched grain products be fortified with folic acid by 1998. We evaluated whether intake of folic acid from supplements and diet was associated with a reduction in spina bifida in the setting of folic acid fortification. Methods Data were collected as part of the Slone Birth Defects Study from 1998 to 2008. Mothers of infants with and without birth defects were interviewed within 6 months of delivery about pregnancy exposures, including details of diet and vitamin intake. Dietary natural folate and synthetic folic acid from fortification were combined into a single, weighted measure—dietary folate equivalent. Periconceptional folic acid supplementation and dietary folate consumption were compared between 205 mothers of spina bifida cases and 6357 mothers of nonmalformed controls. Relative risks of a spina bifida-affected birth were estimated with odds ratios (ORs) and 95% confidence intervals (CIs). Results Spina bifida was not associated with regular folic acid supplementation (≥4 days per week) either around the time of conception (adjusted OR = 1.1 [95% CI = 0.74 –1.7]) or initiated in early pregnancy (0.79 [0.54–1.2]). After adjustment for confounders, a 13% reduced odds of spina bifida was estimated for each 100-µg increase in daily dietary folate equivalent consumed. Conclusions In the setting of folic acid fortification of grains, our data suggest that folic acid supplementation does not appear to offer further benefit for reducing risk of spina bifida. Rather, the folate-associated benefit on spina bifida risk was found with increasing amounts of dietary folic acid consumed, regardless of folic acid supplementation level. PMID:21659881

  17. Folic acid in ruminant nutrition: a review.

    PubMed

    Ragaller, Veronika; Hüther, Liane; Lebzien, Peter

    2009-01-01

    Folic acid plays an essential role in DNA and methionine metabolism. Micro-organisms in the rumen can synthesise folates, but it has not been verified that these amounts are sufficient to achieve the best efficiency of dairy cows. However, the amount of folates synthesised in the rumen could possibly, to some extent, be affected by the forage:concentrate ratio. Degradation of orally supplemented folic acid in the rumen seems to be very high (about 97%), as supplementation of folic acid hardly increases folate concentrations in the digesta at the duodenum. However, it must be considered that dietary supplements of folic acid higher than 0.5 mg/kg body weight increased serum folate concentrations in all available studies and milk folate concentrations in most studies. Additionally, milk production tended to be increased in some studies. Therefore, degradation of folic acid in the rumen may be overestimated as folates can be absorbed at the proximal duodenum. For future research it is necessary to consider the whole flow and the metabolic pathways of folates from the rumen to duodenum, blood, tissue, milk and transfer to calf to declare requirement values for cows. Consequently, the present review discusses current knowledge and emphasises areas for future research. PMID:18775098

  18. Folic acid supplementation--when and how.

    PubMed

    Schwarz, R H; Johnston, R B

    1996-11-01

    The periconceptional intake of 400 micrograms of folic acid can prevent 50-70% of neural tube defects. It is difficult to achieve this intake with diet alone, even with the recently approved levels for grain-food fortification. Therefore, a daily multivitamin with folic acid is recommended for all women of childbearing potential. Obstetrician-gynecologists should exercise every opportunity to educate their patients to this end. Although raised as a concern, the potential of masking the megaloblastic anemia of pernicious anemia is unlikely with these levels of supplementation, and considering the rarity of the disease in women of reproductive age. PMID:8885933

  19. Preventing birth defects with folic acid.

    PubMed

    Stein, Quinn; Keppen, Laura; Watson, William J

    2002-09-01

    There a few birth defects known to be preventable, but neural tube defects (NTDs) are one group of congenital anomalies that can potentially be prevented. When 400 micrograms of maternal periconceptional folic acid is taken daily, it can prevent many neural tube-related birth defects and thus reduce morbidity and mortality due to these birth defects. Health care providers should encourage every woman of reproductive age to consume 400 micrograms of synthetic folic acid daily, not just those who are planning a pregnancy. Supplementation needs to be started prior to conception for optimal effectiveness. PMID:12360641

  20. Neural Tube Defects, Folic Acid and Methylation

    PubMed Central

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

    2013-01-01

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

  1. Contemporary Issues Surrounding Folic Acid Fortification Initiatives

    PubMed Central

    Choi, Jeong-Hwa; Yates, Zoe; Veysey, Martin; Heo, Young-Ran; Lucock, Mark

    2014-01-01

    The impact of folate on health and disease, particularly pregnancy complications and congenital malformations, has been extensively studied. Mandatory folic acid fortification therefore has been implemented in multiple countries, resulting in a reduction in the occurrence of neural tube defects. However, emerging evidence suggests increased folate intake may also be associated with unexpected adverse effects. This literature review focuses on contemporary issues of concern, and possible underlying mechanisms as well as giving consideration the future direction of mandatory folic acid fortification. Folate fortification has been associated with the presence of unmetabolized folic acid (PteGlu) in blood, masking of vitamin B12 deficiency, increased dosage for anti-cancer medication, photo-catalysis of PteGlu leading to potential genotoxicity, and a role in the pathoaetiology of colorectal cancer. Increased folate intake has also been associated with twin birth and insulin resistance in offspring, and altered epigenetic mechanisms of inheritance. Although limited data exists to elucidate potential mechanisms underlying these issues, elevated blood folate level due to the excess use of PteGlu without consideration of an individual’s specific phenotypic traits (e.g. genetic background and undiagnosed disease) may be relevant. Additionally, the accumulation of unmetabolized PteGlu may lead to inhibition of dihydrofolate reductase and other enzymes. Concerns notwithstanding, folic acid fortification has achieved enormous advances in public health. It therefore seems prudent to target and carefully monitor high risk groups, and to conduct well focused further research to better understand and to minimize any risk of mandatory folic acid fortification. PMID:25580388

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

    PubMed Central

    Dugbaza, Jacinta; Cunningham, Judy

    2012-01-01

    Mandatory folic acid fortification of wheat flour for making bread was implemented in Australia in September 2009, to improve the dietary folate status of women of child-bearing age, and help reduce the incidence of neural tube defects in the population. This paper presents estimates of folic acid intake in the target population and other subgroups of the Australian population following implementation of the mandatory folic acid fortification standard. In June/July 2010 one hundred samples from seven bread categories were purchased from around the country and individually analysed for the amount of folic acid they contained. A modification to the triple enzyme microbiological method was used to measure folic acid in the individual bread samples. The folic acid analytical values together with national food consumption data were used to generate estimates of the population's folic acid intake from fortified foods. Food Standards Australia New Zealand's (FSANZ) custom-built dietary modelling program (DIAMOND) was used for the estimates. The mean amount of folic acid found in white bread was 200 μg/100 g which demonstrated that folic-acid-fortified wheat flour was used to bake the bread. The intake estimates indicated an increase in mean folic acid intake of 159 μg per day for the target group. Other sub-groups of the population also showed increases in estimated mean daily intake of folic acid. PMID:22957218

  3. The primary prevention of birth defects: Multivitamins or folic acid?

    PubMed

    Czeizel, Andrew E

    2004-01-01

    Periconceptional use of folic acid alone or in multivitamin supplements is effective for the primary prevention of neural-tube defects. The Hungarian randomized and two-cohort controlled trials showed that periconceptional multivitamin supplementation can reduce the occurrence of some other structural birth defects, i.e. congenital abnormalities. These findings were supported by many, but not all observational studies. Recently there have been two main debated questions. The first one is whether the use of folic acid alone or folic acid-containing multivitamins is better. The second one is connected with the dilemma of whether high dose of folic acid (e.g. 5 mg) might be better than a daily multivitamin with 0.4 - 0.8 mg of folic acid. Comparison of the pooled data of two Hungarian trials using a multivitamin containing 0.8 mg folic acid and the data of the Hungarian Case-Control Surveillance of Congenital Abnormalities using high dose of folic acid seemed to be appropriate to answer these questions. Multivitamins containing 0.4 - 0.8 mg of folic acid were more effective for the reduction of neural-tube defects than high dose of folic acid. Both multivitamins and folic acid can prevent some part of congenital cardiovascular malformations. Only multivitamins were able to reduce the prevalence at birth of obstructive defects of urinary tract, limb deficiencies and congenital pyloric stenosis. However, folic acid was effective in preventing some part of rectal/anal stenosis/atresia, and high dose of folic acid had effect in preventing some orofacial clefts. The findings are consistent that periconceptional multivitamin and folic acid supplementation reduce the overall occurrence of congenital abnormalities in addition to the demonstrated effect on neural-tube defects. PMID:15912190

  4. Regulation of human jejunal glycolytic enzymes by oral folic acid

    PubMed Central

    Rosensweig, Norton S.; Herman, Robert H.; Stifel, Fred B.; Herman, Yaye F.

    1969-01-01

    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-phosphate aldolase, and fructose diphosphate aldolase, and the disaccharidases, sucrase, maltase, and lactase were measured. In both the fasting patients and the normal volunteers, oral folic acid significantly increased the jejunal glycolytic enzyme activities but had no effect on disaccharidase activity. When oral folic acid was discontinued in the normal volunteers, the glycolytic enzyme activities returned to control values. In the obese patients, refeeding and folic acid caused a further increase in glycolytic enzyme activities above that seen with fasting and folic acid. In contrast to oral folic acid, intramuscular folic acid, oral vitamin B12, and oral tetracycline had no effect on glycolytic enzyme activities. These studies demonstrate that oral folic acid which is neither a substrate nor a coenzyme of these enzymes, increases human jejunal glycolytic enzyme activity in a specific fashion. This would appear to be an action of oral folic acid which has not been recognized previously. PMID:5824069

  5. Will mandatory folic acid fortification prevent or promote cancer?

    PubMed

    Kim, Young-In

    2004-11-01

    An overwhelming body of evidence for a protective effect of periconceptional folic acid supplementation against neural tube defects (NTDs) led to mandatory folic acid fortification in the United States. The effectiveness of folic acid fortification in improving folate status has already been shown to be quite striking, with a dramatic increase in blood measurements of folate in the United States. Preliminary reports also suggest a significant reduction ( approximately 15-50%) in NTDs in the United States. The success of folic acid fortification in improving folate status and in reducing NTD rates is truly a public health triumph and provides a paradigm of collaboration between science and public health policy. Although folic acid is generally regarded as safe, there continues to be concern that folic acid fortification may have adverse effects in subpopulation groups not originally targeted for fortification. In this regard, an emerging body of evidence suggests that folic acid supplementation may enhance the development and progression of already existing, undiagnosed premalignant and malignant lesions. Over the past few years, the US population has been exposed to a significant increase in folate intake, for which essentially no data on safety exist. The potential cancer-promoting effect of folic acid supplementation needs to be considered in carefully monitoring the long-term effect of folic acid fortification on the vast majority of the US population, who are not at risk of NTDs. PMID:15531657

  6. Folic acid in the prevention of birth defects.

    PubMed

    Allen, W P

    1996-12-01

    Maternal use of folic acid prior to conception reduces the risk for neural tube defects. In addition, other birth defects may be prevented by the periconceptional use of folic acid. Homocysteine-methionine metabolism appears to be altered in women with pregnancies affected by neural tube defects; however, the specific mechanisms of causation are not yet known. Fortification of flour with folic acid has been approved by the Food and Drug Administration, although at a level that still requires folic acid supplementation as recommended by the Public Health Service for all women of childbearing age to prevent neural tube defects. PMID:9018449

  7. Folic Acid Determination Using Electrochemical Sensors

    PubMed Central

    Mirmoghtadaie, Leila; Shamaeizadeh, Nahal; Mirzanasiri, Nooshin

    2015-01-01

    Folic acid (FA) is a water soluble vitamin that exists in many natural species. The lack of FA causes some deficiencies in the human body, so finding a simple and sensitive method for determining the FA is important. One of the modern techniques which overcome the disadvantages of conventional determination methods is the sensors. Possibility of miniaturization, the development of microfabricated electrochemical (EC) sensors has resulted in high sensitivity, portability, improved performance and spatial resolution, low power consumption, and the opportunity for integration with other technologies made Micro-Electrical-Mechanical Systems-based EC sensors suitable to identify low concentration analytes and microorganisms in a variety of mediums. PMID:26605021

  8. A survey of folic acid use in primigravid women.

    PubMed

    Wilton, Diane C; Foureur, Maralyn J

    2010-06-01

    A convenience sample of 320 consecutive primigravid women attending the antenatal clinic of a large Sydney tertiary referral hospital were invited to take part in a survey of folic acid use in pregnancy. The aim of the survey was to determine the number of primigravid women who commenced taking folic acid supplementation at least 1 month prior to conception. In addition the survey sought information on women's source of knowledge about the need for folic acid in pregnancy and whether their pregnancy was planned or unplanned. 295 women qualified to be included in the survey. While 88.1% of women took folic acid at some time prior to and/or during the first trimester, only 23.4% were found to have taken folic acid at least 1 month prior to conception. Of women with a planned birth only 34.5% commenced folic acid prior to conception. This survey adds further weight to the decision of the Australian Government to mandate for fortification of bread-making flour with folic acid, due to commence in September 2009. However, even with folic acid fortified food, health professionals need to continue to advise women to take supplements prior to conception and for at least 12 weeks into their pregnancy to prevent neural tube defects. PMID:19828392

  9. 21 CFR 172.345 - Folic acid (folacin).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies are available from the... HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Special Dietary and Nutritional Additives § 172.345 Folic acid (folacin). Folic acid (CAS Reg. No....

  10. 21 CFR 172.345 - Folic acid (folacin).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies are available from the... HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Special Dietary and Nutritional Additives § 172.345 Folic acid (folacin). Folic acid (CAS Reg. No....

  11. Folic acid use in planned pregnancy: an Italian survey.

    PubMed

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

    2013-05-01

    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

  12. Folic acid: to fortify or not to fortify? An examination of selected national policies towards mandatory folic acid fortification

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many national authorities are reviewing their policy towards mandatory folic acid fortification of staple foods in response to epidemiological evidence of the relationship between folic acid and neural tube defects (NTDs). However, there are scientific, ethical and technical challenges associated wi...

  13. Folic acid: a public-health challenge.

    PubMed

    Eichholzer, Monika; Tönz, Otmar; Zimmermann, Roland

    2006-04-22

    Despite worldwide public-health campaigns recommending periconceptional daily supplementation of synthetic folic acid to reduce the risk of neural tube defects, many women are not following these recommendations. At the same time, in most European countries no decline in defects has been recorded in recent years. Vulnerable groups are those with a low standard of education, young people, and women with unplanned pregnancies. Furthermore, in most countries without mandatory fortification, the general population is not consuming the recommended 0.4 mg of food folate per day. Voluntary fortification improves the situation, but does not reach all parts of the population. In the USA, Canada, and Chile, mandatory fortification of flour substantially improved folate and homocysteine status, and neural tube defects rates fell by between 31% and 78%. Nevertheless, many countries do not choose mandatory folic acid fortification, in part because expected additional health benefits are not yet scientifically proven in clinical trials, in part because of feared health risks, and because of the issue of freedom of choice. Thus, additional creative public-health approaches need to be developed to prevent neural tube defects and improve the folate status of the general population. PMID:16631914

  14. Imaging Cancer Cells Expressing the Folate Receptor with Carbon Dots Produced from Folic Acid.

    PubMed

    Bhunia, Susanta Kumar; Maity, Amit Ranjan; Nandi, Sukhendu; Stepensky, David; Jelinek, Raz

    2016-04-01

    Development of new imaging tools for cancer cells in vitro and in vitro is important for advancing cancer research, elucidating drug effects upon cancer cells, and studying cellular processes. We showed that fluorescent carbon dots (C-dots) synthesized from folic acid can serve as an effective vehicle for imaging cancer cells expressing the folate receptor on their surface. The C-dots, synthesized through a simple one-step process from folic acid as the carbon source, exhibited selectivity towards cancer cells displaying the folate receptor, making such cells easily distinguishable in fluorescence microscopy imaging. Biophysical measurements and competition experiments both confirmed the specific targeting and enhanced uptake of C-dots by the folate receptor-expressing cells. The folic acid-derived C-dots were not cytotoxic, and their use in bioimaging applications could aid biological studies of cancer cells, identification of agonists/antagonists, and cancer diagnostics. PMID:26773979

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Lindzon, Gillian

    2007-01-01

    Folate has received international attention regarding its role in the risk-reduction of birth defects, specifically neural tube defects (NTDs). In 1998, health officials in Canada, like the United States, mandated the addition of folic acid to white flour and select grain products to increase the folate intake of reproductive-aged women. Subsequent to this initiative there has been an increase in blood folate concentrations in Canada and a 50% reduction in NTDs. Many countries, including Korea, have not mandated folic acid fortification of their food supply. Reasons vary but often include concern over the masking of vitamin B12 deficiency, a belief that folate intakes among womenare adequate, low priority relative to other domestic issues, and the philosophy that individuals have the right not to consume supplemental folic acid if they so choose. Prior to folic acid fortification of the food supply in Canada, the folate intakes of women were low, and their blood folate concentrations while not sufficiently low to produce overt signs of folate deficiency (eg. anemia) were inconsistent with a level known to reduce the risk of an NTD-affected pregnancy. The purpose of this article is to describe the role of folate during the periconceptional period, pregnancy, and during lactation. The rationale for, and history of recommending folic acid-containing supplements during the periconceptional period and pregnancy is described as is folic acid fortification of the food supply. The impact of folic acid fortification in Canada is discussed, and unresolved issues associated with this policy described. While the incidence of NTDs in Canada pre-folic acid fortification were seemingly higherthan that of Korea today, blood folate levels of Korean women are strikingly similar. We will briefly explore these parallels in an attempt to understand whether folic acid fortification of the food supply in Korea might be worth consideration PMID:20368933

  17. The role of folic acid in oral clefting.

    PubMed

    Hartridge, T; Illing, H M; Sandy, J R

    1999-06-01

    The objective of this study is to describe the role of periconceptional folic acid supplementation and assess it's potential in the prevention of foetal abnormalities, and consists of a review of the literature undertaken using an electronic and hand search. This includes research trials and methodology associated with folic acid supplementation. It is recommended that all women planning to conceive should supplement their diet with folic acid in order to prevent abnormalities in neural tube development, particularly if there is a history of a previously affected pregnancy. There is increasing evidence that folic acid supplementation may, in addition, reduce the incidence of oral facial clefting. Further research with multi-disciplinary approaches in biochemistry, genetics, gene/environment interactions, and embryology are indicated. PMID:10420245

  18. Formation of polydopamine nanofibers with the aid of folic acid.

    PubMed

    Yu, Xiang; Fan, Hailong; Wang, Le; Jin, Zhaoxia

    2014-11-10

    Polydopamine (PDA) generated by the oxidative self-polymerization of dopamine shows great potential for surface modification. Observed PDA nanostructures are nanoparticles and thin films. The formation mechanism of PDA is still unclear; thus, the manipulation of PDA nanostructures is a big challenge. In this study, we first demonstrated that folic acid shows a dramatic effect on the PDA nanostructure: New aggregated nanostructures of PDA, nanobelts and nanofibers, were generated in a dopamine/folic acid system. We hypothesized that folic acid may be involved in the stacking of protomolecules of PDA by π-π interactions and hydrogen bonding. Herein we describe the first experimental strategy to manipulate the aggregation of PDA by using small molecules. This study not only provides a new method for generating PDA nanofibers, which are proposed bioorganic electronic materials, but also a possible way to understand the formation mechanism of PDA and its analogues in nature, melanins. PMID:25146565

  19. Adsorptive stripping voltammetric assay of folic acid in human serum.

    PubMed

    Fernandez Alvarez, J M; Costa Garcia, A; Miranda Ordieres, A J; Tunn Blanco, P

    1988-01-01

    Folic acid was voltammetrically measured after preconcentration by adsorption at the static mercury drop electrode. Phase selective AC voltammetry provided the most sensitive stripping signal. After previous analyte extraction, using liquid-solid extraction with a C-18 reversed phase cartridge, the method was suitable for folic acid measurement in human serum. The detection limit was 5.9 x 10(-9) M with an overall precision of 9.9% (R.S.D.; n = 7) at the concentration level of 1.0 x 10(-7) M with a mean recovery of 57%. PMID:16867338

  20. Efficacy of adding folic acid to foods.

    PubMed

    Fajardo, Violeta; Varela-Moreiras, Gregorio

    2012-06-01

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

  1. Evaluation of ascorbic acid in protecting labile folic acid derivatives.

    PubMed Central

    Wilson, S D; Horne, D W

    1983-01-01

    The use of ascorbic acid as a reducing agent to protect labile, reduced derivatives of folic acid has been evaluated by high-performance liquid chromatographic separations and Lactobacillus casei microbiological assay of eluate fractions. Upon heating for 10 min at 100 degrees C, solutions of tetrahydropteroylglutamic acid (H4PteGlu) in 2% sodium ascorbate gave rise to 5,10-methylene-H4PteGlu and 5-methyl-H4PteGlu. H2PteGlu acid gave rise to 5-methyl-H4PteGlu and PteGlu. 10-Formyl-H4PteGlu gave rise to 5-formyl-H4PteGlu and 10-formyl-PteGlu. 5-Formyl-H4-PteGlu gave rise to a small amount of 10-formyl-PteGlu. 5-Methyl-H4PteGlu and PteGlu appeared stable to these conditions. These interconversions were not seen when solutions of these folate derivatives were kept at 0 degrees C in 1% ascorbate. These observations indicate that elevated temperatures are necessary for the interconversions of folates in ascorbate solutions. Assays of ascorbic acid solutions indicated the presence of formaldehyde (approximately equal to 6 mM). This was confirmed by the identification of 3,5-diacetyl-1,4-dihydrolutidine by UV, visible, and fluorescence spectroscopy and by thin-layer chromatography of chloroform extracts of the reaction mixture of ascorbic acid solutions, acetylacetone, and ammonium acetate. These results indicate that solutions of sodium ascorbate used at elevated temperatures are not suitable for extracting tissue for the subsequent assay of the individual folic acid derivatives. PMID:6415653

  2. Folic acid-anchored PEGgylated phospholipid bioconjugate and its application in a liposomal immunodiagnostic assay for folic acid.

    PubMed

    Ho, Ja-an Annie; Hung, Chi-Hsiang; Wu, Li-Chen; Liao, Ming-Yuan

    2009-07-15

    A folic acid-anchored, poly(ethylene glycol)-linked (PEGgylated) phospholipid and an immunoaffinity chromatographic column were prepared and employed to develop a liposomal immunodiagnostic assay for the direct determination of folic acid (FA) in this study. Distearoylphosphatidylethanolamine-poly(ethylene glycol)2000-folic acid (DSPE-PEG2000-FA) was synthesized through carbodiimide-mediated coupling of FA and DSPE-PEG2000-amine and characterized using thin layer chromatography, 1H nuclear magnetic resonance spectroscopy, and electrospray ionization-mass spectrometry. Liposomal biolabels were constructed using the synthesized DSPE-PEG2000-FA in conjunction with other phospholipids. A stationary phase having affinity for FA was prepared by covalently linking purified anti-FA monoclonal antibodies onto N-hydroxysuccinimide-activated Sepharose beads, which were subsequently packed into a 1.9 cm diameter polypropylene column. The calibration curve for FA had a linear range from 10(-8) to 10(-4) M. The limit of detection was 6.8 ng (equivalent to 500 microL of 3.1 x 10(-8) M FA). The elution buffer (35% methanol in Tris buffered saline containing 0.1% Tween 20) also served as the regeneration buffer, which allowed the same column to be used for up to 50 times without any observable loss of reactivity. The immunoaffinity chromatographic column was reusable and capable of concentrating analytes from sample solution; in conjunction with folic acid-sensitized liposomal biolabels, however, they hold great potential as sensitive immunoaffinity assays for the determination for FA. To confirm the feasibility of using this system in the analysis of real samples, the folic acid contents of three over-the-counter vitamin supplements were tested. The recoveries of folic acid of 90-112% for these three samples were obtained, suggesting contents that were consistent with the information obtained from their nutritional facts panels. PMID:19518067

  3. Folic acid fortification: why not vitamin B12 also?

    PubMed

    Selhub, Jacob; Paul, Ligi

    2011-01-01

    Folic acid fortification of cereal grains was introduced in many countries to prevent neural tube defect occurrence. The metabolism of folic acid and vitamin B12 intersect during the transfer of the methyl group from 5-methyltetrahydrofolate to homocysteine catalyzed by B12-dependent methioine synthase. Regeneration of tetrahydrofolate via this reaction makes it available for synthesis of nucleotide precursors. Thus either folate or vitamin B12 deficiency can result in impaired cell division and anemia. Exposure to extra folic acid through fortification may be detrimental to those with vitamin B12 deficiency. Among participants of National Health And Nutrition Examination Survey with low vitamin B12 status, high serum folate (>59 nmol/L) was associated with higher prevalence of anemia and cognitive impairment when compared with normal serum folate. We also observed an increase in the plasma concentrations of total homocysteine and methylmalonic acid (MMA), two functional indicators of vitamin B12 status, with increase in plasma folate under low vitamin B12 status. These data strongly imply that high plasma folate is associated with the exacerbation of both the biochemical and clinical status of vitamin B12 deficiency. Hence any food fortification policy that includes folic acid should also include vitamin B12. PMID:21674649

  4. [Intake of folic acid in the total daily diet--effect of food preparation on its folic acid content].

    PubMed

    Müller, H

    1995-03-01

    The folic acid content of total daily diet was determined by means of high-performance liquid chromatography (HPLC). The contents of tetrahydrofolic acid (THF), 5-methyl-THF and 5-formyl-THF were differentiated. The mean of the folic acid content of the total daily diet samples determined analytically was 205 +/- 60 micrograms and the mean of the individual ingredients of the samples was 401 +/- 78 micrograms, which implies that about 50% of folic acid is destroyed by common household food preparation methods. If the contents of pteroylglutamic acid (PteGlu) and 10-formyl-PteGlu (which cannot be determined analytically) are added, it can be assumed that the folic acid content with only be reduced by about 40%. THF and 5-methyl-THF proved to be less stable than 5-formyl-THF. The monoglutamate portion of the total folat content was higher in the total diet samples than in the individual foodstuffs as a consequence of the action of the enzyme "deconjugase" which is released when the matrix of food-stuffs is destroyed. PMID:7785346

  5. 21 CFR 862.1295 - Folic acid test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Folic acid test system. 862.1295 Section 862.1295 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  6. 21 CFR 862.1295 - Folic acid test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Folic acid test system. 862.1295 Section 862.1295 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  7. 21 CFR 862.1295 - Folic acid test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Folic acid test system. 862.1295 Section 862.1295 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  8. 21 CFR 862.1295 - Folic acid test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Folic acid test system. 862.1295 Section 862.1295 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  9. 21 CFR 862.1295 - Folic acid test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Folic acid test system. 862.1295 Section 862.1295 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  10. Folic acid-Functionalized Nanoparticles for Enhanced Oral Drug Delivery

    PubMed Central

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

    2012-01-01

    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. PMID:22670575

  11. [Folic acid: Primary prevention of neural tube defects. Literature Review].

    PubMed

    Llamas Centeno, M J; Miguélez Lago, C

    2016-03-01

    Neural tube defects (NTD) are the most common congenital malformations of the nervous system, they have a multifactorial etiology, are caused by exposure to chemical, physical or biological toxic agents, factors deficiency, diabetes, obesity, hyperthermia, genetic alterations and unknown causes. Some of these factors are associated with malnutrition by interfering with the folic acid metabolic pathway, the vitamin responsible for neural tube closure. Its deficit produce anomalies that can cause abortions, stillbirths or newborn serious injuries that cause disability, impaired quality of life and require expensive treatments to try to alleviate in some way the alterations produced in the embryo. Folic acid deficiency is considered the ultimate cause of the production of neural tube defects, it is clear the reduction in the incidence of Espina Bifida after administration of folic acid before conception, this leads us to want to further study the action of folic acid and its application in the primary prevention of neural tube defects. More than 40 countries have made the fortification of flour with folate, achieving encouraging data of decrease in the prevalence of neural tube defects. This paper attempts to make a literature review, which clarify the current situation and future of the prevention of neural tube defects. PMID:26959966

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

  13. 21 CFR 172.345 - Folic acid (folacin).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION... incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies are available from the... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Folic acid (folacin). 172.345 Section 172.345...

  14. 21 CFR 172.345 - Folic acid (folacin).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION... incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies are available from the... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Folic acid (folacin). 172.345 Section 172.345...

  15. 21 CFR 172.345 - Folic acid (folacin).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Special Dietary and Nutritional... 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain copies from the United States Pharmacopeial.../federal-register/cfr/ibr-locations.html. (c) Folic acid may be added to foods subject to a standard...

  16. Folic acid conjugated ferritins as photosensitizer carriers for photodynamic therapy†

    PubMed Central

    Zhen, Zipeng; Tang, Wei; Zhang, Weizhong

    2015-01-01

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

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

  18. [Reference values of folic acid for the Venezuelan population].

    PubMed

    García-Casal, María Nieves; Carias, Diamela; Soto de Sanabria, Ingrid; Victoria López, Ana

    2013-12-01

    The review on folic acid requirements for Venezuela comprise the definitions adopted worldwide known as Dietary Reference Intakes (DRIs) that include Recommended Dietary Allowance (RDA), Estimated Average Requirement (EAR), Adequate Intake (AI) and Tolerable Upper Intake Levels (UL). In contrast with the situation in some countries, that required adjustments in fortification policies in order to avoid excessive folic acid consumption, in Venezuela several studies show an elevated prevalence of deficiency. National evidence at this point is insufficient to establish the recommendation, and as in the 2000 review of the Venezuelan RDAs, the actual recommendations are based on the reported for the United States population. The Recommended Dietary Allowances for Venezuela are 65-80 microg/day for infants less than 1 year old, 150-300 microg/day for children and 400 microg/day for adolescents and adults, increasing to 600 microg/day during pregnancy and to 500 microg/day during lactation. The estimated average requirement is 120-250 microg/day for children, 330 microg/day for adolescents, 320 microg/day for adults, 520 microg/day for pregnancy and 450 microg/day during lactation. The tolerable upper intake levels for folic acid are 300-600 microg/day for children, 800 microg/day for adolescents and 1000 microg/day for adults. During pregnancy and lactation the UL is 800 microg/day for pregnant and lactating women between 14 and 18 years of age, and 1000 microg/day for older pregnant and lactating women. The continuous evaluation of folic acid status is important to design adequate and efficient policies to control both, the deficiency and the excess of folic acid consumption. PMID:25924462

  19. Association Between Preconception Counseling and Folic Acid Supplementation Before Pregnancy and Reasons for Non-Use.

    PubMed

    Bixenstine, Paul J; Cheng, Tina L; Cheng, Diana; Connor, Katherine A; Mistry, Kamila B

    2015-09-01

    To examine the relationship between folic acid preconception counseling (PCC) and folic acid use and reasons for non-use among women with a recent live birth. We analyzed Maryland Pregnancy Risk Assessment Monitoring System (PRAMS) survey responses from 2009 to 2011 (n = 4,426, response rate = 67%). Multivariable weighted logistic regression models were used to explore associations between folic acid PCC receipt and folic acid use and reasons for non-use. Approximately 30% of women reported daily folic acid use the month before pregnancy, with lower rates among those who were <30, non-white, or unmarried; received WIC during pregnancy; had suffered a stressful event prepregnancy; smoked prepregnancy; had a previous live birth; or had an unintended pregnancy (all p < 0.05). The most common reasons for folic acid non-use were "not planning pregnancy" (61%) and "didn't think needed to take" (41%). Folic acid PCC receipt was reported by 27% of women and was associated with three times the odds of folic acid use (adjusted odds ratio [aOR] 3.15, 95% CI 2.47-4.03) and half the odds of reporting "didn't think needed to take" (aOR 0.47, 95% CI 0.28-0.78) as a reason for non-use. Less than one-third of recent Maryland mothers reported using folic acid daily before pregnancy and only 27% reported receiving folic acid PCC. However, folic acid PCC was associated with increased folic acid use and decreased reporting that women did not think they needed to take folic acid. Our data support initiatives to promote provision of folic acid PCC to all women of childbearing age. PMID:25663654

  20. Synthesis of an indole analog of folic acid

    SciTech Connect

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

    1987-06-01

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

  1. Phenytoin, folic acid and gingival enlargement: Breaking myths

    PubMed Central

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

    2014-01-01

    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. PMID:24808697

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

    PubMed Central

    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

    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. PMID:24842467

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

    SciTech Connect

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

    2010-12-01

    In this study, we report the preparation,luminescence, and targeting properties of folic acid- CdTe quantum dot conjugates. Water-soluble CdTe quantum dots were synthesized and conjugated with folic acid using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide-N-hydroxysuccinimide chemistry. The in-fluence of folic acid on the luminescence properties of CdTe quantum dots was investigated, and no energy transfer between them was observed. To investigate the efficiency of folic acid-CdTe nanoconjugates for tumor targeting, pure CdTe quantum dots and folic acid-coated CdTe quantum dots were incubated with human naso- pharyngeal epidermal carcinoma cell line with positive expressing folic acid receptors (KB cells) and lung cancer cells without expression of folic acid receptors (A549 cells). For the cancer cells with positive folate receptors (KB cells), the uptake for CdTe quantum dots is very low, but for folic acid-CdTe nanoconjugates, the uptake is very high. For the lung cancer cells without folate receptors (A549 cells), the uptake for folic acid- CdTe nanoconjugates is also very low. The results indicate that folic acid is an effective targeting molecule for tumor cells with overexpressed folate receptors.

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

    PubMed Central

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

    2015-01-01

    Introduction The intake of folic acid before conception and during the first trimester of pregnancy can prevent spina bifida. This paper describes folic acid intake in women in Gulu district in northern Uganda. Methods Structured interviews were held with 394 women attending antenatal care (ANC), 15 mothers of children with spina bifida, and 35 health workers in 2012 and 2013. SPSS16 was used for data analysis. Results 1/4 mothers of children with spina bifida took folic acid during late pregnancy, none preconception. None had knowledge about folic acid and spina bifida prevention. 33.5% of women attending ANC had ever heard about spina bifida, 1% knew folic acid intake can prevent spina bifida. 42.4% took folic acid supplements in late pregnancy, 8.1% during the first trimester, none preconception. All women said to have eaten food rich in folic acid. None were aware about fortified foods. 7% of health workers understood the importance of early folic acid intake. All health workers recommended folic acid intake to women attending ANC. 20% of the health workers and 25% of the women said folic acid supplements are not always available. Conclusion Folic acid intake is limited in northern Uganda. This is attributed to limited education and understanding of women and health workers about the importance of early folic acid intake, late presentation of women at ANC, poor supply chain and dilapidated health services caused by war and poverty. A combination of food fortification, sensitization of health workers, women, and improving folic acid supply is recommended. PMID:26090048

  5. Folic acid alone or multivitamin containing folic acid intake during pregnancy and the risk of gestational hypertension and preeclampsia through meta-analyses

    PubMed Central

    Shim, Sang-Min; Yun, Yeo-Ul

    2016-01-01

    Objective The objective of this study was to assess the effect of folic acid and multivitamin use during pregnancy on the risk of developing of hypertensive disorder of pregnancy. Methods Two reviewers independently determined all prospective cohort study, retrospective cohort study, large population based cohort study, retrospective secondary analysis, and double blinded, placebo-controlled, randomized clinical trial published using PubMed Medline database, KERIS (Korea Education and Research Information Service), Scopus, and the Cochrane Central Register of controlled trials comparing before conception throughout pregnancy intake oral multivitamin containing folic acid or folic acid alone. Meta-analyses were estimated with odds ratios and 95% confidence intervals (CIs) using random effect analysis according to heterogeneity of studies. Results Data from six effect sizes from six studies involving 201,661 patients were enrolled. These meta-analyses showed multivitamin containing folic acid or folic acid alone was not significantly effective in reducing gestational hypertension or preeclampsia incidence (odds ratio, 0.91; 95% CI, 0.81 to 1.03) than the placebo. And the difference of effective sizes of preeclampsia and gestational hypertension according to two dependent variables, multivitamin and folic acid were not significant, respectively (point estimate, 0.66; 95% CI, 0.46 to 0.96). Conclusion These meta-analyses demonstrate multivitamin containing folic acid or folic acid alone was not significantly effective in reducing gestational hypertension or preeclampsia incidence. PMID:27004201

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

  7. Imaging Pancreatic Cancer with Folic Acid Terminated Luminescent Silicon Nanocrystals

    NASA Astrophysics Data System (ADS)

    Erogbogbo, Folarin; Swihart, Mark T.

    2010-10-01

    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.

  8. Carbamazepine and folic acid in trigeminal neuralgia patients.

    PubMed Central

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

    1992-01-01

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

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

    PubMed

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

    2014-06-01

    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

  10. Folic acid deaminase activity during development in Dictyostelium discoideum.

    PubMed Central

    Kakebeeke, P I; de Wit, R J; Konijn, T M

    1980-01-01

    Folic acid attracts vegetative amoebae of Dictyostelium discoideum. Secreted by bacteria, it may act as a food-seeking device. The inactivation of this attractant is catalyzed by a deaminase. As assay has been developed to measure the folic acid deaminase activity. In addition to cell-surface an intracellular deaminase, the amoebae of D. discoideum release the enzyme into the medium. The pH optimum of the extracellular enzyme was 6.0, and higher for the cell-associated deaminases. The extracellular enzyme was secreted maximally by vegetative amoebae, and its activity diminished during cell differentiation. The cell-surface bound enzyme was less active than the extracellular enzyme, and its activity decreased twofold during a 6-h starvation period. The enzyme activity of homogenates and 48,000 x g pellets diminished during this period 35 to 40%. The supernatant of a homogenate had a higher deaminase activity than the homogenate itself or its pellet; this suggests the presence of an inhibitor in the particulate fraction. The underlying mechanism for inactivation of folic acid has similar characteristics as that for inactivation of cyclic adenosine monophosphate. PMID:7400095

  11. Folic acid and autism: What do we know?

    PubMed

    Castro, Kamila; Klein, Luciana da Silveira; Baronio, Diego; Gottfried, Carmem; Riesgo, Rudimar; Perry, Ingrid Schweigert

    2014-08-01

    Autism spectrum disorders (ASD) consist in a range of neurodevelopmental conditions that share common features with autism, such as impairments in communication and social interaction, repetitive behaviors, stereotypies, and a limited repertoire of interests and activities. Some studies have reported that folic acid supplementation could be associated with a higher incidence of autism, and therefore, we aimed to conduct a systematic review of studies involving relationships between this molecule and ASD. The MEDLINE database was searched for studies written in English which evaluated the relationship between autism and folate. The initial search yielded 60 potentially relevant articles, of which 11 met the inclusion criteria. The agreement between reviewers was κ = 0.808. The articles included in the present study addressed topics related to the prescription of vitamins, the association between folic acid intake/supplementation during pregnancy and the incidence of autism, food intake, and/or nutrient supplementation in children/adolescents with autism, the evaluation of serum nutrient levels, and nutritional interventions targeting ASD. Regarding our main issue, namely the effect of folic acid supplementation, especially in pregnancy, the few and contradictory studies present inconsistent conclusions. Epidemiological associations are not reproduced in most of the other types of studies. Although some studies have reported lower folate levels in patients with ASD, the effects of folate-enhancing interventions on the clinical symptoms have yet to be confirmed. PMID:25087906

  12. Folic acid in early pregnancy: a public health success story

    PubMed Central

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

    2010-01-01

    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. PMID:20631328

  13. Detection of folic acid protein in human serum using reduced graphene oxide electrodes modified by folic-acid.

    PubMed

    He, Lijie; Wang, Qian; Mandler, Daniel; Li, Musen; Boukherroub, Rabah; Szunerits, Sabine

    2016-01-15

    The detection of disease markers is considered an important step for early diagnosis of cancer. We design in this work a novel electrochemical sensing platform for the sensitive and selective detection of folic acid protein (FP). The platform is fabricated by electrophoretic deposition (EPD) of reduced graphene oxide (rGO) onto a gold electrode and post-functionalization of rGO with folic acid. Upon FP binding, a significant current decrease can be measured using differential pulse voltammetry (DPV). Using this scheme, a detection limit of 1pM is achieved. Importantly, the method also allows the detection of FP in serum being thus an appealing approach for the sensitive detection of biomarkers in clinical samples. PMID:26342582

  14. A relationship between vitamin B sub 12 , folic acid, ascorbic acid, and mercury uptake and methylation

    SciTech Connect

    Zorn, N.E.; Smith, J.T. )

    1990-01-01

    Ingestion of megadoses of certain vitamins appears to influence the in vivo methylation of mercuric chloride in guinea pigs. The addition of megadoses of vitamin B{sub 12} fed either singularly or in combination with folic acid resulted in increased methylmercury concentrations in the liver. Moreover, percent methylmercury levels were significantly increased with B{sub 12} treatment in the liver (B{sub 12} only and B{sub 12}/folic acid) and brain (B{sub 12}/vitamin C). Incorporation of high levels of folic acid into the dietary regime also increased the methylmercury concentration particularly in the liver and hair tissues. The addition of vitamin C in the diet, particularly in combination with B{sub 12} (brain) or folic acid (muscle) resulted in increased methylmercury levels in these tissues and percent methylmercury values with B{sub 12} in the muscle and brain tissue.

  15. [Uncertain effects of folic acid on disorders other than neural-tube defects].

    PubMed

    Verhoef, P; Katan, M B

    2006-07-01

    Periconceptional supplemention with folic acid prevents neural-tube defects in infants. However, contrary to expectations, clinical trials found no beneficial effect of folic acid on the recurrence of cardiovascular disease. Trial evidence on folic acid and cognitive decline or dementia is scarce, though observational studies suggest that high folate intake may prevent these disorders. In contrast, animal studies suggest that high doses of folic acid enhance the growth of existing tumours. However, recent clinical trials failed to show significant effects of folic acid on cancer incidence and mortality. There are also speculations that folic-acid fortification may increase the number of newborns with the thermolabile variant of methylene tetrahydrofolate reductase. There appears to be little evidence that folic-acid supplementation may mask vitamin-B12 deficiency. In view of these controversies, it is unlikely that The Netherlands will mandate folic-acid fortification of staple foods in the near future. Therefore, women who are planning a pregnancy should be urged to take folic-acid supplements. PMID:16875263

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

    NASA Astrophysics Data System (ADS)

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

    2012-09-01

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

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

    PubMed Central

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

    2010-01-01

    The present study investigated the effect of folic acid supplementation on the Notch signaling pathway and cell proliferation in rat embryonic neural stem cells (NSCs). The NSCs were isolated from E14–16 rat brain and grown as neurospheres in serum-free suspension culture. Individual cultures were assigned to one of 3 treatment groups that differed according to the concentration of folic acid in the medium: Control (baseline folic acid concentration of 4 mg/l), low folic acid supplementation (4 mg/l above baseline, Folate-L) and high folic acid supplementation (40 mg/l above baseline, Folate-H). NSCs were identified by their expression of immunoreactive nestin and proliferating cells by incorporation of 5'bromo-2'deoxyuridine. Cell proliferation was also assessed by methyl thiazolyl tetrazolium assay. Notch signaling was analyzed by real-time PCR and western blot analyses of the expression of Notch1 and hairy and enhancer of split 5 (Hes5). Supplementation of NSCs with folic acid increased the mRNA and protein expression levels of Notch1 and Hes5. Folic acid supplementation also stimulated NSC proliferation dose-dependently. Embryonic NSCs respond to folic acid supplementation with increased Notch signaling and cell proliferation. This mechanism may mediate the effects of folic acid supplementation on neurogenesis in the embryonic nervous system. PMID:20838574

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

    PubMed Central

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

    2012-01-01

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

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

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

    ERIC Educational Resources Information Center

    deRosset, Leslie; Mullenix, Amy; Zhang, Lei

    2009-01-01

    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…

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  3. Assessment of Folic Acid Supplementation in Pregnant Women by Estimation of Serum Levels of Tetrahydrofolic Acid, Dihydrofolate Reductase, and Homocysteine

    PubMed Central

    Saxena, Vartika; Mirza, Anissa Atif; Kumari, Ranjeeta; Sharma, Kapil; Bharadwaj, Jyoti

    2016-01-01

    Background. Status of folic acid use in pregnant women of the hilly regions in North India was little known. This study was carried out to assess the folic acid use and estimate folate metabolites in pregnant women of this region. Materials and Methods. This cross-sectional study is comprised of 76 pregnant women, whose folic acid supplementation was assessed by a questionnaire and serum levels of homocysteine, tetrahydrofolic acid (THFA), and dihydrofolate reductase (DHFR) were estimated using Enzyme Linked Immunoassays. Results. The study data revealed awareness of folic acid use during pregnancy was present in 46.1% and 23.7% were taking folic acid supplements. The study depicted that there was no statistically significant difference between serum levels of THFA and DHFR in pregnant women with and without folic acid supplements (p = 0.790). Hyperhomocysteinemia was present in 15.78% of the participants. Conclusion. Less awareness about folic acid supplementation and low use of folic acid by pregnant women were observed in this region. Sufficient dietary ingestion may suffice for the escalated requirements in pregnancy, but since this cannot be ensured, hence folic acid supplementation should be made as an integral part of education and reproductive health programs for its better metabolic use, growth, and development of fetus. PMID:27064332

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

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  6. The risk of menstrual abnormalities after preconceptional use of folic acid or a folic acid-containing multivitamin in Chinese women.

    PubMed

    Shen, Lianlian; Chu, Zhiping; Yang, Jian; Wang, Yubang

    2016-01-01

    The associations of preconceptional folic acid use with menstruation-related changes were examined by a retrospective study through 219 questionnaires. The kind of folic acid (alone or with other vitamins), the using time and frequency, the menstrual regularity, the cycle length before and after use, and other menstruation-related changes after use were obtained. Two hundred of 219 participants were users, and menstruation-related changes occurred in 32 women, with abnormalities of involvement being longer cycles (increase of 3-20 days, 7.7 ± 4.8 days), shorter cycles (decrease of 3-7 days, 5.7 ± 2.3 days), irregular cycles, less blood loss, bleeding or spotting between cycles, and algomenorrhea. Seventeen women stopped using folic acid or folic acid-containing multivitamin, and sixteen of the seventeen women experienced at least one menstruation before conception. Fifteen of sixteen women found complete recovery, indicating the high possibility that these changes were attributed to the use of folic acid or folic acid-containing multivitamin. PMID:26654378

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

    PubMed Central

    Hassan, Kamal

    2015-01-01

    Background Most of the folic acid sources are rich also in potassium. Patients with chronic kidney disease (CKD) usually receive a low potassium diet. We investigated the possibility of an association between low potassium diet and folic acid deficiency. Methods In total, 128 CKD patients participated in this cross-sectional study. Sixty-four patients with CKD grades 1 and 2 were on an unrestricted potassium diet when enrolled in the study, and 64 patients with CKD grades 3 and 4 had received instructions to restrict their intake of potassium at least 6 months before enrollment in the study. Subjects were evaluated for daily intake of folic acid (DIFA), daily intake of potassium (DIK), and serum folic acid levels (SFA). Results DIFA correlated with the estimated glomerular filtration rate, the DIK, and the SFA (P<0.001). SFA correlated with the estimated glomerular filtration rate (P<0.001). Mean DIFA and mean SFA were lower among patients with CKD grades 3 and 4 than among those with CKD grades 1 and 2 (P<0.001). The mean DIFA in patients with folic acid deficiency was lower than that in those with SFA ≥7.1 nmol/L (P<0.001). There was lower SFA and threefold greater frequency of folic acid deficiency among patients with CKD grades 3 and 4 who had received instructions to restrict their intake of potassium than among patients with CKD grades 1 and 2 who were on an unrestricted potassium diet. Conclusion A potassium-restricted diet offered to patients with CKD grades 3 and 4 may be associated with folic acid deficiency. Serum levels of folic acid should be investigated before starting potassium restriction in patients with CKD grades 3 and 4, in order to identify individuals with folic acid deficiency or with marginal serum levels who should receive folic acid replacement therapy. PMID:26056461

  8. Evaluation of the Dutch general exemption level for voluntary fortification with folic acid

    PubMed Central

    Verkaik-Kloosterman, Janneke; Beukers, Marja; Buurma-Rethans, Elly; Verhagen, Hans; C Ocké, Marga

    2012-01-01

    Introduction Fortification with folic acid was prohibited in the Netherlands. Since 2007, a general exemption is given to fortify with folic acid up until a maximum level of 100 µg/100 kcal. This maximum level was based on a calculation model and data of adults only. The model requires parameters on intake (diet, supplements, energy) and on the proportion of energy that may be fortified. This study aimed to evaluate the model parameters considering the changing fortification market. In addition, the risk of young children exceeding the UL for folic acid was studied. Methods Folic acid fortified foods present on the Dutch market were identified in product databases and by a supermarket inventory. Together with data of the Dutch National Consumption Survey-Young Children (2005/2006) these inventory results were used to re-estimate the model parameters. Habitual folic acid intake of young children was estimated and compared to the UL for several realistic fortification scenarios. Results Folic acid fortified foods were identified in seven different food groups. In up to 10% of the population, the proportion of energy intake of folic acid fortified foods exceeded 10% – the original model parameter. The folic acid intake from food supplements was about 100 µg/day, which is lower than the intake assumed as the original model parameter (300 µg). In the scenarios representing the current market situation, a small proportion (<5%) of the children exceeded the UL. Conclusion The maximum fortification level of 100 µg/100 kcal is sufficiently protective for children in the current market situation. In the precautionary model to estimate the maximum fortification levels, subjects with high intakes of folic acid from food and supplements, and high energy intakes are protected from too high folic acid intakes. Combinations of high intakes are low in this population. The maximum levels should be monitored and revised with increasing fortification and supplementation practices. PMID:22481899

  9. Association Between Adherence to Folic Acid Supplements and Serum Folate, and Plasma Homocysteine Among Hemodialysis Patients

    PubMed Central

    Leung, June; Dwyer, Johanna; Hibberd, Patricia; Jacques, Paul; Rand, William; Rocco, Michael V.

    2010-01-01

    Objective To examine the relationship between adherence to prescribed folic acid supplements and folic acid intake, serum folate and plasma homocysteine in hemodialysis patients. The effects of change in adherence patterns from enrollment to one year later on changes in these same measures were also assessed. Design Secondary data analysis Participants Eighty six hemodialysis patients who participated in the Hemodialysis (HEMO) Study’s Homocysteine ancillary study. Main Outcome Measures Folic acid supplement intake, serum folate and plasma homocysteine. Results Eighty-eight percent of patients at enrollment and 91% one year later were adherent to prescribed folic acid supplements. Non-adherers had lower intakes of folic acid at both enrollment and one year later and lower serum folate levels at enrollment. Percent change was significantly different between the 3 adherence change groups for folic acid intake (p=0.001) and plasma homocysteine (p<0.001) from enrollment to one year later. The non-adherent group at enrollment had the lowest intakes and serum folate levels, and the highest plasma homocysteine levels. When they became adherent one year later, they had the greatest change in folic acid intake (5461%; p=0.03), coupled with a 69% increase in serum folate (p=0.04) and a 29% decrease in plasma homocysteine (p=0.03). Conclusions Hemodialysis patients who were non-adherent to folic acid supplement prescriptions had low folic acid intakes, low serum folates and high homocysteine levels. When their adherence improved, folic acid intakes rose, serum folates increased and plasma homocysteine levels decreased, although mild hyperhomocysteinemia persisted. PMID:20650653

  10. Curcumin and folic acid abrogated methotrexate induced vascular endothelial dysfunction.

    PubMed

    Sankrityayan, Himanshu; Majumdar, Anuradha S

    2016-01-01

    Methotrexate, an antifolate drug widely used in rheumatoid arthritis, psoriasis, and cancer, is known to cause vascular endothelial dysfunction by causing hyperhomocysteinemia, direct injury to endothelium or by increasing the oxidative stress (raising levels of 7,8-dihydrobiopterin). Curcumin is a naturally occurring polyphenol with strong antioxidant and anti-inflammatory action and therapeutic spectra similar to that of methotrexate. This study was performed to evaluate the effects of curcumin on methotrexate induced vascular endothelial dysfunction and also compare its effect with that produced by folic acid (0.072 μg·g(-1)·day(-1), p.o., 2 weeks) per se and in combination. Male Wistar rats were exposed to methotrexate (0.35 mg·kg(-1)·day(-1), i.p.) for 2 weeks to induce endothelial dysfunction. Methotrexate exposure led to shedding of endothelium, decreased vascular reactivity, increased oxidative stress, decreased serum nitrite levels, and increase in aortic collagen deposition. Curcumin (200 mg·kg(-1)·day(-1) and 400 mg·kg(-1)·day(-1), p.o.) for 4 weeks prevented the increase in oxidative stress, decrease in serum nitrite, aortic collagen deposition, and also vascular reactivity. The effects were comparable with those produced by folic acid therapy. The study shows that curcumin, when concomitantly administered with methotrexate, abrogated its vascular side effects by preventing an increase in oxidative stress and abating any reduction in physiological nitric oxide levels. PMID:26571019

  11. Folic acid fortification of grain: an economic analysis.

    PubMed Central

    Romano, P S; Waitzman, N J; Scheffler, R M; Pi, R D

    1995-01-01

    OBJECTIVES. The purpose of this study was to compare the economic costs and benefits of fortifying grain with folic acid to prevent neural tube defects. METHODS. A cost-benefit analysis based on the US population, using the human capital approach to estimate the costs associated with preventable neural tube defects, was conducted. RESULTS. Under a range of assumptions about discount rates, baseline folate intake, the effectiveness of folate in preventing neural tube defects, the threshold dose that minimizes risk, and the cost of surveillance, fortification would likely yield a net economic benefit. The best estimate of this benefit is $94 million with low-level (140 micrograms [mcg] per 100 g grain) fortification and $252 million with high-level (350 mcg/100 g) fortification. The benefit-to-cost ratio is estimated at 4.3:1 for low-level and 6.1:1 for high-level fortification. CONCLUSIONS. By averting costly birth defects, folic acid fortification of grain in the United States may yield a substantial economic benefit. We may have underestimated net benefits because of unmeasured costs of neural tube defects and unmeasured benefits of higher folate intake. We may have overestimated net benefits if the cost of neurologic sequelae related to delayed diagnosis of vitamin B12 deficiency exceeds our projection. PMID:7733427

  12. Folic acid and the methylation of homocysteine by Bacillus subtilis

    PubMed Central

    Salem, A. R.; Pattison, J. R.; Foster, M. A.

    1972-01-01

    1. Cell-free extracts of Bacillus subtilis synthesize methionine from serine and homocysteine without added folate. The endogenous folate may be replaced by tetrahydropteroyltriglutamate or an extract of heated Escherichia coli for the overall C1 transfer, but tetrahydropteroylmonoglutamate is relatively inactive. 2. Extracts of B. subtilis contain serine transhydroxymethylase and 5,10-methylenetetrahydrofolate reductase, which are non-specific with respect to the glutamate content of the folate substrates. Methyl transfer to homocysteine requires a polyglutamate folate as methyl donor. These properties are not affected by growth of the organism with added vitamin B12. 3. The synthesis of methionine from 5-methyltetrahydropteroyltriglutamate and homocysteine has the characteristics of the cobalamin-independent reaction of E. coli. No evidence for a cobalamin-dependent transmethylation was obtained. 4. S-Adenosylmethionine was not a significant precursor of the methyl group of methionine with cell-free extracts, neither was S-adenosylmethionine generated by methylation of S-adenosylhomocysteine by 5-methyltetrahydrofolate. 5. A procedure for the isolation and analysis of folic acid derivatives from natural sources is described. 6. The folates isolated from lysozyme extracts of B. subtilis are sensitive to folic acid conjugase. One has been identified as 5-formyltetrahydropteroyltriglutamate; the other is possibly a diglutamate folate. 7. A sequence is proposed for methionine biosynthesis in B. subtilis in which methyl groups are generated from serine and transferred to homocysteine by means of a cobalamin-independent pathway mediated by conjugated folate coenzymes. PMID:4627401

  13. Malaria in the Era of Food Fortification With Folic Acid.

    PubMed

    Nzila, Alexis; Okombo, John; Hyde, John

    2016-06-01

    Food fortified with folic acid has been available for consumption in North America for over a decade. This strategy has led to an increase in folate levels in the general population and, more importantly, a significant decrease in the incidence of neural tube defects. However, this increase in folate intake has been associated with a greater risk of cancer disease. Many African countries are now embracing this concept; however, because folate promotes malaria parasite division, as it does in cancer cells, there is a possibility of malaria exacerbation if folate intake is increased. A precedent for such a concern is the now compelling evidence showing that an increase in iron intake can lead to a higher malaria risk; as a result, mass administration of iron in malaria-endemic areas is not recommended. In this article, we review work on the effect of folate on malaria parasites. Although this topic has received little research attention, the available data suggest that the increase in folate concentration could be associated with an increase in malaria infection. Thus, the introduction of food fortification with folic acid in malaria-endemic areas should be attended by precautionary programs to monitor the risk of malaria. PMID:26944505

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

    PubMed

    Ding, Xuzhe; Yao, Ping

    2013-07-01

    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

  15. Folic acid supplementation for pregnant women and those planning pregnancy: 2015 update.

    PubMed

    Chitayat, David; Matsui, Doreen; Amitai, Yona; Kennedy, Deborah; Vohra, Sunita; Rieder, Michael; Koren, Gideon

    2016-02-01

    During the last decade critical new information has been published pertaining to folic acid supplementation in the prevention of neural tube defects (NTDs) and other folic acid-sensitive congenital malformations. These new data have important implications for women, their families, and health care professionals. We performed a review looking for the optimal dosage of folic acid that should be given to women of reproductive age who are planning or not avoiding conception to propose updated guidelines and thus help health care providers and patients. In addition to fortification of dietary staples with folic acid, women of reproductive age should supplement before conception with 0.4-1.0?mg of folic acid daily as part of their multivitamins. In the United States all enriched rice is also fortified with folic acid at 0.7?mg per pound of raw rice. However, this is not the case in many countries, and it has been estimated that only 1% of industrially milled rice is fortified with folic acid. In countries where rice is the main staple (eg, China), this does not allow effective folate fortification. Whereas the incidence of NTDs is around 1/1000 in the United States, it is 3- to 5-fold higher in Northern China and 3-fold higher in India. A recent population-based US study estimated that the reduction in NTD rates by folic acid is more modest than previously predicted. The potential of NTD prevention by folic acid is underutilized due to low adherence with folic acid supplementation, and calls for revising the policy of supplementation have been raised. We identified groups of women of reproductive age who may benefit from higher daily doses of folic acid, and this should be considered in current practice. These include women who have had previous pregnancies with NTDs, those who did not plan their pregnancy and hence did not supplement, and women with low intake or impaired adherence to daily folic acid supplementation. In addition, women with known genetic variations in the folate metabolic cycle, those exposed to medications with antifolate effects, smokers, diabetics, and the obese may benefit from higher doses of folic acid daily during the first trimester. PMID:26272218

  16. Folic acid supplementation for pregnant women and those planning pregnancy: 2015 update

    PubMed Central

    Chitayat, David; Matsui, Doreen; Amitai, Yona; Kennedy, Deborah; Vohra, Sunita; Rieder, Michael

    2015-01-01

    Abstract During the last decade critical new information has been published pertaining to folic acid supplementation in the prevention of neural tube defects (NTDs) and other folic acid–sensitive congenital malformations. These new data have important implications for women, their families, and health care professionals. We performed a review looking for the optimal dosage of folic acid that should be given to women of reproductive age who are planning or not avoiding conception to propose updated guidelines and thus help health care providers and patients. In addition to fortification of dietary staples with folic acid, women of reproductive age should supplement before conception with 0.4‐1.0 mg of folic acid daily as part of their multivitamins. In the United States all enriched rice is also fortified with folic acid at 0.7 mg per pound of raw rice. However, this is not the case in many countries, and it has been estimated that only 1% of industrially milled rice is fortified with folic acid. In countries where rice is the main staple (eg, China), this does not allow effective folate fortification. Whereas the incidence of NTDs is around 1/1000 in the United States, it is 3‐ to 5‐fold higher in Northern China and 3‐fold higher in India. A recent population‐based US study estimated that the reduction in NTD rates by folic acid is more modest than previously predicted. The potential of NTD prevention by folic acid is underutilized due to low adherence with folic acid supplementation, and calls for revising the policy of supplementation have been raised. We identified groups of women of reproductive age who may benefit from higher daily doses of folic acid, and this should be considered in current practice. These include women who have had previous pregnancies with NTDs, those who did not plan their pregnancy and hence did not supplement, and women with low intake or impaired adherence to daily folic acid supplementation. In addition, women with known genetic variations in the folate metabolic cycle, those exposed to medications with antifolate effects, smokers, diabetics, and the obese may benefit from higher doses of folic acid daily during the first trimester. PMID:26272218

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

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

    2014-01-01

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

  19. Folic acid for the prevention of neural tube defects: the Danish experience.

    PubMed

    Olsen, Sjurdur F; Knudsen, Vibeke Kildegaard

    2008-06-01

    Evidence from controlled trials suggests that ingestion of 0.4 mg of folic acid per day in the periconceptional period is effective in preventing neural tube defects (NTD). For this reason, most countries recommend that women planning pregnancy take folic acid supplements in the periconceptional period, and some countries even fortify stable foods with folic acid. Denmark exemplifies a country with a relatively conservative attitude with respect to taking action in these matters. In 1999, a national information campaign was launched that recommended women planning pregnancy take 0.4 mg of folic acid periconceptionally, but with the moderation that women who eat a healthy diet do not need to take folic acid supplement. The campaign was repeated during 2001. The results of the latter campaign were evaluated by using data from a national survey among pregnant women conducted simultaneously with the campaign by the Danish National Birth Cohort. An increase in the proportion of folic acid users took place concomitantly with the launching of the information events, but the increase was limited. Among women who did not plan their pregnancy, a small proportion had taken folic acid supplements periconceptionally, and this proportion did not change concomitantly with the campaign. Young age and low education were factors associated with low likelihood of taking folic acid. It seems that different and more efficient actions are needed if a more substantial proportion of Danish women and their fetuses are going to benefit from the knowledge that folic acid supplementation in the periconceptional period can prevent NTD. PMID:18709894

  20. Women’s Awareness of Periconceptional Use of Folic Acid Before and After Their Antenatal Visits

    PubMed Central

    Maher, Mark; Keriakos, Remon

    2014-01-01

    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. PMID:24817820

  1. High folic acid intake reduces natural killer cell cytotoxicity in aged mice.

    PubMed

    Sawaengsri, Hathairat; Wang, Junpeng; Reginaldo, Christina; Steluti, Josiane; Wu, Dayong; Meydani, Simin Nikbin; Selhub, Jacob; Paul, Ligi

    2016-04-01

    Presence of unmetabolized folic acid in plasma, which is indicative of folic acid intake beyond the metabolic capacity of the body, is associated with reduced natural killer (NK) cell cytotoxicity in postmenopausal women ≥50years. NK cells are cytotoxic lymphocytes that are part of the innate immune system critical for surveillance and defense against virus-infected and cancer cells. We determined if a high folic acid diet can result in reduced NK cell cytotoxicity in an aged mouse model. Female C57BL/6 mice (16-month-old) were fed an AIN-93M diet with the recommended daily allowance (1× RDA, control) or 20× RDA (high) folic acid for 3months. NK cytotoxicity was lower in splenocytes from mice fed a high folic acid diet when compared to mice on control diet (P<.04). The lower NK cell cytotoxicity in high folic acid fed mice could be due to their lower mature cytotoxic/naïve NK cell ratio (P=.03) when compared to the control mice. Splenocytes from mice on high folic acid diet produced less interleukin (IL)-10 when stimulated with lipopolysaccharide (P<.05). The difference in NK cell cytotoxicity between dietary groups was abolished when the splenocytes were supplemented with exogenous IL-10 prior to assessment of the NK cytotoxicity, suggesting that the reduced NK cell cytotoxicity of the high folic acid group was at least partially due to reduced IL-10 production. This study demonstrates a causal relationship between high folic acid intake and reduced NK cell cytotoxicity and provides some insights into the potential mechanisms behind this relationship. PMID:27012626

  2. [Neural tube defects and folic acid: a historical overview of a highly successful preventive intervention].

    PubMed

    Vásquez, Adriana Ordoñez; Suarez-Obando, Fernando

    2015-12-01

    This article gives a broad overview of part of the historical evolution of medical knowledge about neural tube defects (NTD) and the discovery of vitamin B9 or folic acid, as well as some relevant research events that, over the course of several centuries, defined the relationships between the understanding of central nervous system embryology, the discovery of the vitamin, the correlation between folic acid and cell proliferation and lastly the development of preventive measures for this type of defects. This narrative allows us to examine historically relevant concepts underlying clinical actions with a populational impact that prevent NTDs via folic acid consumption prior to conception. PMID:25650704

  3. Folic acid induces salicylic acid-dependent immunity in Arabidopsis and enhances susceptibility to Alternaria brassicicola.

    PubMed

    Wittek, Finni; Kanawati, Basem; Wenig, Marion; Hoffmann, Thomas; Franz-Oberdorf, Katrin; Schwab, Wilfried; Schmitt-Kopplin, Philippe; Vlot, A Corina

    2015-08-01

    Folates are essential for one-carbon transfer reactions in all organisms and contribute, for example, to de novo DNA synthesis. Here, we detected the folate precursors 7,8-dihydropteroate (DHP) and 4-amino-4-deoxychorismate (ADC) in extracts from Arabidopsis thaliana plants by Fourier transform ion cyclotron resonance-mass spectrometry. The accumulation of DHP, but not ADC, was induced after infection of plants with Pseudomonas syringae delivering the effector protein AvrRpm1. Application of folic acid or the DHP precursor 7,8-dihydroneopterin (DHN) enhanced resistance in Arabidopsis to P. syringae and elevated the transcript accumulation of the salicylic acid (SA) marker gene pathogenesis-related1 in both the treated and systemic untreated leaves. DHN- and folic acid-induced systemic resistance was dependent on SA biosynthesis and signalling. Similar to SA, folic acid application locally enhanced Arabidopsis susceptibility to the necrotrophic fungus Alternaria brassicicola. Together, the data associate the folic acid pathway with innate immunity in Arabidopsis, simultaneously activating local and systemic SA-dependent resistance to P. syringae and suppressing local resistance to A. brassicicola. PMID:25348251

  4. Determination of the active portion of the folic acid molecule in cellular slime mold chemotaxis.

    PubMed Central

    Pan, P; Hall, E M; Bonner, J T

    1975-01-01

    From earlier work it is known that folic acid attracts the amoebae of various species of cellular slime molds (11). Here we have tested a wide variety of pteridines, pyrimidines, and pyrazines to determine what part of the folic acid molecule is chemotactically active. It was shown that the activity lies in the pteridine ring itself. Furthermore, the cell-free supernatants of slime mold amoebae contain an enzyme that renders pterin and folic acid chemotactically inactive, which apparently increases the chemotactic sensitivity of the amoebae to those compounds. Despite the fact that slime mold amoebae secrete small amounts of folic acid-related compounds, there is no evidence that folates are acrasins; rather it is postulated that attraction to folates may be a food-seeking device for the amoebae which prey on folate-secreting bacteria in the soil. PMID:164431

  5. Folic acid for the prevention of neural tube defects. American Academy of Pediatrics. Committee on Genetics.

    PubMed

    1999-08-01

    The American Academy of Pediatrics endorses the US Public Health Service (USPHS) recommendation that all women capable of becoming pregnant consume 400 microgram of folic acid daily to prevent neural tube defects (NTDs). Studies have demonstrated that periconceptional folic acid supplementation can prevent 50% or more of NTDs such as spina bifida and anencephaly. For women who have previously had an NTD-affected pregnancy, the Centers for Disease Control and Prevention (CDC) recommends increasing the intake of folic acid to 4000 microgram per day beginning at least 1 month before conception and continuing through the first trimester. Implementation of these recommendations is essential for the primary prevention of these serious and disabling birth defects. Because fewer than 1 in 3 women consume the amount of folic acid recommended by the USPHS, the Academy notes that the prevention of NTDs depends on an urgent and effective campaign to close this prevention gap. PMID:10429019

  6. Rhodamine-6G can photosensitize folic acid decomposition through electron transfer

    NASA Astrophysics Data System (ADS)

    Hirakawa, Kazutaka; Ito, Hiroki

    2015-05-01

    Rhodamine-6G photosensitized folic acid decomposition in aqueous solution, and its quantum yield in the presence of 10 ?M folic acid was 9.9 10-6. A possible mechanism of this photodecomposition is direct oxidation through an electron transfer from folic acid to rhodamine-6G. The fluorescence lifetime of rhodamine-6G was slightly decreased by folic acid, suggesting electron transfer in the excited singlet state of rhodamine-6G. The quenching rate coefficient estimated from the Stern-Volmer plot of the fluorescence quenching supported that this electron transfer proceeds as a diffusion-controlled reaction. The quantum yields of the electron transfer and the following reaction could be determined.

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

    PubMed

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

    2008-10-01

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

  8. Folic Acid for Moms-To-Be Not as Effective as Thought?

    MedlinePlus

    ... html Folic Acid for Moms-to-Be Not as Effective as Thought? Study authors stress women should still take ... protected against the risk of certain birth defects as much as experts thought it would, a large, ...

  9. Encapsulation of folic acid in food hydrocolloids through nanospray drying and electrospraying for nutraceutical applications.

    PubMed

    Pérez-Masiá, Rocío; López-Nicolás, Rubén; Periago, Maria Jesús; Ros, Gaspar; Lagaron, Jose M; López-Rubio, Amparo

    2015-02-01

    In this work, two different technologies (electrospraying and nanospray drying) were evaluated for the encapsulation of folic acid using both a whey protein concentrate (WPC) matrix and a commercial resistant starch. The morphology of the capsules, molecular organization of the matrices upon encapsulation, encapsulation efficiency, and stability of the folic acid within the capsules under different storage conditions and upon thermal exposure were studied. Results showed that spherical nano-, submicro- and microcapsules were obtained through both techniques, although electrospraying led to smaller capsule sizes and to an enhanced control over their size distribution. Greater encapsulation efficiency was observed using WPC as encapsulating matrix, probably related to interactions between the protein and folic acid which favoured the incorporation of the bioactive. The best results in terms of bioactive stabilization in the different conditions assayed were also obtained for the WPC capsules, although both materials and encapsulation techniques led to improved folic acid stability, especially under dry conditions. PMID:25172691

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  11. The folic acid requirements of starting broiler chicks fed diets based on practical ingredients. 1. Interrelationships with dietary choline.

    PubMed

    Ryu, K S; Roberson, K D; Pesti, G M; Eitenmiller, R R

    1995-09-01

    Five experiments were conducted to evaluate the effect of dietary supplemental folic acid in starting broiler chick diets. In the first two experiments, basal diets based on corn and soybean meal contained 10 micrograms/kg vitamin B12 but no supplemental methionine or choline. Chicks showed curvilinear responses to folic acid supplementation with maximum growth and feed efficiencies from 1.45 mg/kg diet. The liver folic acid response was also curvilinear but reached a plateau at 1.70 mg folic acid/kg diet. The basal diet for three additional experiments contained soybean meal that had been washed with methanol to remove most of the choline. The basal diet contained only 750 mg/kg choline. Chicks exhibited a larger growth response to folic acid at low choline levels as evidenced by a significant folic acid by choline interaction. Choline and folic acid both increased tibia length and width. Folic acid supplementation increased but then decreased valgus deformity. Choline chloride supplementation also decreased the incidences of valgus and varus deformities and decreased bone ash, but increased the incidence of tibial dyschondroplasia. It is concluded that chicks fed practical ingredient-based diets require 1.3 mg folic acid/kg diet with low levels of choline, but only 1.2 mg folic acid/kg when choline is offered near the NRC recommended level of 1,300 mg/kg of choline. PMID:7501589

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

    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. PMID:23658501

  14. Folic Acid Supplementation in Pregnancy and the Risk of Pre-Eclampsia—A Cohort Study

    PubMed Central

    Wen, Shi Wu; Guo, Yanfang; Rodger, Marc; White, Ruth Rennicks; Yang, Qiuying; Smith, Graeme N.; Perkins, Sherry L.; Walker, Mark C.

    2016-01-01

    This prospective cohort study designed to assess the effect of folic acid supplementation in pregnancy on the risk of preeclampsia (PE) took place in Ottawa, ON and Kingston, ON, Canada, from September 1, 2002 to August 31, 2008. Pregnant women, less than 20 weeks gestational age were recruited and delivered in the Ottawa region and the Kingston General Hospital. Demographic characteristics of the study participants and the patterns of supplementation of folic acid were described and occurrence of PE between women with folic acid supplementation during pregnancy and women without were compared. Multiple logistic regression was used in the estimation of the independent effect of supplementation of folic acid. Additional analyses assessing the effect of low RBC and serum folate and dose-response relationship were performed. Analyses were performed in all study participants, and then in high risk and low risk sub-groups, respectively. A total of 7,669 participants were included in the final analysis. Ninety five percent of the study participants were taking folic acid supplementation in early second trimester. The rate of PE was lower in the supplementation group than in the no supplementation group, and the difference was statistically significant in high risk women. Similar patterns of associations were observed in analysis by RBC and serum folate levels and in dose-response analysis. Folic acid supplementation in pregnancy may reduce PE risk in pregnant women, especially in those women with increased risk of developing PE. PMID:26901463

  15. [The effect of folic acid fortification on the reduction of neural tube defects].

    PubMed

    Santos, Leonor Maria Pacheco; Pereira, Michelle Zanon

    2007-01-01

    Neural tube defects are congenital malformations that occur during initial fetal development, leading to anencephaly and spina bifida; folic acid deficiency is the most important risk factor identified to date. Brazil has one of the world's highest neural tube defect rates. Food consumption surveys among pregnant Brazilian women showed a high rate of inadequate folic acid intake (< 0.6 mg/day). In 2004, the National Health Surveillance Agency (ANVISA) mandated the fortification of corn meal and wheat flour with folic acid (0.15 mg/100g). The National Family Budget Survey estimated the average amount of bread/flour products available in households as 106.1g/day (contributing with 0.16 mg folic acid/day). However, while in the South of the country the supply was 144 g/day, in the North and Central West it barely reached 70 g/day. Folic acid food fortification is mandatory in some 40 countries, but only four have assessed this strategy. The existing studies have all shown a significant impact, ranging from 19 to 78%. Folic acid fortification is an undeniably important intervention for primary prevention, and neural tube defects can now be considered a preventable epidemic. PMID:17187100

  16. Development of electrochemical folic acid sensor based on hydroxyapatite nanoparticles

    NASA Astrophysics Data System (ADS)

    Kanchana, P.; Sekar, C.

    2015-02-01

    We report the synthesis of hydroxyapatite (HA) nanoparticles (NPs) by a simple microwave irradiation method and its application as sensing element for the precise determination of folic acid (FA) by electrochemical method. The structure and composition of the HA NPs characterized using XRD, FTIR, Raman and XPS. SEM and EDX studies confirmed the formation of elongated spherical shaped HA NPs with an average particle size of about 34 nm. The HA NPs thin film on glassy carbon electrode (GCE) were deposited by drop casting method. Electrocatalytic behavior of FA in the physiological pH 7.0 was investigated by cyclic voltammetry (CV), linear sweep voltammetry (LSV) and chronoamperometry. The fabricated HA/GCE exhibited a linear calibration plot over a wide FA concentration ranging from 1.0 × 10-7 to 3.5 × 10-4 M with the detection limit of 75 nM. In addition, the HA NPs modified GCE showed good selectivity toward the determination of FA even in the presence of a 100-fold excess of ascorbic acid (AA) and 1000-fold excess of other common interferents. The fabricated biosensor exhibits good sensitivity and stability, and was successfully applied for the determination of FA in pharmaceutical samples.

  17. Characteristics of U.S. Adults with Usual Daily Folic Acid Intake above the Tolerable Upper Intake Level: National Health and Nutrition Examination Survey, 2003-2010.

    PubMed

    Orozco, Angela M; Yeung, Lorraine F; Guo, Jing; Carriquiry, Alicia; Berry, Robert J

    2016-01-01

    The Food and Drug Administration mandated that by 1998, all enriched cereal grain products (ECGP) be fortified with folic acid in order to prevent the occurrence of neural tube defects. The Institute of Medicine established the tolerable upper intake level (UL) for folic acid (1000 µg/day for adults) in 1998. We characterized U.S. adults with usual daily folic acid intake exceeding the UL. Using NHANES 2003-2010 data, we estimated the percentage of 18,321 non-pregnant adults with usual daily folic acid intake exceeding the UL, and among them, we calculated the weighted percentage by sex, age, race/ethnicity, sources of folic acid intake, supplement use and median usual daily folic acid intakes. Overall, 2.7% (standard error 0.6%) of participants had usual daily intake exceeding the UL for folic acid; 62.2% were women; 86.3% were non-Hispanic whites; and 98.5% took supplements containing folic acid. When stratified by sex and age groups among those with usual daily folic acid intake exceeding the UL, 20.8% were women aged 19-39 years. Those with usual daily intake exceeding the folic acid UL were more likely to be female, non-Hispanic white, supplement users or to have at least one chronic medical condition compared to those not exceeding the folic acid UL. Among those with usual daily folic acid intake exceeding the UL who also took supplements, 86.6% took on average >400 µg of folic acid/day from supplements. Everyone with usual daily folic acid intake exceeding the UL consumed folic acid from multiple sources. No one in our study population had usual daily folic acid intake exceeding the UL through consumption of mandatorily-fortified enriched cereal grain products alone. Voluntary consumption of supplements containing folic acid is the main factor associated with usual daily intake exceeding the folic acid UL. PMID:27043623

  18. Characteristics of U.S. Adults with Usual Daily Folic Acid Intake above the Tolerable Upper Intake Level: National Health and Nutrition Examination Survey, 2003–2010

    PubMed Central

    Orozco, Angela M.; Yeung, Lorraine F.; Guo, Jing; Carriquiry, Alicia; Berry, Robert J.

    2016-01-01

    The Food and Drug Administration mandated that by 1998, all enriched cereal grain products (ECGP) be fortified with folic acid in order to prevent the occurrence of neural tube defects. The Institute of Medicine established the tolerable upper intake level (UL) for folic acid (1000 µg/day for adults) in 1998. We characterized U.S. adults with usual daily folic acid intake exceeding the UL. Using NHANES 2003–2010 data, we estimated the percentage of 18,321 non-pregnant adults with usual daily folic acid intake exceeding the UL, and among them, we calculated the weighted percentage by sex, age, race/ethnicity, sources of folic acid intake, supplement use and median usual daily folic acid intakes. Overall, 2.7% (standard error 0.6%) of participants had usual daily intake exceeding the UL for folic acid; 62.2% were women; 86.3% were non-Hispanic whites; and 98.5% took supplements containing folic acid. When stratified by sex and age groups among those with usual daily folic acid intake exceeding the UL, 20.8% were women aged 19–39 years. Those with usual daily intake exceeding the folic acid UL were more likely to be female, non-Hispanic white, supplement users or to have at least one chronic medical condition compared to those not exceeding the folic acid UL. Among those with usual daily folic acid intake exceeding the UL who also took supplements, 86.6% took on average >400 µg of folic acid/day from supplements. Everyone with usual daily folic acid intake exceeding the UL consumed folic acid from multiple sources. No one in our study population had usual daily folic acid intake exceeding the UL through consumption of mandatorily-fortified enriched cereal grain products alone. Voluntary consumption of supplements containing folic acid is the main factor associated with usual daily intake exceeding the folic acid UL. PMID:27043623

  19. The folic acid requirements of starting broiler chicks fed diets based on practical ingredients. 2. Interrelationships with dietary methionine.

    PubMed

    Ryu, K S; Pesti, G M; Roberson, K D; Edwards, H M; Eitenmiller, R R

    1995-09-01

    Two experiments were conducted to determine the effects of dietary supplemental folic acid and methionine on the performance of starting broiler chicks for 18 d. Four levels of dietary folic acid (.24, .54, 1.14, and 2.34 mg/kg) and four levels of dietary methionine (.45, .53, .61, and .69%) were fed in a factorial design. There were three replicates of eight chicks each per each treatment. The basal diet was based on corn, isolated soybean protein, meat and bone meal, and fish meal. It contained adequate amounts of all nutrients except methionine and folic acid. Increased growth was observed in chicks fed the basal diet supplemented with either folic acid or methionine. Total dietary folic acid and methionine plus cysteine requirements for maximum growth were estimated to be 1.80 mg/kg and .85% in Experiment 1 and 1.47 mg/kg and .87% in Experiment 2, respectively. There were interactions between dietary folic acid and methionine on weight gain in both experiments. Chicks fed the diet containing 2.34 mg folic acid/kg tended to have depressed growth, as in previous experiments. There was a significant linear feed conversion response to folic acid in Experiment 1 and to methionine in Experiment 2. There were both linear and quadratic liver folic acid responses to dietary folic acid in both experiments. There was no indication that dietary methionine had any effect on liver folic acid content. No differences in bone ash, hemoglobin, hematocrit, or incidence of tibial dyschondroplasia were detected due to methionine or folic acid supplementation. PMID:7501590

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

    PubMed Central

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

    1995-01-01

    OBJECTIVES. This article uses folic acid as an example to illustrate some of the complex issues and general principles that emerge when evaluating fortification of the food supply as one possible means to address a public health recommendation. METHODS. Distributions of current daily folate intakes from conventional foods and dietary supplements were estimated. Intakes that might result from fortification of cereal-grain products and ready-to-eat cereals at various levels for eight age-gender groups were also estimated by using the US Department of Agriculture's 1987-1988 Nationwide Food Consumption Survey. RESULTS. The results illustrate that fortification of the US food supply tends to increase folate intakes of consumers at the high end of the intake distribution curves in the general population to a greater extent than it affects consumers at the low end of the intake distribution curves in the target population. CONCLUSIONS. The effectiveness of food fortification options for a target population and the safety for the general population impose conflicting challenges that must be considered concurrently when making decisions about fortifying the US food supply. Images FIGURE 4 FIGURE 5 PMID:7733426

  1. A review of European guidelines on periconceptional folic acid supplementation.

    PubMed

    Cawley, S; Mullaney, L; McKeating, A; Farren, M; McCartney, D; Turner, M J

    2016-02-01

    Strong evidence that folic acid (FA) prevents the majority of cases of neural tube defects (NTDs) has led to national organisations developing guidelines for women concerning periconceptional supplementation. In Europe, there is evidence of national variations in the incidence of NTDs, with a recent Irish study reporting an increase in the rate. This review compares the periconceptional FA supplementation guidelines between the different countries in Europe. An online search of country-specific guidelines produced before 2015 concerning periconceptional FA supplementation was conducted. If an English version was not available directly, the EUROCAT register was searched for the English version of the recommendations. We identified national guidelines from 20 European countries. Over half recommended that FA supplements be taken by women planning a pregnancy, but three recommended that they should be taken by all women of child-bearing age. Four guidelines recommended starting FA at least 4 weeks preconceptionally, but no country recommended starting FA at least 12 weeks preconceptionally as suggested by recently published studies. There is a need for further consideration of the duration of preconceptional FA supplementation specifically. The latest scientific evidence in this area should inform the development of European guidelines on FA, as there is wide variation in current recommendations. Overall, the wide variation in national guidelines concerning periconceptional FA supplementation may in part explain the differences in national rates of NTDs reported by EUROCAT. National guidelines on FA supplementation should be standardised across European countries. PMID:26350391

  2. Folic Acid Supplementation and Preterm Birth: Results from Observational Studies

    PubMed Central

    Franchi, Massimo

    2014-01-01

    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. PMID:24724083

  3. Association between serum folic acid level and erectile dysfunction.

    PubMed

    Karabakan, M; Erkmen, A E; Guzel, O; Aktas, B K; Bozkurt, A; Akdemir, S

    2016-06-01

    This study measured the serum folic acid (FA) level in patients with erectile dysfunction (ED) and evaluated the possible association between the serum FA level and erectile function. The study divided 120 patients with ED into 3 groups of 40 patients each: those with severe, moderate and mild ED. Forty healthy men served as controls. Fasting serum samples were obtained, and the total testosterone, cholesterol and FA levels were measured using chemiluminescent immunoassays. There were no significant differences in the mean age, mean body mass index or mean serum total testosterone and cholesterol levels among the three ED groups and controls (P > 0.05). The mean serum FA concentrations were 7.2 ± 3.7, 7.1 ± 3.2, 10.2 ± 4.6 and 10.7 ± 4.6 ng ml(-1) in the severe, moderate and mild ED and control groups respectively. The mean serum FA concentration was significantly higher in the control group than in the severe and moderate ED groups (both P < 0.001), but not the mild ED group (P = 0.95). Considering the significant differences in the serum FA levels between the control and ED groups, serum FA deficiency might reflect the severity of ED. PMID:26302884

  4. Photoinactivation of tyrosinase sensitized by folic acid photoproducts.

    PubMed

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

    2015-08-01

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

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

    PubMed Central

    2013-01-01

    Background Strenuous physical activity can alter the status of folic acid, a vitamin directly associated with homocysteine (Hcy); alterations in this nutrient are a risk factor for cardiovascular disease. Handball players are a population at risk for nutrient deficiency because of poor dietary habits. Objective The aims of this study were to evaluate nutritional status for macronutrients and folic acid in members of a high-performance handball team, and determine the effect of a nutritional intervention with folic acid supplementation and education. Design A total of 14 high-performance handball players were monitored by recording training time, training intensity (according to three levels of residual heart rate (RHR): <60%, 60%–80% and >80%), and subjective perceived exertion (RPE) during a 4-month training period. Nutritional, laboratory and physical activity variables were recorded at baseline (Week 0), after 2 months of dietary supplementation with 200 μg 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 < 0.01) between Hcy and folic acid concentrations (r = −0.84) at Week 8, reflecting a significant change in Hcy concentration (P < 0.05) as a result of hyperhomocysteinemia following the accumulation of high training loads. At Week 16 we observed a significant negative correlation (P < 0.01) between Hcy concentration and training time with an RHR <60%, indicating that aerobic exercise avoided abrupt changes in Hcy and may thus reduce the risk of cardiovascular accidents in high-performance athletes. Conclusion Integral monitoring and education are needed for practitioners of handball sports to record their folic acid status, a factor that directly affects Hcy metabolism. Folic acid supplementation may protect athletes against alterations that can lead to cardiovascular events related to exertion during competition. PMID:23432819

  6. Maternal folic acid supplementation to dams on marginal protein level alters brain fatty acid levels of their adult offspring.

    PubMed

    Rao, Shobha; Joshi, Sadhana; Kale, Anvita; Hegde, Mahabaleshwar; Mahadik, Sahebarao

    2006-05-01

    Studies on fetal programming of adult diseases have highlighted the importance of maternal nutrition during pregnancy. Folic acid and long-chain essential polyunsaturated fatty acids (LC-PUFAs) have independent effects on fetal growth. However, folic acid effects may also involve alteration of LC-PUFA metabolism. Because marginal deficiency of LC-PUFAs during critical periods of brain growth and development is associated with risks for adult diseases, it is highly relevant to investigate how maternal supplementation of such nutrients can alter brain fatty acid levels. We examined the impact of folic acid supplementation, conventionally used in maternal intervention, on brain essential fatty acid levels and plasma corticosterone concentrations in adult offspring at 11 months of age. Pregnant female rats from 4 groups (6 in each) were fed with casein diets either with 18 g protein/100 g diet (control diet) or treatment diets that were marginal in protein (MP), such as 12 g protein/100 g diet supplemented with 8 mg folic acid (FAS/MP), 12 g protein/100 g diet without folic acid (FAD/MP), or 12 g protein/100 g diet (MP) with 2 mg folic acid. Pups were weaned to a standard laboratory diet with 18 g protein/100 g diet. All male adult offspring in the FAS/MP group showed lower docosahexaenoic acid (P<.05) as compared with control adult offspring (6.04+/-2.28 vs 10.33+/-0.86 g/100 g fatty acids) and higher n-6/n-3 ratio (P<.05). Docosahexaenoic acid levels in FAS/MP adult offspring were also lower (P<.05) when compared with the MP group. Plasma corticosterone concentrations were higher (P<.05) in male adult offspring from the FAS/MP group compared with control as well as the MP adult offspring. Results suggest that maternal folic acid supplementation at MP intake decreased brain docosahexaenoic acid levels probably involving corticosterone increase. PMID:16631439

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

    PubMed

    Scaglione, Francesco; Panzavolta, Giscardo

    2014-05-01

    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

  8. Evidence that folic acid deficiency is a major determinant of hyperhomocysteinemia in Parkinson's disease.

    PubMed

    dos Santos, Eliseu Felippe; Busanello, Estela Natacha Brandt; Miglioranza, Anelise; Zanatta, Angela; Barchak, Alethea Gatto; Vargas, Carmen Regla; Saute, Jonas; Rosa, Charles; Carrion, Maria Júlia; Camargo, Daiane; Dalbem, André; da Costa, Jaderson Costa; de Sousa Miguel, Sandro René Pinto; de Mello Rieder, Carlos Roberto; Wajner, Moacir

    2009-06-01

    In the present work we measured blood levels of total homocysteine ((t)Hcy), vitamin B(12) and folic acid in patients with Parkinson s disease (PD) and in age-matched controls and searched for possible associations between these levels with smoking, alcohol consumption, L-DOPA treatment and disease duration in PD patients. We initially observed that plasma (t)Hcy levels were increased by around 30 % in patients affected by PD compared to controls. Linear correlation, multiple regression and comparative analyses revealed that the major determinant of the increased plasma concentrations of (t)Hcy in PD patients was folic acid deficiency, whereas in controls (t)Hcy levels were mainly determined by plasma vitamin B(12) concentrations. We also observed that alcohol consumption, gender and L-DOPA treatment did not significantly alter plasma (t)Hcy, folic acid and vitamin B(12) levels in parkinsonians. Furthermore, disease duration was positively associated with (t)Hcy levels and smoking was linked with a deficit of folic acid in PD patients. Considering the potential synergistic deleterious effects of Hcy increase and folate deficiency on the central nervous system, we postulate that folic acid should be supplemented to patients affected by PD in order to normalize blood Hcy and folate levels, therefore potentially avoiding these risk factors for neurologic deterioration in this disorder. PMID:19294496

  9. Optimization of folic acid nano-emulsification and encapsulation by maltodextrin-whey protein double emulsions.

    PubMed

    Assadpour, Elham; Maghsoudlou, Yahya; Jafari, Seid-Mahdi; Ghorbani, Mohammad; Aalami, Mehran

    2016-05-01

    Due to susceptibility of folic acid like many other vitamins to environmental and processing conditions, it is necessary to protect it by highly efficient methods such as micro/nano-encapsulation. Our aim was to prepare and optimize real water in oil nano-emulsions containing folic acid by a low energy (spontaneous) emulsification technique so that the final product could be encapsulated within maltodextrin-whey protein double emulsions. A non ionic surfactant (Span 80) was used for making nano-emulsions at three dispersed phase/surfactant ratios of 0.2, 0.6, and 1.0. Folic acid content was 1.0, 2.0, and 3.0mg/mL of dispersed phase by a volume fraction of 5.0, 8.5, and 12%. The final optimum nano-emulsion formulation with 12% dispersed phase, a water to surfactant ratio of 0.9 and folic acid content of 3mg/mL in dispersed phase was encapsulated within maltodextrin-whey protein double emulsions. It was found that the emulsification time for preparing nano-emulsions was between 4 to 16h based on formulation variables. Droplet size decreased at higher surfactant contents and final nano-emulsions had a droplet size<100nm. Shear viscosity was higher for those formulations containing more surfactant. Our results revealed that spontaneous method could be used successfully for preparing stable W/O nano-emulsions containing folic acid. PMID:26806649

  10. Tailoring folic acid and methotrexate-attributed quantum dots for integrated cancer cell imaging and therapy

    NASA Astrophysics Data System (ADS)

    Fahmi, Mochamad Zakki; Chang, Jia-Yaw

    2016-03-01

    Potential application of folic acid and methotrexate-attributed AgInS2-ZnS quantum dots on both detection and therapeutic of cancer cell were intensively investigated on this study. In the initial step, the bright luminescent of QDs, with % QY up to 55.3, were synthesized with one-pot two-step process resulting narrow particle distribution and successfully transferred to water phase without significant effect on optical properties. The water-soluble AgInS2-ZnS quantum dots (QDs) encapsulated with oleylamine have been successfully prepared by ultrasonication assisting. Several aspect including QDs characterization, pH stability, ionic strength, and bonding properties were investigated to reach desired condition of water-soluble AgInS2-ZnS QDs. Folic acid was further conjugated to QDs for HeLa and MCF7 cancer cell imaging to performs the targeting capability. Moreover, folic acid is efficiently internalized into cell through the receptor-mediated endocytosis even when conjugated with a wide variety of molecules. Confocal imaging characterization further informs folic acid-conjugated AgInS2-ZnS QDs could most specific targeted to the human cervical (HeLa) cells. The therapeutic feature of QDs on HeLa cancer cell was conjugated by attributing methotrexate on the QDs, instead of folic acid, and the design could improve on inhibiting the cancer cell viability as well as its fluorescent intensity.

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

    PubMed Central

    2012-01-01

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

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

    PubMed

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

    2013-09-01

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

  13. Folic Acid Supplementation and Pregnancy: More Than Just Neural Tube Defect Prevention

    PubMed Central

    Greenberg, James A; Bell, Stacey J; Guan, Yong; Yu, Yan-hong

    2011-01-01

    Folate (vitamin B9) is an essential nutrient that is required for DNA replication and as a substrate for a range of enzymatic reactions involved in amino acid synthesis and vitamin metabolism. Demands for folate increase during pregnancy because it is also required for growth and development of the fetus. Folate deficiency has been associated with abnormalities in both mothers (anemia, peripheral neuropathy) and fetuses (congenital abnormalities). This article reviews the metabolism of folic acid, the appropriate use of folic acid supplementation in pregnancy, and the potential benefits of folic acid, as well as the possible supplementation of l-methylfolate for the prevention of pregnancy-related complications other than neural tube defects. PMID:22102928

  14. Neuroprotective effects of folic acid on experimental diabetic peripheral neuropathy.

    PubMed

    Yilmaz, Mustafa; Aktug, Huseyin; Oltulu, Fatih; Erbas, Oytun

    2016-05-01

    Diabetic peripheral neuropathy (DPN) is widely considered as a degenerative complication of diabetic patients. The clinical effectiveness of folic acid (FA) on DPN is uncertain. The objective of the present study was to determine the effect of FA in DPN using electromyography (EMG), histopathological examination, immunohistochemistry, inclined plane test, and malondialdehyde (MDA) levels as a marker for lipid peroxidation in experimental diabetic rats. A total of 21 Sprague Dawley rats were randomly divided into 3 groups: control group, diabetes group, and FA-treated group. In EMG, compound muscle action potential (CMAP) amplitude in the sciatic nerve was lower in the diabetes group compared with the control group. CMAP amplitude in the sciatic nerve was higher in the FA-treated group when compared with the diabetes group. Distal latency and CMAP duration in the sciatic nerve were lower in the FA-treated group when compared with the diabetes group. In histopathological examination of the sciatic nerve, peripheral fibrosis was present in the diabetic group; the fibrosis was lower in the FA-treated group. In comparison with the diabetes group, the expression of nerve growth factor (NGF) was higher in the FA-treated group. The scores for the inclined plane test were lower in the diabetes group and higher in the FA-treated group than the control group. The MDA levels were significantly lower in the FA-treated group when compared with the diabetes group.The study suggests that FA can protect diabetic rats against DPN and that the underlying mechanism for this may be related to improvement of the expression of NGF and lower MDA levels. PMID:24311627

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

    PubMed

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

    1991-01-01

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

  16. The dynamics of folic acid metabolism in an adult given a small tracer dose of 14C-folic acid.

    PubMed

    Clifford, A J; Arjomand, A; Dueker, S R; Schneider, P D; Buchholz, B A; Vogel, J S

    1998-01-01

    Folate is an essential nutrient that is involved in many metabolic pathways, including amino acid interconversions and nucleotide (DNA) synthesis. In genetically susceptible individuals and populations, dysfunction of folate metabolism is associated with severe illness. Despite the importance of folate, major gaps exist in our quantitative understanding of folate metabolism in humans. The gaps exist because folate metabolism is complex, a suitable animal model that mimics human folate metabolism has not been identified, and suitable experimental protocols for in vivo studies in humans are not developed. In general, previous studies of folate metabolism have used large doses of high specific activity tritium and 14C-labeled folates in clinical patients. While stable isotopes such as deuterium and 13C-labeled folate are viewed as ethical alternatives to radiolabeled folates for studying metabolism, the lack of sensitive mass spectrometry methods to quantify them has impeded advancement of the field using this approach. In this chapter, we describe a new approach that uses a major analytical breakthrough, Accelerator Mass Spectrometry (AMS). Because AMS can detect attomole concentrations of 14C, small radioactive dosages (nCi) can be safely administered to humans and traced over long periods of time. The needed dosages are sufficiently small that the total radiation exposure is only a fraction of the natural annual background radiation of Americans, and the generated laboratory waste may legally be classified non-radioactive in many cases. The availability of AMS has permitted the longest (202 d) and most detailed study to date of folate metabolism in a healthy adult human volunteer. Here we demonstrate the feasibility of our approach and illustrate its potential by determining empirical kinetic values of folate metabolism. Our data indicate that the mean sojourn time for folate is in the range of 93 to 120 d. It took > or = 350 d for the absorbed portion of small bolus dose of 14C-folic acid to be eliminated completely from the body. PMID:9781393

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

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

  18. Fortification of Corn Masa Flour With Folic Acid in the United States

    PubMed Central

    Oinuma, Motoko

    2011-01-01

    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

  19. Folic acid and human reproduction—ten important issues for clinicians

    PubMed Central

    Dunlap, Beth; Shelke, Kantha; Salem, Shala A.; Keith, Louis G.

    2011-01-01

    This article presents data on the current best evidence-based clinical practices and controversies surrounding folic acid supplementation/fortification for the prevention of neural tube defects (NTDs) during early pregnancy. Formatted as a series of ten clinical questions, answers and extensive discussion are provided for each point. We assess the history and evidence behind supplementation and fortification, racial/ethnic disparities in NTDs on a global scale, and present information on risk factors for NTDs other than dietary folic acid deficiency. Also discussed are public health challenges, including disparities in NTD rates, population-wide monitoring of NTDs, and tracking safety data in the post-fortification era. Emerging data are also reviewed regarding the role folic acid may play in malignant processes, cardiovascular disease, male fertility, and other medical conditions. PMID:21991291

  20. Protective effect of ligand-binding proteins against folic acid loss due to photodecomposition.

    PubMed

    Liang, Li; Zhang, Jie; Zhou, Peng; Subirade, Muriel

    2013-11-15

    The B group vitamin known as folates is essential for a variety of physiological processes and plays an important role in the prevention of neural tube defects. However, it decomposes when exposed to UV light. In this study, the response of the synthetic form of folates known as folic acid to UV irradiation in the presence of β-lactoglobulin (β-LG), bovine serum albumin (BSA) and α-lactalbumin (α-LA) was investigated using circular dichroism, absorbance and fluorescence spectroscopy. Photodecomposition of folic acid was delayed in the presence of the proteins, which ranked in the order β-LG>BSA>α-LA in terms of effectiveness. Protein unfolding or decomposition occurred at the same time, due to interaction with folic acid photodecomposition products. The results suggest potential uses of ligand-binding proteins as carriers of water-soluble active compounds for nutraceutical applications. PMID:23790844

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  3. Assessment of student pharmacists' knowledge concerning folic acid and prevention of birth defects demonstrates a need for further education.

    PubMed

    Lynch, Sean M

    2002-03-01

    Adequate periconceptional consumption of folic acid can prevent neural tube birth defects, and all women capable of becoming pregnant are recommended to consume 400 microg/d. Most women, however, are unaware of this recommendation and do not consume adequate amounts of folic acid. It is important, therefore, that healthcare professionals, such as pharmacists, be capable of educating women regarding folic acid. The aim of this study was to assess knowledge regarding prevention of birth defects by folic acid among student (future) pharmacists in the final year of a professional degree program. Over a 3-y period (1998-2000), students (n = 98) enrolled in a PharmD program completed a survey consisting of five multiple-choice questions concerning folic acid and birth defects. Almost all students (93.9%) correctly identified folic acid as preventing birth defects. Of these students, many also knew that supplementation should begin before pregnancy (73.9%). Fewer, however, were able to correctly identify either the recommended level of intake (55.4%) or good sources of folic acid (57.6-65.2%). These results show that although student (future) pharmacists are aware of folic acid's ability to prevent birth defects, many lack the specific knowledge needed to effectively counsel women in future clinical practice. PMID:11880568

  4. Folic acid protects against arsenic-mediated embryo toxicity by up-regulating the expression of Dvr1

    PubMed Central

    Ma, Yan; Zhang, Chen; Gao, Xiao-Bo; Luo, Hai-Yan; Chen, Yang; Li, Hui-hua; Ma, Xu; Lu, Cai-Ling

    2015-01-01

    As a nutritional factor, folic acid can prevent cardiac and neural defects during embryo development. Our previous study showed that arsenic impairs embryo development by down-regulating Dvr1/GDF1 expression in zebrafish. Here, we investigated whether folic acid could protect against arsenic-mediated embryo toxicity. We found that folic acid supplementation increases hatching and survival rates, decreases malformation rate and ameliorates abnormal cardiac and neural development of zebrafish embryos exposed to arsenite. Both real-time PCR analysis and whole in-mount hybridization showed that folic acid significantly rescued the decrease in Dvr1 expression caused by arsenite. Subsequently, our data demonstrated that arsenite significantly decreased cell viability and GDF1 mRNA and protein levels in HEK293ET cells, while folic acid reversed these effects. Folic acid attenuated the increase in subcellular reactive oxygen species (ROS) levels and oxidative adaptor p66Shc protein expression in parallel with the changes in GDF1 expression and cell viability. P66Shc knockdown significantly inhibited the production of ROS and the down-regulation of GDF1 induced by arsenite. Our data demonstrated that folic acid supplementation protected against arsenic-mediated embryo toxicity by up-regulating the expression of Dvr1/GDF1, and folic acid enhanced the expression of GDF1 by decreasing p66Shc expression and subcellular ROS levels. PMID:26537450

  5. Serum homocysteine, B12 and folic acid concentration in Thai overweight and obese subjects.

    PubMed

    Tungtrongchitr, Rungsunn; Pongpaew, Praneet; Tongboonchoo, Chuthaporn; Vudhivai, Niyomsri; Changbumrung, Supranee; Tungtrongchitr, Anchalee; Phonrat, Benjaluck; Viroonudomphol, Duangkamol; Pooudong, Somchai; Schelp, Frank Peter

    2003-02-01

    This study investigated levels of serum homocysteine, vitamin B12, folic acid, vitamin B6 and vitamin C, in 37 male and 112 female overweight and obese Thai volunteers (body mass index; BMI > or = 25.00), and 23 male and 90 female normal-weight Thai volunteers, who came for a physical check-up at the Out-patient Department, General Practice Section, Rajvithi Hospital, Bangkok from March to October of 2000. Data included anthropometric measurements and waist/hip ratios. All anthropometric variables, except height, were significantly higher for the overweight subjects than for the normal subjects. Statistically significantly higher levels of serum homocysteine were found in the overweight subjects. Serum homocysteine concentrations in overweight and obese males were significantly higher than in overweight and obese females. Serum folic acid and vitamin C in the overweight and obese were found to be statistically significantly lower than in the control subjects. No statistically significant difference in vitamin B12 was found in the overweight and obese subjects compared with the normal control subjects. The medians of serum folic acid and vitamin C concentrations for the overweight and obese males were significantly lower than those of the overweight and obese females. A negative correlation was found between serum folic acid and homocysteine concentrations in all overweight and obese subjects. A significant negative correlation between serum folic acid and vitamin B6 was observed in both male and female overweight and obese subjects. The results of the investigation suggest that homocysteine levels in overweight and obese subjects seem to be caused by insufficient dietary folic acid intake and probably not by B12 deficiency. PMID:12690905

  6. Prevention of neural tube defects with folic acid: The Chinese experience

    PubMed Central

    Ren, Ai-Guo

    2015-01-01

    Neural tube defects (NTDs) are a group of congenital malformations of the central nervous system that are caused by the closure failure of the embryonic neural tube by the 28th day of conception. Anencephaly and spina bifida are the two major subtypes. Fetuses with anencephaly are often stillborn or electively aborted due to prenatal diagnosis, or they die shortly after birth. Most infants with spina bifida are live-born and, with proper surgical treatment, can survive into adulthood. However, these children often have life-long physical disabilities. China has one of the highest prevalence of NTDs in the world. Inadequate dietary folate intake is believed to be the main cause of the cluster. Unlike many other countries that use staple fortification with folic acid as the public health strategy to prevent NTDs, the Chinese government provides all women who have a rural household registration and who plan to become pregnant with folic acid supplements, free of charge, through a nation-wide program started in 2009. Two to three years after the initiation of the program, the folic acid supplementation rate increased to 85% in the areas of the highest NTD prevalence. The mean plasma folate level of women during early and mid-pregnancy doubled the level before the program was introduced. However, most women began taking folic acid supplements when they knew that they were pregnant. This is too late for the protection of the embryonic neural tube. In a post-program survey of the women who reported folic acid supplementation, less than a quarter of the women began taking supplements prior to pregnancy, indicating that the remaining three quarters of the fetuses remained unprotected during the time of neural tube formation. Therefore, staple food fortification with folic acid should be considered as a priority in the prevention of NTDs. PMID:26261765

  7. Folic acid supplementation and dietary folate intake, and risk of preeclampsia

    PubMed Central

    Qiu, J; He, X; Zhou, M; Cui, H; Lv, L; Lin, X; Zhang, C; Zhang, H; Xu, R; Zhu, D; Dang, Y; Han, X; Zhang, H; Bai, H; Chen, Y; Tang, Z; Lin, R; Yao, T; Su, J; Xu, X; Liu, X; Wang, W; Ma, B; Liu, S; Qiu, W; Huang, H; Liang, J; Wang, S; Ehrenkranz, RA; Kim, C

    2015-01-01

    BACKGROUND/OBJECTIVES Folic acid supplementation has been suggested to reduce the risk of preeclampsia. However, results from few epidemiologic studies have been inconclusive. We investigated the hypothesis that folic acid supplementation and dietary folate intake before conception and during pregnancy reduce the risk of preeclampsia. SUBJECTS/METHODS A birth cohort study was conducted in 2010–2012 at the Gansu Provincial Maternity & Child Care Hospital in Lanzhou, China. A total of 10 041 pregnant women without chronic hypertension or gestational hypertension were enrolled. RESULTS Compared with nonusers, folic acid supplement users had a reduced risk of preeclampsia (OR = 0.61, 95% CI: 0.43–0.87). A significant dose–response of duration of use was observed among women who used folic acid supplemention during pregnancy only (P-trend = 0.007). The reduced risk associated with folic acid supplement was similar for mild or severe preeclampsia and for early- or late-onset preeclampsia, although the statistical significant associations were only observed for mild (OR = 0.50, 95% CI: 0.30–0.81) and late-onset (OR = 0.60, 95% CI: 0.42–0.86) preeclampsia. The reduced risk associated with dietary folate intake during pregnancy was only seen for severe preeclampsia (OR = 0.52, 95% CI: 0.31–0.87, for the highest quartile of dietary folate intake compared with the lowest). CONCLUSIONS Our study results suggest that folic acid supplementation and higher dietary folate intake during pregnancy reduce the risk of preeclampsia. Future studies are needed to confirm the associations. PMID:25626412

  8. Memory and Motor Coordination Improvement by Folic Acid Supplementation in Healthy Adult Male Rats

    PubMed Central

    Shooshtari, Maryam Khombi; Moazedi, Ahmad Ali; Parham, Gholam Ali

    2012-01-01

    Objective(s) Previous studies have shown that vitamin B as well as folate supplementation has been implicated in cognitive and neurodegenerative disorders including Alzheimer’s and Parkinson's diseases. The aim of present study was to evaluate the effects of folic acid on passive avoidance task and motor coordination in healthy adult male rats. Materials and Methods Animals were randomly divided into five groups with 10 in each. 1) Sham treated (Veh); received same volume of normal saline as folate vehicle, 2-5) Test groups; each received a single dose of folate (5, 10 and 15 mg/ml/kg, IP daily for one week). At the end of the treatment with folic acid or vehicle, motor coordination in rotarod (after 24 hr) and passive avoidance memory in shuttle box (after 2 and 30 days) were evaluated, respectively. Results The results showed that folic acid (5, 10, and 15 mg/kg) increased short-term (P<0.05, P<0.001) memory while, long term memory affected significantly with doses 10 and 15 mg/kg (P<0.01, P<0.001). On the other hand, folic acid (5 and 10 mg/kg) had significant improving effect on motor coordination (P<0.001, P<0.01) but with 15 mg/kg dose didn't have any effect on motor coordination. Conclusion Our results suggest that folic acid may improve both short- and long-term memories, dose dependently, although it affects motor balance at lower dose. The mechanism of folic acid effects on cognition and motor coordination is unknown and needs more investigations. PMID:23653847

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

    PubMed Central

    2010-01-01

    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. PMID:20824979

  10. Prevention of neural tube defects with folic acid: The Chinese experience.

    PubMed

    Ren, Ai-Guo

    2015-08-01

    Neural tube defects (NTDs) are a group of congenital malformations of the central nervous system that are caused by the closure failure of the embryonic neural tube by the 28(th) day of conception. Anencephaly and spina bifida are the two major subtypes. Fetuses with anencephaly are often stillborn or electively aborted due to prenatal diagnosis, or they die shortly after birth. Most infants with spina bifida are live-born and, with proper surgical treatment, can survive into adulthood. However, these children often have life-long physical disabilities. China has one of the highest prevalence of NTDs in the world. Inadequate dietary folate intake is believed to be the main cause of the cluster. Unlike many other countries that use staple fortification with folic acid as the public health strategy to prevent NTDs, the Chinese government provides all women who have a rural household registration and who plan to become pregnant with folic acid supplements, free of charge, through a nation-wide program started in 2009. Two to three years after the initiation of the program, the folic acid supplementation rate increased to 85% in the areas of the highest NTD prevalence. The mean plasma folate level of women during early and mid-pregnancy doubled the level before the program was introduced. However, most women began taking folic acid supplements when they knew that they were pregnant. This is too late for the protection of the embryonic neural tube. In a post-program survey of the women who reported folic acid supplementation, less than a quarter of the women began taking supplements prior to pregnancy, indicating that the remaining three quarters of the fetuses remained unprotected during the time of neural tube formation. Therefore, staple food fortification with folic acid should be considered as a priority in the prevention of NTDs. PMID:26261765

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

    PubMed

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

    2004-01-01

    Neural tube defects (NTDs) are severe congenital malformations and can be fatal. Intake of 0.4 mg folic in the periconceptional period reduces the risk of NTD by 50-70%. Consanguinity in the Arab population in Israel is a prevalent custom. The aim of this study was to assess the level of awareness regarding folic acid and its effect in the prevention of NTD among Arab Israeli women of childbearing age. We conducted a cross-sectional study. Of the 653 women (18-45 years) who were randomly selected for interview while visiting their family physician or well-baby clinic, 624 women completed the questionnaire. Fifty-three percent (n = 333) of the respondents had heard of folic acid; 14% (n = 89) were familiar with the protective effect of NTD and 3% (n = 18) had taken folic acid in the first months of pregnancy whereas none of them had used it in the preconception period. Highly educated women, women with one or two children, paramedics, and women of high socioeconomic status were more knowledgeable about the protective effects of folic acid (P < 0.001). Age and religion had no significant effect. An urgent need exists to improve the awareness of this population to the protective effect of folic acid. Daily supplementation and fertification of food with folic acid should be considered as the best way to improve the balance of folic acid in women of childbearing age of this special population (high prevalence of consanguinity). PMID:15050876

  12. Folic acid supplementation for the prevention of neural tube defects. Should it be a priority for developing countries?

    PubMed

    Perez-escamilla, R

    1997-12-01

    Folic acid supplementation during pregnancy has been widely advocated for the prevention of neural tube defects in developing countries. The author of this letter, however, argues that such a strategy is unwarranted and a misuse of scarce resources. Folic acid deficiency is not the primary cause of neural tube defects and the incidence of this defect is similar in developed and developing countries. It has been estimated that folic acid fortification of cereal-based products--an exceedingly difficult, expensive intervention--would prevent only about 1000 neural tube defect cases per year. Moreover, additional folic acid can prevent neural tube defects only if consumed during the periconceptional period. Although women at risk of neural tube defect recurrence are advised to take 4 mg of folic acid per day when they plan to become pregnant, the recommendation for the vast majority of women in developing countries is increased consumption of beans, oranges, and green leafy vegetables. PMID:12293181

  13. Folic Acid Inhibits Amyloid β-Peptide Production through Modulating DNA Methyltransferase Activity in N2a-APP Cells

    PubMed Central

    Li, Wen; Jiang, Mingyue; Zhao, Shijing; Liu, Huan; Zhang, Xumei; Wilson, John X.; Huang, Guowei

    2015-01-01

    Alzheimer’s disease (AD) is a common neurodegenerative disease resulting in progressive dementia, and is a principal cause of dementia among older adults. Folate acts through one-carbon metabolism to support the methylation of multiple substrates. We hypothesized that folic acid supplementation modulates DNA methyltransferase (DNMT) activity and may alter amyloid β-peptide (Aβ) production in AD. Mouse Neuro-2a cells expressing human APP695 were incubated with folic acid (2.8–40 μmol/L), and with or without zebularine (the DNMT inhibitor). DNMT activity, cell viability, Aβ and DNMTs expression were then examined. The results showed that folic acid stimulated DNMT gene and protein expression, and DNMT activity. Furthermore, folic acid decreased Aβ protein production, whereas inhibition of DNMT activity by zebularine increased Aβ production. The results indicate that folic acid induces methylation potential-dependent DNMT enzymes, thereby attenuating Aβ production. PMID:26492244

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Iron and zinc deficiencies have been associated with delayed motor development in nutritionally at-risk children, albeit inconsistently. In this community-based, randomized double-blind trial, iron+folic acid (FeFA) (12.5 mg Fe + 50 'g folic acid), zinc (Zn) (10 mg), and iron+folic acid+zinc (FeFA+Z...

  15. Periconceptional folic acid use and the prevalence of positional plagiocephaly.

    PubMed

    Michels, Alice; El Bakkali, Nadia; Bastiaenen, Caroline H; De Bie, Rob A; Colla, Carlo G; Van der Hulst, Rene R

    2008-01-01

    The incidence of positional plagiocephaly (PP) has increased during the last 2 decades in the Netherlands. Although this is generally solely attributed to the advice to put babies on the back during their sleep, other factors might be of influence. Because the advice to take folic acid (FA) was initiated in the same period as the sleeping advice, this study was undertaken to evaluate the effect of FA on PP. It is known that a daily intake of 400 microg of FA around the time of conception is advised in periconceptive women to prevent development of neural tube defects. The maximal daily dietary folate intake is considered to be 250 mg with a bioavailability of 50% to 70%. However, periconceptional women may take a multivitamin containing pteroylmonoglutamine in addition to a FA supplement (isolated pteroylmonoglutamine). Therefore, the daily intake of FA will exceed 1 mg daily, which is considered the upper limit of daily folate ingestion. Data from the "Maastricht Cohort and Intervention study about pregnancy related girdlepain" were used to study the amount of folate containing supplemental intake of all the 7526 women. In this study, women were prospectively questioned about their FA intake. The entire cohort, considered the control group, was compared with a subgroup of women within this cohort with children with PP, treated by a plastic surgeon, considered the PP group. Double use, defined as isolated FA preparations in addition to folate containing supplements (vitamins), was seen more frequently in women giving birth to children with PP. In the PP group, double use was seen in 33.3% of the women compared to 13.2% in the control group. Although no statistical analysis could be made because the PP group was too small, the use of too high dosages of FA might have an adverse effect in causing more PP. This article does not want to discuss the beneficial effect of FA during pregnancy. However, we observed a potential empirical relation between PP and FA double intake requiring attention in more extensive studies. PMID:18216662

  16. Folic acid in pregnancy and mortality from cancer and cardiovascular disease: further follow-up of the Aberdeen folic acid supplementation trial

    PubMed Central

    Taylor, Caroline M; Atkinson, Charlotte; Penfold, Chris; Bhattacharya, Sohinee; Campbell, Doris; Davey Smith, George; Leary, Sam; Ness, Andy

    2015-01-01

    Background Supplemental periconceptional folic acid is recommended to reduce the risk of fetal neural tube defects. A previous report indicated an elevated risk of breast cancer and all cancer deaths in later life among women randomised by alternate allocation to high-dose (5 mg/day) folic acid in pregnancy compared with placebo; however, findings were based on small numbers of cases. Our aim was to extend the previous analysis by including data from an additional 10 years of follow-up. Methods Records of participants in a large (n=2928) trial of folate supplementation (5 or 0.2 mg folic acid, or placebo) in pregnancy in the 1960s were linked to central registries in Scotland. Unadjusted and adjusted HRs were calculated for all-cause, cardiovascular, all cancer and breast cancer mortality, and all cancer and breast cancer morbidity. Analyses were done using (1) data from the time of the previous linkage (2002) to March 2013; and (2) data from 1980 to March 2013. Results There was no evidence to suggest an excess risk of morbidity or mortality in either supplementation group compared with placebo for 2002–2013 and no associations were seen for the full time period (1980–2013). Conclusions Findings from this extended follow-up do not support our previous observation of an elevated risk of mortality from breast cancer or all cancers in later life among women who had taken 5 mg folic acid/day during pregnancy. Furthermore, there were no associations with risk of mortality from all-causes, all cancers or cardiovascular disease. PMID:25855124

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

    SciTech Connect

    Dawson, Jennifer E.; Raymond, Angela M.; Winn, Louise M. . E-mail: winnl@biology.queensu.ca

    2006-03-01

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

  18. A history of the isolation and identification of folic acid (folate).

    PubMed

    Rosenberg, Irwin H

    2012-01-01

    In the 1930s, Lucy Wills identified a 'new hemopoietic factor' in yeast and liver which cured tropical macrocytic anemia in humans and experimental anemia in monkeys. Janet Watson and William B. Castle named the unknown substance, which would ultimately become a form of folate, 'Wills' factor'. Further studies with this unknown substance showed that it was active against nutritional pancytopenia in monkeys and experimental anemia in chicks, leading to various designations such as vitamin M (monkey) and vitamin B(c) (chick). Other factors with growth-promoting activity for microorganisms such as Lactobacillus casei were given the interim names including folic acid - in recognition of extracts from leafy greens. Competing pharmaceutical research groups headed by Robert Stokstad at Lederle Laboratories and Joseph John Pfiffner at Parke-Davis Research Laboratory independently isolated factors bearing the biological properties of Wills' factor and other unknown related factors including folic acid, Lederle Laboratories from a bacterial culture and Parke-Davis Laboratory from yeast and liver as a conjugate of folate. The new vitamin then was crystallized, chemically identified, and synthesized as pteroylglutamic acid and named folic acid between 1943 and 1945. Further studies of the monoglutamic folic acid and the yeast isolate polyglutamyl folate followed through the 1950s and to the present. PMID:23183294

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

    Saltan, Nagehan; Kutlu, H Mehtap; Hür, Deniz; İşcan, Arzu; Say, Rıdvan

    2011-01-01

    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. PMID:21468352

  1. Periconceptional supplementation with folic acid. Does it prevent neural tube defects?

    PubMed

    Murphy, P A

    1992-01-01

    There has been considerable controversy in recent years concerning the benefit of periconceptional vitamin supplementation in the prevention of neural tube defects. Recent reports of a successful randomized clinical trial have prompted official recommendations for folic acid supplementation in women with a history of an affected pregnancy. Periconceptional supplementation of low-risk women remains controversial. PMID:1538265

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

    PubMed

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

    2005-12-01

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

  3. UNMETABOLIZED FOLIC ACID IN PLASMA IS ASSOCIATED WITH REDUCED NATURAL KILLER CELL CYTOTOXICITY AMONG POSTMENOPAUSAL WOMEN

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Folic acid (FA) supplements and food fortification are used to prevent neural tube defects and to lower plasma homocysteine. Through exposure to food fortification and vitamin supplement use, large populations in the USA and elsewhere have an unprecedented high FA intake. We evaluated dietary and su...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  6. Folic acid and homocysteine affect neural crest and neuroepithelial cell outgrowth and differentiation in vitro.

    PubMed

    Boot, Marit J; Steegers-Theunissen, Régine P M; Poelmann, Robert E; Van Iperen, Liesbeth; Lindemans, Jan; Gittenberger-de Groot, Adriana C

    2003-06-01

    The beneficial effect of additional folic acid in the periconceptional period to prevent neural tube defects, orofacial clefts, and conotruncal heart defects in the offspring has been shown. Folate shortage results in homocysteine accumulation. Elevated levels of homocysteine have been related to neural tube defects. We studied the behavior of neuroepithelial cells and cranial and cardiac neural crest cells in vitro. Neural tube explants were cultured for 24 and 48 hr in medium after addition of folic acid and/or homocysteine. Folic acid addition increased neuroepithelial cell outgrowth and increased neural crest cell differentiation into nerve and smooth muscle cells. Addition of homocysteine increased neural crest cell outgrowth and migration from the neural tube and inhibited neural crest cell differentiation. Our findings suggest that neural tube defects caused by folate deficiency and hyperhomocysteinemia develop due to increased neuroepithelial to neural crest cell transformation. This increased transformation leads to a shortage of neuroepithelial cells in the neural tube. Defects in orofacial and conotruncal development are explained by abnormal differentiation of neural crest cells in the presence of high homocysteine concentrations. Our findings supports a critical role for folic acid and homocysteine in the development of neural tube defects and neural crest related heart malformations. PMID:12761857

  7. 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...

  8. Development and application of nanoparticles synthesized with folic acid-conjugated soy protein

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study, soy protein isolate (SPI) was conjugated with folic acid (FA) to prepare nanoparticles for target-specific drug delivery. Successful conjugation was evidenced by UV spectrophotometry and primary amino group analysis. An increase in count rate by at least 142% was observed in FA-conjug...

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  10. MASS SPECTRAL DETERMINATIONS OF THE FOLIC ACID CONTENT OF FORTIFIED BREADS FROM CHILE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sixty-four samples of fortified bread collected from bakeries from Santiago, Chile were assayed for their folic acid (FA) content using high performance liquid chromatography-mass spectrometry (LC-MS). A 13C-labeled analogue of FA was spiked into each sample as an internal standard and the analyte ...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  12. Pros and cons of increasing folic acid and vitamin B12 intake by fortification

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is no doubt that folic acid fortification can be effective for reducing the incidence of neural tube defects (NTDs). The degree of efficacy depends on both the level of folate depletion and other, yet to be fully characterized, genetic and/or environmental factors. This article summarizes brie...

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

    PubMed Central

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

    2011-01-01

    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 μg/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 μg/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 β-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

  14. Protective effects of folic acid against central nervous system neurotoxicity induced by lead exposure in rat pups.

    PubMed

    Quan, F S; Yu, X F; Gao, Y; Ren, W Z

    2015-01-01

    Recent studies found folic acid is associated with lower blood lead (Pb) levels, and folate deficient children are more susceptible to the negative cognitive effects of Pb. This study evaluated the protective effects of folate supplementation against Pb exposure in rat pups and the mechanisms of protection. A total of 72 rats were used. Thirty were administered Pb only; 30, Pb and folic acid at the same time; and 12, only physiological saline. Protective effects of folic acid were examined at 14, 21, and 28 days after treatment. Lower blood Pb levels were found in all of the samples collected from the rats treated with folic acid. Downregulation of Bc1-2 expression and upregulation of Bax expression were observed in the neurons of folic acid-treated rats. Significantly more hematoxylin and eosin stained neurons were found in the folic acid treatment group. Nuclear enrichment and neuron apoptosis were observed by electron microscopy in the Pb-treated group. In conclusion, this study demonstrated that folic acid supplementation might offer efficient protective effects against Pb poisoning in rat pups, which was associated with less neuron damage and lower blood levels of Pb. PMID:26505396

  15. Effect of processing on folic acid fortified Baladi bread and its possible effect on the prevention of colon cancer.

    PubMed

    Omar, Rasha M; Ismail, Hanaa M; El-Lateef, Bothyna M Abd; Yousef, Mokhtar I; Gomaa, Naglaa F; Sheta, Manal

    2009-07-01

    This paper studied the possible effect of folic acid in fortified Baladi bread on the prevention of colon cancer development in rats. Wheat flour samples (82% extraction rate) and soy bean flour were analyzed to determine their folic acid contents using the High Performance Liquid Chromatography (HPLC). Unfortified and folic acid fortified Baladi breads were prepared. Samples from each step of bread preparation were analyzed for folic acid concentration. Protein, fat, ash, fibers and carbohydrates percentages were also determined. Rats were divided into five groups, four of them were injected subcutaneously with dimethylhydrazine (DMH). After 15 weeks, the rats were sacrificed for pathological examination. Results showed that the folic acid content in wheat flour (82% extraction rate) was found to be highly significantly lower than that in soybean flour. After baking, folic acid content in all breads was found to decrease significantly. The highest protein and fat contents were found in soybean flour fortified Baladi bread. The colons of rats of groups 3 (fed 5% soy flour fortified Baladi bread) and 5 (fed Baladi bread fortified with 5% soy flour+8 mg folic acid/kg wheat flour) were the mostly affected by DMH injection as premalignant changes were observed. PMID:19389458

  16. Folic acid supplements in pregnancy and birth outcome: re-analysis of a large randomised controlled trial and update of Cochrane review.

    PubMed

    Charles, Deborah H M; Ness, Andy R; Campbell, Doris; Smith, George Davey; Whitley, Elise; Hall, Marion H

    2005-03-01

    Periconceptual folic acid prevents neural tube defects. The effect of folic acid taken throughout pregnancy is unclear, however. We re-analysed data from a large randomised controlled trial performed between 1966 and 1967 and combined the results with those from trials included in a Cochrane review. A total of 2928 women were randomised: 1977 were allocated to placebo, 466 to folic acid 200 microg/day and 485 to folic acid 5 mg/day. Folic acid supplementation was not associated with any difference in mean birthweight, placental weight or gestational age. When combined with trials in the Cochrane review folic acid at high doses was associated with reduced risk of low birthweight (pooled relative risk 0.73 [95% CI 0.53, 0.99]). We found no conclusive evidence of benefit for folic acid supplementation in pregnant women given from time of booking onwards. PMID:15787886

  17. The role of folic acid on the hyperhomocysteinemia in the Buerger's disease (Thromboangiitis Obliterans)

    PubMed Central

    Beigi, Ali Akbar; Hoghoughi, Mohammad Ali; Eshaghian, Afrooz; Zade, Akbar Hassan; Masoudpour, Hassan

    2014-01-01

    Background: The mechanism underlying Buerger's disease (BD) is still unknown. Recently, thrombophilic conditions predisposing to a hypercoagulable state have been hypothesized as triggers for BD. The aim of the study is to evaluate the prevalence of the hyperhomocysteinemia and level of the anticardiolipin antibodies, and the role of folic acid on the hyperhomocysteinemia and on the rate of the amputations in the patients with BD. Materials and Methods: In an experimental placebo-controlled double-blinded study, between 2004 and 2010, thirty patients with BD were randomly assigned into two groups (14 patients in a drug group and 16 patients in the placebo group). Drug or placebo was administered, and they were followed in 2 and 6 months for homocysteine, Anticardiolipin antibodies and the risk of amputations. Results: At the beginning of the study homocysteine level was higher than normal in 19 patients (63%). There was a significant decrease in homocysteine level during 6 months in folic acid group (P < 0.001), but there was no change in the placebo group. None of our patients had elevated Anticardiolipin antibodies, and there was no change in the level of Anticardiolipin antibody during study. High level of homocysteine did not associate with more amputations during 6 months of study (P > 0.05). Conclusion: This study shows the hyperhomocysteinemia in BD, and the benefit of folic acid treatment in homocysteine lowering, but folic acid doesnt inhibit the risk of major and minor amputation during 6 months of follow-up. Longer follow-up may reveal the role of folic acid in these patients PMID:25657746

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

    PubMed

    Kirke, P N; Daly, L E; Elwood, J H

    1992-12-01

    A randomised trial was initiated in Ireland in 1981 to determine if periconceptional supplementation with either folic acid alone or a multivitamin preparation alone could reduce the recurrence risk of neural tube defects (NTDs) in women with a previously affected pregnancy from 5.0% to 1.0% or less. The trial was concluded before the initial target number of study subjects was reached and without a clear treatment effect being observed. A total of 354 women were randomised to receive one of three treatments: folic acid, multivitamins without folic acid, and folic acid plus multivitamins. At the end of the trial 257 women had had a first trial pregnancy outcome (261 infants/fetuses) where the presence or absence of NTDs was ascertainable. There was one NTD recurrence in the 89 infants/fetuses of women in the multivitamin group and no recurrence in the 172 infants/fetuses of women in the folic acid groups, a non-significant difference. Otherwise eligible women who were pregnant when first contacted constituted a non-randomised control group; there were three recurrences among the 103 infants in this group. The difference in the recurrence rate between the folic acid groups and the non-randomised controls was statistically significant but we have reservations about the validity of this comparison. Although our findings do not provide clear evidence of a protective effect of folic acid supplementation they are consistent with those of the Medical Research Council (MRC) trial which demonstrated the efficacy of folic acid in preventing recurrence of NTDs and they raise the possibility that folic acid may be protective at a much lower dosage than that used in the MRC trial. PMID:1489222

  19. Formation of 10-Formylfolic Acid, a Potent Inhibitor of Dihydrofolate Reductase, in Rat Liver Slices Incubated with Folic Acid

    PubMed Central

    d'Urso-Scott, M.; Uhoch, J.; Bertino, J. R.

    1974-01-01

    During investigation of folate polyglutamate biosynthesis in rat liver slices utilizing [2-14C]folic acid, a folate compound that behaved like a polyglutamate form in the Sephadex G-15 gel filtration system was found to accumulate. Subsequent chromatographic, spectral, chemical, and enzymic studies have indicated that the compound formed in liver slices incubated with [14C]folic acid with and without methotrexate was 10-formyl folate. This folate is of interest in that it is the most potent natural inhibitor of dihydrofolate reductase known and may be capable of serving a regulatory function within the cell. PMID:4527808

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

    NASA Astrophysics Data System (ADS)

    Nan, Alexandrina; Turcu, Rodica; Liebscher, Jürgen

    2013-11-01

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

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

    SciTech Connect

    Nan, Alexandrina; Turcu, Rodica; Liebscher, Jürgen

    2013-11-13

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

  2. Modeling fortification of corn masa flour with folic acid: the potential impact on exceeding the tolerable upper intake level for folic acid, NHANES 2001–2008

    PubMed Central

    Hamner, Heather C.; Tinker, Sarah C.; Berry, R.J.; Mulinare, Joe

    2013-01-01

    Background The Institute of Medicine set a tolerable upper intake level (UL) for usual daily total folic acid intake (1,000 µg). Less than 3% of US adults currently exceed the UL. Objective The objective of this study was to determine if folic acid fortification of corn masa flour would increase the percentage of the US population who exceed the UL. Design We used dietary intake data from NHANES 2001–2008 to estimate the percentage of adults and children who would exceed the UL if corn masa flour were fortified at 140 µg of folic acid/100 g. Results In 2001–2008, 2.5% of the US adult population (aged≥19 years) exceeded the UL, which could increase to 2.6% if fortification of corn masa flour occurred. With corn masa flour fortification, percentage point increases were small and not statistically significant for US adults exceeding the UL regardless of supplement use, sex, race/ethnicity, or age. Children aged 1–8 years, specifically supplement users, were the most likely to exceed their age-specific UL. With fortification of corn masa flour, there were no statistically significant increases in the percentage of US children who were exceeding their age-specific UL, and the percentage point increases were small. Conclusions Our results suggest that fortification of corn masa flour would not significantly increase the percentage of individuals who would exceed the UL. Supplement use was the main factor related to exceeding the UL with or without fortification of corn masa flour and within all strata of sex, race/ethnicity, and age group. PMID:23316130

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

    SciTech Connect

    Robinson, K.; Pilot, T.F.; Meany, J.E. )

    1990-01-01

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

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

    MedlinePlus

    ... Infant Neural Tube Defects: U.S. Preventive Services Task Force Recommendation Summaries for Patients are a service provided ... of Neural Tube Defects: U.S. Preventive Services Task Force Recommen- dation Statement” and “Folic Acid Supplementation for ...

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

    PubMed Central

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

    2014-01-01

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

  6. Optically active supramolecular complexes of water-soluble achiral polythiophenes and folic acid: spectroscopic studies and sensing applications.

    PubMed

    Yao, Zhiyi; Li, Chun; Shi, Gaoquan

    2008-11-18

    Optically active supramolecular complexes of water-soluble achiral polythiophene (PT) derivatives, PMTPA or PMTEA (Chart 1), and folic acid have been prepared; and the complex formation processes have been studied by absorption, emission, and circular dichroism (CD) spectroscopies. The complexes exhibited unique split-type induced CDs in the pi-pi* transition region of PTs, indicating that the molecular chirality of the glutamic acid moiety in folic acid was expressed in PT backbones. The influences of temperature, solvent composition, and the structures of the inducing molecules on the chirality induction to PTs were also investigated, and a possible mechanism for the formation of chiral superstructures was proposed. Furthermore, it was found that, upon addition of folic acid into aqueous solution of PTs (PMTPA or PMTEA), a dramatic color change from yellow to purple along with the emission quenching of PT derivatives was observed. PMTEA, having one fewer carbon in the hydrophobic side chain relative to PMTPA, showed better selectivity toward folic acid sensing over ATP because of its higher solubility in water and the appropriate hydrophilic/hydrophobic balance in the complex. Therefore, it can be applied as a colorimetric and fluorescent probe for detecting folic acid with high selectivity and sensitivity. Besides naked-eye detection of folic acid, the detection limit can be extended to be 10 (-8) M by using fluorometry and PMTEA as the probing molecule. PMID:18947207

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

    PubMed

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

    2014-12-01

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

  8. Arnold Chiari Malformation with Spina Bifida: A Lost Opportunity of Folic Acid Supplementation

    PubMed Central

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

    2014-01-01

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

  9. Folic Acid-conjugated Graphene Oxide loaded with Photosensitizers for Targeting Photodynamic Therapy.

    PubMed

    Huang, Peng; Xu, Cheng; Lin, Jing; Wang, Can; Wang, Xiansong; Zhang, Chunlei; Zhou, Xuejiao; Guo, Shouwu; Cui, Daxiang

    2011-01-01

    Photodynamic therapy (PDT) has emerged as an alternative and promising noninvasive treatment for cancer as well as non-cancer diseases, which involves the uptake of photosensitizers (PSs) by cancer cells followed by irradiation. The use of nanomaterials as carriers of PSs is a very promising approach to improve the development of PDT in clinical medicine. In this study, a novel folic acid-conjugated graphene oxide (GO) was strategically designed and prepared as targeting drug delivery system to achieve higher specificity. The second generation photosensitizer (PS) Chlorin e6 (Ce6) was effectively loaded into the system via hydrophobic interactions and π-π stacking. The nanocarriers can significantly increase the accumulation of Ce6 in tumor cells and lead to a remarkable photodynamic efficacy on MGC803 cells upon irradiation. These suggested that folic acid-conjugated GO loaded Ce6 had great potential as effective drug delivery system in targeting PDT. PMID:21562631

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

    PubMed

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

    2013-10-01

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

  11. Food Additives Permitted for Direct Addition to Food for Human Consumption; Folic Acid. Final rule.

    PubMed

    2016-04-15

    The Food and Drug Administration (FDA or we) is amending the food additive regulations to provide for the safe use of folic acid in corn masa flour. We are taking this action in response to a food additive petition filed jointly by Gruma Corporation, Spina Bifida Association, March of Dimes Foundation, American Academy of Pediatrics, Royal DSM N.V., and National Council of La Raza. PMID:27101640

  12. Voluntary fortification of breakfast cereals with folic acid: contribution to dietary intake in Australia.

    PubMed

    Japar, Devina; Chandra-Hioe, Maria V; Shrestha, Ashok; Arcot, Jayashree

    2016-05-01

    Ready-to-eat breakfast cereals have been voluntarily fortified with folic acid since 1995, with the purpose of reducing the prevalence of neural tube defects in utero. Using data from the recent Australian Health Survey, this study aimed to estimate folate intake from one serving of breakfast cereals (median amount). Various commercial brands were purchased in 2002 (n = 19) and in 2014 (n = 14); folate was determined by microbiological assay and high-pressure liquid chromatography (HPLC). Total folate (μg/100 g) in 2002 and 2014 selections were 144-633 and 147-564, respectively, and mostly comparable to nutrition labels. Folic acid (2014 selection) using HPLC, ranged from 85 to 411 μg/100 g. Intake of 51 g cereals/serving by individuals ≥2 years could contribute 75-288 μg dietary folate equivalent. It seems that folic acid intake among children (2-3 years) exceeds the recommended dietary intake, when certain brands of breakfast cereals are consumed. Accordingly, the benefits and potential detrimental effects of the voluntary fortification need to be further explored. PMID:26903206

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

    PubMed Central

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

    2015-01-01

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

  14. Folic acid-polydopamine nanofibers show enhanced ordered-stacking via π-π interactions.

    PubMed

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

    2015-06-21

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-07-01

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

  16. Targeted delivery of 5-fluorouracil to cholangiocarcinoma cells using folic acid as a targeting agent.

    PubMed

    Ngernyuang, Nipaporn; Seubwai, Wunchana; Daduang, Sakda; Boonsiri, Patcharee; Limpaiboon, Temduang; Daduang, Jureerut

    2016-03-01

    There are limits to the standard treatment for cholangiocarcinoma (CCA) including drug resistance and side effects. The objective of this study was to develop a new technique for carrying drugs by conjugation with gold nanoparticles and using folic acid as a targeting agent in order to increase drug sensitivity. Gold nanoparticles (AuNPs) were functionalized with 5-fluorouracil (5FU) and folic acid (FA) using polyethylene glycol (PEG) shell as a linker (AuNPs-PEG-5FU-FA). Its cytotoxicity was tested in CCA cell lines (M139 and M213) which express folic acid receptor (FA receptor). The results showed that AuNPs-PEG-5FU-FA increased the cytotoxic effects in the M139 and M213 cells by 4.76% and 7.95%, respectively compared to those treated with free 5FU+FA. It is found that the cytotoxicity of the AuNPs-PEG-5FU-FA correlates with FA receptor expression suggested the use of FA as a targeted therapy. The mechanism of cytotoxicity was mediated via mitochondrial apoptotic pathway as determined by apoptosis array. In conclusion, our findings shed some light on the use of gold nanoparticles for conjugation with potential compounds and FA as targeted therapy which contribute to the improvement of anti-cancer drug efficacy. In vivo study should be warranted for its effectiveness of stability, biosafety and side effect reduction. PMID:26706547

  17. Effects of dietary supplements of folic acid and vitamin B12 on metabolism of dairy cows in early lactation.

    PubMed

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

    2007-07-01

    The present experiment was undertaken to determine 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 multiparous Holstein cows assigned to 6 blocks of 4 cows each according to their previous milk production. Supplementary folic acid at 0 or 2.6 g/d and vitamin B12 at 0 or 0.5 g/d were used in a 2 x 2 factorial arrangement. Supplementary folic acid increased milk production from 38.0 +/- 0.9 to 41.4 +/- 1.0 kg/d and milk crude protein yield from 1.17 +/- 0.02 to 1.25 +/- 0.03 kg/d. It also increased plasma Gly, Ser, Thr, and total sulfur AA, decreased Asp, and tended to increase plasma Met. Supplementary B12 decreased milk urea N, plasma Ile, and Leu and tended to decrease Val but increased homocysteine, Cys, and total sulfur AA. Liver concentration of phospholipids was higher in cows fed supplementary B12. Plasma and liver concentrations of folates and B12 were increased by their respective supplements, but the increase in plasma folates and plasma and liver B12 was smaller for cows fed the 2 vitamins together. In cows fed folic acid supplements, supplementary B12 increased plasma glucose and alanine, tended to decrease plasma biotin, and decreased Km of the methylmalonyl-coenzyme A mutase in hepatic tissues following addition of deoxyadenosylcobalamin, whereas it had no effect when cows were not fed folic acid supplements. There was no treatment effect on plasma nonesterified fatty acids as well as specific activity and gene expression of Met synthase and methylmalonyl-coenzyme A mutase in the liver. Ingestion of folic acid supplements by cows fed no supplementary B12 increased total lipid and triacylglycerols in liver, whereas these supplements had no effect in cows supplemented with B12. The increases in milk and milk protein yields due to folic acid supplements did not seem to be dependent on the vitamin B12 supply. However, when vitamin B12 was given in combination with folic acid, utilization of the 2 vitamins seems to be increased, probably more so in extrahepatic tissues. Metabolic efficiency seems also to be improved as suggested by similar lactational performance and dry matter intake for cows fed supplementary folic acid but increased plasma glucose and decreased hepatic lipids in cows fed folic acid and vitamin B12 together. PMID:17582128

  18. [Prevention of neural tube defects: prevalence of folic acid supplementation during pregnancy and associated factors in Pelotas, Rio Grande do Sul State, Brazil].

    PubMed

    Mezzomo, Cíntia Leal Sclowitz; Garcias, Gilberto de Lima; Sclowitz, Marcelo Leal; Sclowitz, Iandora Timm; Brum, Clarice Brinck; Fontana, Tiago; Unfried, Ricardo Issler

    2007-11-01

    To determine folic acid use and associated factors, a cross-sectional population-based study was conducted in all five maternity hospitals in Pelotas, Rio Grande do Sul State, Brazil. Data were collected from April 1 to August 15, 2006 (n = 1,450 women). A standard questionnaire was applied in the hospitals. Statistical analysis used Poisson regression. Prevalence of folic acid consumption during pregnancy was 31.8%, and periconceptional use was 4.3%. The following were associated with folic acid use: white skin color, schooling > 9 years, family income > R$600, age > 30 years, planned pregnancy, > or =7 prenatal visits, knowledge on folic acid, and prenatal care in the private health system. In order to prevent neural tube defects, it is important to promote folic acid use among childbearing-age women and to supply folic acid to poor women. PMID:17952264

  19. Folic acid supplementation improves microvascular function in older adults through nitric oxide-dependent mechanisms.

    PubMed

    Stanhewicz, Anna E; Alexander, Lacy M; Kenney, W Larry

    2015-07-01

    Older adults have reduced vascular endothelial function, evidenced by attenuated nitric oxide (NO)-dependent cutaneous vasodilatation. Folic acid and its metabolite, 5-methyltetrahydrofolate (5-MTHF), are reported to improve vessel function. We hypothesized that (i) local 5-MTHF administration and (ii) chronic folic acid supplementation would improve cutaneous microvascular function in ageing through NO-dependent mechanisms. There were two separate studies in which there were 11 young (Y: 22 ± 1 years) and 11 older (O: 71 ± 3 years) participants. In both studies, two intradermal microdialysis fibres were placed in the forearm skin for local delivery of lactated Ringer's solution with or without 5 mM 5-MTHF. Red cell flux was measured by laser-Doppler flowmetry. Cutaneous vascular conductance [CVC=red cell flux/mean arterial pressure] was normalized as percentage maximum CVC (%CVCmax) (28 mM sodium nitroprusside, local temperature 43°C). In study 1 after CVC plateaued during local heating, 20 mM NG-nitro-L-arginine methyl ester (L-NAME) was perfused at each site to quantify NO-dependent vasodilatation. The local heating plateau (%CVCmax: O = 82 ± 3 vs Y = 96 ± 1, P = 0.002) and NO-dependent vasodilatation (%CVCmax: O = 26 ± 6% vs Y = 49 ± 5, P = 0.03) were attenuated in older participants. 5-MTHF augmented the overall (%CVCmax = 91 ± 2, P = 0.03) and NO-dependent (%CVCmax = 43 ± 9%, P = 0.04) vasodilatation in older but not young participants. In study 2 the participants ingested folic acid (5 mg/day) or placebo for 6 weeks in a randomized, double-blind, crossover design. A rise in oral temperature of 1°C was induced using a water-perfused suit, body temperature was held and 20 mM L-NAME was perfused at each site. Older participants had attenuated reflex (%CVCmax: O = 31 ± 8 vs Y = 44 ± 5, P = 0.001) and NO-dependent (%CVCmax: O = 9 ± 2 vs Y = 21 ± 2, P = 0.003) vasodilatation. Folic acid increased CVC (%CVCmax = 47 ± 5%, P = 0.001) and NO-dependent vasodilatation (20 ± 3%, P = 0.003) in the older but not the young participants. Both local perfusion of 5-MTHF and supplementation with folic acid increase vasodilatation in ageing individuals through NO-dependent mechanisms. PMID:25748442

  20. Folic acid supplementation during high-fat diet feeding restores AMPK activation via an AMP-LKB1-dependent mechanism.

    PubMed

    Sid, Victoria; Wu, Nan; Sarna, Lindsei K; Siow, Yaw L; House, James D; O, Karmin

    2015-11-15

    AMPK is an endogenous energy sensor that regulates lipid and carbohydrate metabolism. Nonalcoholic fatty liver disease (NAFLD) is regarded as a hepatic manifestation of metabolic syndrome with impaired lipid and glucose metabolism and increased oxidative stress. Our recent study showed that folic acid supplementation attenuated hepatic oxidative stress and lipid accumulation in high-fat diet-fed mice. The aim of the present study was to investigate the effect of folic acid on hepatic AMPK during high-fat diet feeding and the mechanisms involved. Male C57BL/6J mice were fed a control diet (10% kcal fat), a high-fat diet (60% kcal fat), or a high-fat diet supplemented with folic acid (26 mg/kg diet) for 5 wk. Mice fed a high-fat diet exhibited hyperglycemia, hepatic cholesterol accumulation, and reduced hepatic AMPK phosphorylation. Folic acid supplementation restored AMPK phosphorylation (activation) and reduced blood glucose and hepatic cholesterol levels. Activation of AMPK by folic acid was mediated through an elevation of its allosteric activator AMP and activation of its upstream kinase, namely, liver kinase B1 (LKB1) in the liver. Consistent with in vivo findings, 5-methyltetrahydrofolate (bioactive form of folate) restored phosphorylation (activation) of both AMPK and LKB1 in palmitic acid-treated HepG2 cells. Activation of AMPK by folic acid might be responsible for AMPK-dependent phosphorylation of HMG-CoA reductase, leading to reduced hepatic cholesterol synthesis during high-fat diet feeding. These results suggest that folic acid supplementation may improve cholesterol and glucose metabolism by restoration of AMPK activation in the liver. PMID:26400185

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

    PubMed

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

    2013-08-15

    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

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

    TOXLINE Toxicology Bibliographic Information

    Mallard SR; Gray AR; Houghton LA

    2012-01-01

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

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

    PubMed

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

    2015-01-16

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

  4. Maternal and postweaning folic acid supplementation interact to influence body weight, insulin resistance, and food intake regulatory gene expression in rat offspring in a sex-specific manner.

    PubMed

    Huot, Pedro S P; Ly, Anna; Szeto, Ignatius M Y; Reza-López, Sandra A; Cho, Daniel; Kim, Young-In; Anderson, G Harvey

    2016-04-01

    Maternal intake of multivitamins or folic acid above the basal dietary requirement alters the growth and metabolic trajectory of rat offspring. We hypothesized that a modest increase in the folic acid content of maternal diets would alter the offspring's metabolic phenotype, and that these effects could be corrected by matching the folic acid content of the offspring's diet with that of the maternal diet. Female Sprague-Dawley rats were placed on a control or a 2.5× folic acid-supplemented diet prior to mating and during pregnancy and lactation. At weaning, pups from each maternal diet group were randomized to the control or to the 2.5× folic acid-supplemented diet for 25 weeks. Male pups from dams fed the folic acid-supplemented diet were 3.7% heavier than those from control-fed dams and had lower mRNA expression for leptin receptor Obrb isoform (Lepr) (11%) and Agouti-related protein (Agrp) (14%). In contrast, female pups from folic acid-supplemented dams were 5% lighter than those from control-fed dams and had lower proopiomelanocortin (Pomc) (42%), Lepr (32%), and Agrp (13%), but higher neuropeptide Y (Npy) (18%) mRNA expression. Folic acid supplementation ameliorated the alterations induced by maternal folic acid supplementation in male pups and led to the lowest insulin resistance, but the effects were smaller in female pups and led to the highest insulin resistance. In conclusion, maternal folic acid supplementation at 2.5× the control level was associated with alterations in body weight and hypothalamic gene expression in rat offspring in a sex-specific manner, and some of these effects were attenuated by postweaning folic acid supplementation. PMID:26989972

  5. Bioavailability of iron, vitamin A, zinc, and folic acid when added to condiments and seasonings.

    PubMed

    Degerud, Eirik M; Manger, Mari Skar; Strand, Tor A; Dierkes, Jutta

    2015-11-01

    Seasonings and condiments can be candidate vehicles for micronutrient fortification if consumed consistently and if dietary practices ensure bioavailability of the nutrient. In this review, we identify factors that may affect the bioavailability of iron, vitamin A, zinc, and folic acid when added to seasonings and condiments and evaluate their effects on micronutrient status. We take into consideration the chemical and physical properties of different forms of the micronutrients, the influence of the physical and chemical properties of foods and meals to which fortified seasonings and condiments are typically added, and interactions between micronutrients and the physiological and nutritional status of the target population. Bioavailable fortificants of iron have been developed for use in dry or fluid vehicles. For example, sodium iron ethylenediaminetetraacetic acid (NaFeEDTA) and ferrous sulfate with citric acid are options for iron fortification of fish and soy sauce. Furthermore, NaFeEDTA, microencapsulated ferrous fumarate, and micronized elemental iron are potential fortificants in curry powder and salt. Dry forms of retinyl acetate or palmitate are bioavailable fortificants of vitamin A in dry candidate vehicles, but there are no published studies of these fortificants in fluid vehicles. Studies of zinc and folic acid bioavailability in seasonings and condiments are also lacking. PMID:26469774

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

    NASA Astrophysics Data System (ADS)

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

    2007-09-01

    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.

  7. Effects of folic acid supplementation on serum homocysteine and lipoprotein (a) levels during pregnancy

    PubMed Central

    Hekmati Azar Mehrabani, Zohreh; Ghorbanihaghjo, Amir; Sayyah Melli, Manizheh; Hamzeh-Mivehroud, Maryam; Fathi Maroufi, Nazila; Bargahi, Nasrin; Bannazadeh Amirkhiz, Maryam; Rashtchizadeh, Nadereh

    2015-01-01

    Introduction:There are many ideas concerning the etiology and pathogenesis of preeclampsia including endothelial dysfunction, inflammation and angiogenesis. Elevated levels of total homocysteine (Hcy) and lipoprotein (a) [Lp(a)] are risk factors for endothelial dysfunction. This study aimed to evaluate the effect of high dose folic acid (FA) on serum Hcy and Lp(a) concentrations with respect to methylenetetrahydrofolate reductase (MTHFR) polymorphisms 677C→T during pregnancy. Methods: In a prospective uncontrolled intervention, 90 pregnant women received 5 mg FA supplementation before pregnancy till 36th week of pregnancy. The MTHFR polymorphisms 677C→T, serum lactate dehydrogenase activity, urine protein and creatinine concentrations were measured before starting folic acid administration. Serum levels of Hcy and Lp(a) were determined before and after completion of folic acid supplementation period. Results: Supplementation of the patients with FA for 36 week decreased the median (minimum– maximum) levels of serum Hcy from 11.40 μmol/L (4.40-28.70) to 9.70 (1.60-20.80) μmol/L (p=0.001). There was no significant change in serum Lp(a) after FA supplementation (p=0.17). The overall prevalence of genotypes in pregnant women that were under study for MTHFR C677T polymorphism was 53.3% CC, 26.7% CT and 20.0% TT. There was no correlation between decreasing level of serum Hcy in the patients receiving FA and MTHFR polymorphisms. Conclusion:Although FA supplementation decreased serum levels of Hcy in different MTHFR genotypes, serum Lp(a) was not changed by FA supplements. Our data suggests that FA supplementation effects on serum Hcy is MTHFR genotype independent in pregnant women. PMID:26929921

  8. Folic Acid Intake and Neural Tube Defects: Two Egyptian Centers Experience

    PubMed Central

    El-Shabrawi, Mortada H.; Kamal, Naglaa Mohamed; Elhusseini, Mona Abbas; Hussein, Laila; Abdallah, Enas Abdallah Ali; Ali, Yahia Zakaria Abdelalim; Azab, Ahmed Abelfattah; Salama, Mostafa Abdelazim; Kassab, Muna; Krawinkel, Michael

    2015-01-01

    Abstract Neural tube defects (NTDs) are a group of congenital malformations with worldwide distribution and complex etiopathogenesis. Folic acid plays a pivotal role in their prevention. We aimed to identify the protective effect of folic acid intake against NTDs and its dependence on different socioeconomic and environmental factors in a cohort of mothers in Egypt. A cross-sectional study was carried over a period of 12 months on mothers who gave birth to babies with NTDs (group 1) and a control group with healthy offsprings (group 2). Both groups completed 2 questionnaires: food frequency questionnaire targeting the daily folate intake, and socioeconomic status and medical history questionnaire. Both groups of mothers received folate <800 μg/day, recommended for pregnant women. A strong association was detected between NTDs and urban residency with medium educated mothers, with negative consanguinity, who had folate intake < 400 μg daily, and who had their food long cooked. Each of these factors separately had a limited impact to cause NTDs, but when present together they did augment each other. Interestingly enough is the role of fava bean, cauliflower, spinach, and mango in predisposing of NTDs in the presence of the above-mentioned factors. The protective effect of folic acid intake against NTDs may depend on the synergism of different socioeconomic and environmental factors (which differ from country to another). In Egypt, females especially the medium-educated who live in urban areas should be well-informed with the value of folate intake in the periconceptional period. PMID:26376380

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

    PubMed Central

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

    2014-01-01

    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 χ2 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) μmol/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 μmol/l (P = 0.04) and in the control group, there was an increase of 1.05 μmol/l (P = 0.16). Conclusions: In children on AED treatment, folic acid supplementation may reduce tHcy level and thus reduce CVD risk. PMID:24799812

  10. Folic Acid Intake and Neural Tube Defects: Two Egyptian Centers Experience.

    PubMed

    El-Shabrawi, Mortada H; Kamal, Naglaa Mohamed; Elhusseini, Mona Abbas; Hussein, Laila; Abdallah, Enas Abdallah Ali; Ali, Yahia Zakaria Abdelalim; Azab, Ahmed Abelfattah; Salama, Mostafa Abdelazim; Kassab, Muna; Krawinkel, Michael

    2015-09-01

    Neural tube defects (NTDs) are a group of congenital malformations with worldwide distribution and complex etiopathogenesis. Folic acid plays a pivotal role in their prevention. We aimed to identify the protective effect of folic acid intake against NTDs and its dependence on different socioeconomic and environmental factors in a cohort of mothers in Egypt. A cross-sectional study was carried over a period of 12 months on mothers who gave birth to babies with NTDs (group 1) and a control group with healthy offsprings (group 2). Both groups completed 2 questionnaires: food frequency questionnaire targeting the daily folate intake, and socioeconomic status and medical history questionnaire. Both groups of mothers received folate <800 μg/day, recommended for pregnant women. A strong association was detected between NTDs and urban residency with medium educated mothers, with negative consanguinity, who had folate intake < 400 μg daily, and who had their food long cooked. Each of these factors separately had a limited impact to cause NTDs, but when present together they did augment each other. Interestingly enough is the role of fava bean, cauliflower, spinach, and mango in predisposing of NTDs in the presence of the above-mentioned factors. The protective effect of folic acid intake against NTDs may depend on the synergism of different socioeconomic and environmental factors (which differ from country to another). In Egypt, females especially the medium-educated who live in urban areas should be well-informed with the value of folate intake in the periconceptional period. PMID:26376380

  11. Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women.

    PubMed

    Troen, Aron M; Mitchell, Breeana; Sorensen, Bess; Wener, Mark H; Johnston, Abbey; Wood, Brent; Selhub, Jacob; McTiernan, Anne; Yasui, Yutaka; Oral, Evrim; Potter, John D; Ulrich, Cornelia M

    2006-01-01

    Folic acid (FA) supplements and food fortification are used to prevent neural tube defects and to lower plasma homocysteine. Through exposure to food fortification and vitamin supplement use, large populations in the United States and elsewhere have an unprecedented high FA intake. We evaluated dietary and supplemental intakes of folate and FA in relation to an index of immune function, natural killer cell (NK) cytotoxicity, among 105 healthy, postmenopausal women. Among women with a diet low in folate (<233 microg/d), those who used FA-containing supplements had significantly greater NK cytotoxicity (P = 0.01). However, those who consumed a folate-rich diet and in addition used FA supplements > 400 microg/d had reduced NK cytotoxicity compared with those consuming a low-folate diet and no supplements (P = 0.02). Prompted by this observation, we assessed the presence of unmetabolized FA in plasma as a biochemical marker of excess FA. Unmetabolized folic acid was detected in 78% of plasma samples from fasting participants. We found an inverse relation between the presence of unmetabolized FA in plasma and NK cytotoxicity. NK cytotoxicity was approximately 23% lower among women with detectable folic acid (P = 0.04). This inverse relation was stronger among women >or= 60 y old and more pronounced with increasing unmetabolized FA concentrations (P-trend = 0.002). Because of the increased intake of FA in many countries, our findings highlight the need for further studies on the effect of long-term high FA intake on immune function and health. PMID:16365081

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

    PubMed

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

    2015-06-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  15. Microwave-assisted polyol synthesis of carbon nitride dots from folic acid for cell imaging

    PubMed Central

    Guan, Weiwei; Gu, Wei; Ye, Ling; Guo, Chenyang; Su, Su; Xu, Pinxiang; Xue, Ming

    2014-01-01

    A green, one-step microwave-assisted polyol synthesis was employed to prepare blue luminescent carbon nitride dots (CNDs) using folic acid molecules as both carbon and nitrogen sources. The as-prepared CNDs had an average size of around 4.51 nm and could be well dispersed in water. Under excitation at 360 nm, the CNDs exhibited a strong blue luminescence and the quantum yield was estimated to be 18.9%, which is greater than that of other reported CNDs. Moreover, the CNDs showed low cytotoxicity and could efficiently label C6 glioma cells, demonstrating their potential in cell imaging. PMID:25382977

  16. Characterization of folic acid/native cyclodextrins host-guest complexes in solution

    NASA Astrophysics Data System (ADS)

    Ceborska, Magdalena; Zimnicka, Magdalena; Wszelaka-Rylik, Małgorzata; Troć, Anna

    2016-04-01

    The complexation of folic acid (FA) with native cyclodextrins was studied and this process was used for the comparison of 1H NMR, ITC and ESIMS for the evaluation of association constants. The stability increases in the series: α-cyclodextrin/FA < γ-cyclodextrin/FA < β-cyclodextrin/FA. 1H NMR and ITC gave comparable results in regard to association constant values, while results obtained for MS were considerably higher due to different interactions (electrostatic instead of hydrophobic) responsible for the stabilization of the complexes. The dimerization of FA in water was also studied, as well as its impact on the process of complexation with native cyclodextrins.

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

    PubMed

    Hamner, Heather C; Tinker, Sarah C

    2014-04-01

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

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

    PubMed

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

    2006-01-01

    Periconceptional folic acid supplementation is recommended to prevent congenital malformations, mainly neural tube defects, but only 7% of pregnant women in Saxony-Anhalt (Germany) take folic acid at least 4 weeks before conception and in the first 3 months of pregnancy. From March to June 2004, we sent standardized questionnaires about folic acid and its importance during pregnancy to 33 schools in the Federal State of Saxony-Anhalt. A total of 4332 young people aged 1521 years completed the questionnaire, of which 2632 were girls (61%) and 1685 were boys (39%). The majority of them (61%) had heard about folic acid, but only 5% knew that it is a vitamin and 0.7% were aware of the physiological functions of folic acid. Only 22% of the young people answered that folic acid should be taken before and during pregnancy, whereas almost all respondents knew other precautions during pregnancy, e.g. "no smoking" and "no alcohol". Our survey shows that the level of awareness of the importance of folic acid at schools is very low. We suggest that the problem of folic acid should be included in the curricula of biology classes at schools to spread the knowledge of this subject among young people. PMID:16682762

  19. Knowledge and use of folic acid among college women: a pilot health promotion program led by pharmacy students and faculty

    PubMed Central

    Murphy, Bethany L.; Dipietro, Natalie A.; Kier, Karen L.

    2010-01-01

    As pharmacists and pharmacy students are increasingly called upon to assume roles in public health activities, it is important to recognize unique opportunities to educate community members on health, wellness, and disease prevention. Objective To evaluate the impact of a pilot health promotion program on college women’s knowledge regarding folic acid and prevention of neural tube defects (NTD) and frequency of multivitamin use. Methods A health promotion program was developed by a pharmacy student and two pharmacy faculty members that included an oral presentation and reminder messages. A multiple-choice test assessing knowledge of folic acid and NTD and frequency of multivitamin use was given to participants before and immediately after the presentation. Participants then received a reminder message regarding folic acid once a week for three weeks. Knowledge and multivitamin use were reassessed four weeks post-intervention. Results Thirty-two college women voluntarily attended the oral presentation. Twenty-five women (78.2%) completed the four-week post-test. Compared to the pre-test, there were statistically significant increases in average test score (p<0.0001) and correct responses to questions regarding folic acid and NTD (p<0.05 for each question). Participants reported a statistically significant increase in regular (≥4 times/week) multivitamin use (p=0.023). Conclusion Participants in the pilot health promotion program demonstrated a statistically significant increase in knowledge about folic acid and frequency of multivitamin use. A similarly-modeled health promotion program may be an effective way of increasing folic acid and NTD knowledge and changing behaviors of multivitamin use in college women. PMID:25126144

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

    PubMed

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

    2015-06-01

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

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

    PubMed Central

    Sarmah, Swapnalee; Marrs, James A.

    2014-01-01

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

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

    PubMed Central

    Bártfai, Zoltán; Bánhidy, Ferenc

    2011-01-01

    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’). PMID:25083211

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

    PubMed

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

    2009-12-01

    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

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

    PubMed Central

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

    2011-01-01

    Angelman syndrome (AS) is caused by reduced or absent expression of the maternally inherited ubiquitin protein ligase 3A gene (UBE3A), which maps to chromosome 15q11q13. UBE3A is subject to genomic imprinting in neurons in most regions of the brain. Expression of UBE3A from the maternal chromosome is essential to prevent AS, because the paternally inherited gene is not expressed, probably mediated by antisense UBE3A RNA. We hypothesized that increasing methylation might reduce expression of the antisense UBE3A RNA, thereby increasing UBE3A expression from the paternal gene and ameliorating the clinical phenotype. We conducted a trial using two dietary supplements, betaine and folic acid to promote global levels of methylation and attempt to activate the paternally inherited UBE3A gene. We performed a number of investigations at regular intervals including general clinical and developmental evaluations, biochemical determinations on blood and urine, and electroencephalographic studies. We report herein the data on 48 children with AS who were enrolled in a double-blind placebo-controlled protocol using betaine and folic acid for 1 year. There were no statistically significant changes between treated and untreated children; however, in a small subset of patients we observed some positive trends. PMID:20635355

  5. Immunoassay for folic acid detection in vitamin-fortified milk based on electrochemical magneto sensors.

    PubMed

    Lermo, A; Fabiano, S; Hernández, S; Galve, R; Marco, M-P; Alegret, S; Pividori, M I

    2009-03-15

    An immunoassay-based strategy for folic acid in vitamin-fortified milk with electrochemical detection using magneto sensors is described for the first time. Among direct and indirect competitive formats, best performance was achieved with an indirect competitive immunoassay. The immunological reaction for folic acid (FA) detection was performed, for the first time on the magnetic bead as solid support by the covalent immobilization of a protein conjugate BSA-FA on tosyl-activated magnetic bead. Further competition for the specific antibody between FA in the food sample and FA immobilized on the magnetic bead was achieved, followed by the reaction with a secondary antibody conjugated with HRP (AntiIgG-HRP). Then, the modified magnetic beads were easily captured by a magneto sensor made of graphite-epoxy composite (m-GEC) which was also used as the transducer for the electrochemical detection. The performance of the immunoassay-based strategy with electrochemical detection using magneto sensors was successfully evaluated using spiked-milk samples and compared with a novel magneto-ELISA based on optical detection. The detection limit was found to be of the order of microgl(-1) (13.1 nmoll(-1), 5.8 microgl(-1)) for skimmed milk. Commercial vitamin-fortified milk samples were also evaluated obtaining good accuracy in the results. This novel strategy offers great promise for rapid, simple, cost-effective and on-site analysis of biological and food samples. PMID:19084389

  6. Impact of iron and folic acid supplementation on oxidative stress during pregnancy.

    PubMed

    Lymperaki, E; Tsikopoulos, A; Makedou, K; Paliogianni, E; Kiriazi, L; Charisi, C; Vagdatli, E

    2015-01-01

    The aim of the study was to assess serum total antioxidant capacity (TAC) and the impact of supplements on oxidative stress (OS) during pregnancy. Fifty volunteer pregnant women (21-40 years old), in the 12 ± 2 weeks' and 38 ± 2 weeks' gestation of pregnancy (study group), and 25 non-pregnant healthy women (control group) were enrolled. All pregnant women were divided into two age groups (A1: < 35 years and A2: ≥ 35 years) and four groups according to supplementation (B1: iron, B2: folic acid, B3: both and B4: none). Antioxidant activity was assayed using the TAC kit (Cayman Chemical Co.). Level of statistical significance was p < 0.05. Serum TAC values in all pregnant women in the first trimester were significantly lower, as compared with those of the control group. Levels of TAC increased significantly in the third trimester of pregnancy, especially with folic acid or no supplementation. In conclusion, pregnancy is associated with OS, which is promoted by the administration of iron supplementation. PMID:25692315

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

    PubMed

    Pathak, A; Rajput, S J

    2008-01-01

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

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

    PubMed Central

    Pathak, A.; Rajput, S. J.

    2008-01-01

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

  9. Physiological Characteristics and Production of Folic Acid of Lactobacillus plantarum JA71 Isolated from Jeotgal, a Traditional Korean Fermented Seafood.

    PubMed

    Park, Sun-Young; Do, Jeong-Ryong; Kim, Young-Jin; Kim, Kee-Sung; Lim, Sang-Dong

    2014-01-01

    Folic acid, one of the B group of vitamins, is an essential substance for maintaining the functions of the nervous system, and is also known to decrease the level of homocysteine in plasma. Homocysteine influences the lowering of the cognitive function in humans, and especially in elderly people. In order to determine the strains with a strong capacity to produce folic acid, 190 bacteria were isolated from various kinds of jeotgal and chungkuk-jang. In our test experiment, JA71 was found to contain 9.03μg/mL of folic acid after 24 h of incubation in an MRS broth. This showed that JA71 has the highest folic acid production ability compared to the other lactic acid bacteria that were isolated. JA71 was identified as Lactobacillus plantarum by the result of API carbohydrate fermentation pattern and 16s rDNA sequence. JA71 was investigated for its physiological characteristics. The optimum growth temperature of JA71 was 37℃, and the cultures took 12 h to reach pH 4.4. JA71 proved more sensitive to bacitracin when compared with fifteen different antibiotics, and showed most resistance to neomycin and vancomycin. Moreover, it was comparatively tolerant of bile juice and acid, and displayed resistance to Escherichia coli, Salmonella Typhimurium, and Staphylococcus aureus with restraint rates of 60.4%, 96.7%, and 76.2%, respectively. These results demonstrate that JA71 could be an excellent strain for application to functional products. PMID:26760752

  10. Physiological Characteristics and Production of Folic Acid of Lactobacillus plantarum JA71 Isolated from Jeotgal, a Traditional Korean Fermented Seafood

    PubMed Central

    Lim, Sang-Dong

    2014-01-01

    Folic acid, one of the B group of vitamins, is an essential substance for maintaining the functions of the nervous system, and is also known to decrease the level of homocysteine in plasma. Homocysteine influences the lowering of the cognitive function in humans, and especially in elderly people. In order to determine the strains with a strong capacity to produce folic acid, 190 bacteria were isolated from various kinds of jeotgal and chungkuk-jang. In our test experiment, JA71 was found to contain 9.03μg/mL of folic acid after 24 h of incubation in an MRS broth. This showed that JA71 has the highest folic acid production ability compared to the other lactic acid bacteria that were isolated. JA71 was identified as Lactobacillus plantarum by the result of API carbohydrate fermentation pattern and 16s rDNA sequence. JA71 was investigated for its physiological characteristics. The optimum growth temperature of JA71 was 37℃, and the cultures took 12 h to reach pH 4.4. JA71 proved more sensitive to bacitracin when compared with fifteen different antibiotics, and showed most resistance to neomycin and vancomycin. Moreover, it was comparatively tolerant of bile juice and acid, and displayed resistance to Escherichia coli, Salmonella Typhimurium, and Staphylococcus aureus with restraint rates of 60.4%, 96.7%, and 76.2%, respectively. These results demonstrate that JA71 could be an excellent strain for application to functional products. PMID:26760752

  11. Folic acid

    MedlinePlus

    ... with folate deficiency, including ulcerative colitis, liver disease, alcoholism, and kidney dialysis. Women who are pregnant or ... cancer in people with ulcerative colitis. Liver disease. Alcoholism. Weak bones (osteoporosis). Other conditions. More evidence is ...

  12. Folic Acid

    MedlinePlus Videos and Cool Tools

    ... and pregnancy Zika virus and pregnancy Microcephaly Medicine safety and pregnancy Prescription medicine before and during pregnancy ... your baby Common illnesses New parents Family health & safety Complications & Loss Pregnancy complications Preterm labor & premature birth ...

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

    PubMed Central

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

    1988-01-01

    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

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

    NASA Astrophysics Data System (ADS)

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

    2014-04-01

    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.

  15. Biochemical study on the protective role of folic acid in rabbits treated with chromium (VI).

    PubMed

    El-Demerdash, Fatma M; Yousef, Mokhtar I; Elaswad, Fathia A M

    2006-01-01

    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 group were assigned to one of four treatment groups: 0 mg FA and 0 mg Cr(VI)/kg BW (control); 8.3 microg FA/kg BW; 5 mg Cr(VI)/kg BW; 5 mg Cr(VI) plus 8.3 microg FA/kg BW, respectively. Rabbits were orally administered their respective doses every day for 10 weeks. Results obtained showed that Cr(VI) significantly (P < 0.05) increased the levels of free radicals and the activity of glutathione S-transferase (GST), and decreased the content of sulfhydryl groups (SH groups) in liver, testes, brain, kidney, and lung. The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AlP), acid phosphatase (AcP), and lactate dehydrogenase (LDH) were significantly decreased in liver and testes due to Cr(VI) administration. Also, AlP and AcP activities were significantly decreased in kidney and lung. The activity of acetylcholinesterase (AChE) was significantly decreased in brain and plasma. Contrariwise, the activities of AST and ALT were significantly increased in plasma, while AlP and AcP decreased. Chromium (VI) treatment caused a significant decrease in plasma total protein (TP) and globulin, and increased total lipids (TL), cholesterol, glucose, urea, creatinine, and bilirubin concentrations. Folic acid alone significantly decreased the levels of free radicals in liver, brain, and kidney, and increased the content of SH-group. The activities of AST, ALT, and LDH in liver; AST, ALT, AlP, AcP, and LDH in testes; AcP in kidney; AlP and AcP in lung, and LDH in brain were significantly increased. Plasma TP and albumin were increased, while urea and creatinine were decreased. The presence of FA with Cr(VI) restored the changes in enzyme activities and biochemical parameters. In conclusion, folic acid could be effective in the protection of chromium-induced toxicity. PMID:16785179

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

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

    2012-01-01

    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). PMID:22957928

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  20. Wheat rolls fortified with microencapsulated L-5-methyltetrahydrofolic acid or equimolar folic acid increase blood folate concentrations to a similar extent in healthy men and women.

    PubMed

    Green, Timothy J; Liu, Yazheng; Dadgar, Samira; Li, Wangyang; Böhni, Ruth; Kitts, David D

    2013-06-01

    Mandatory folic acid fortification of grains such as wheat flour has been introduced in several countries to reduce the incidence of neural tube defects. There are concerns, however, that folic acid could mask the hematologic signs of vitamin B-12 deficiency and lead to other adverse health outcomes in the population. Calcium L-5-methyltetrahydrofolic acid (L-5-MTHF), a synthetic form of reduced folate, should not mask vitamin B-12 deficiency and may be safer than folic acid. Unfortunately, L-5-MTHF is not stable in most food matrices such as bread. Microencapsulation of L-5-MTHF with sodium ascorbate and a modified starch is effective at preventing loss of the vitamin during baking and storage. Our aim was to assess the efficacy of wheat rolls fortified with microencapsulated L-5-MTHF or equimolar folic acid compared with wheat rolls containing no added folate (placebo) at increasing blood folate concentrations during 16 wk. Healthy men and women aged 18-45 y (n = 45) were randomly assigned to consume wheat rolls that contained L-5-MTHF (452 μg/d), the molar equivalent of folic acid (400 μg/d), or placebo. At 16 wk, the mean (95% CI) erythrocyte folate was 0.48 (0.27, 0.71) and 0.37 (0.17, 0.57) μmol/L higher in the L-5-MTHF (P < 0.001) and folic acid wheat roll (P = 0.001) groups, respectively, than in the placebo group. Likewise, the mean plasma folate was 23 (12, 34) and 23 (12, 34) nmol/L higher in the L-5-MTHF (P < 0.001) and folic acid wheat roll (P < 0.001) groups, respectively, than in the placebo group. There were no significant differences in blood folate concentrations between the L-5-MTHF and folic acid wheat roll groups. Both microencapsulated L-5-MTHF and folic acid-fortified wheat rolls increased blood folate concentrations compared with placebo. PMID:23616513

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

    NASA Astrophysics Data System (ADS)

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

    2011-12-01

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

  2. Promotion of folate for the prevention of neural tube defects: knowledge and use of periconceptional folic acid supplements in Western Australia, 1992 to 1995.

    PubMed

    Bower, C; Blum, L; O'Daly, K; Higgins, C; Loutsky, F; Kosky, C

    1997-12-01

    To assess changes in knowledge and use of folic acid supplements in relation to a statewide health promotion project for the prevention of neural tube defects, we surveyed general practitioners, pharmacists, women of child-bearing age and pregnant women in Western Australia. We also collected data on wholesale sales of folic acid supplements. By the end of the project, 56.5 per cent of general practitioner respondents knew that the recommended dose of folic acid was 0.5 mg and 70 per cent offered folic acid supplements to women planning pregnancy, 82.5 per cent of responding pharmacists knew the recommended dose, and 87.5 per cent reported an increase in sales of 0.5 mg folic acid. Wholesale sales of 0.5 mg folic acid increased markedly in Western Australia compared with other states. From shopping centre surveys of women of child-bearing age we estimated that their knowledge of the association between folate and spina bifida increased from 8.2 per cent before the project to 67.5 per cent 2.5 years later, and doctors were a major source of information for women. In a 1995 survey of a sample of pregnant women, 43.1 per cent with planned pregnancies had taken folic acid supplements periconceptionally, compared with 19.1 per cent in a similar survey in 1993. PMID:9489188

  3. Improved drug targeting of cancer cells by utilizing actively targetable folic acid-conjugated albumin nanospheres.

    PubMed

    Shen, Zheyu; Li, Yan; Kohama, Kazuhiro; Oneill, Brian; Bi, Jingxiu

    2011-01-01

    Folic acid-conjugated albumin nanospheres (FA-AN) have been developed to provide an actively targetable drug delivery system for improved drug targeting of cancer cells with reduced side effects. The nanospheres were prepared by conjugating folic acid onto the surface of albumin nanospheres using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC) as a catalyst. To test the efficacy of these nanospheres as a potential delivery platform, doxorubicin-loaded albumin nanospheres (DOX-AN) and doxorubicin-loaded FA-AN (FA-DOX-AN) were prepared by entrapping DOX (an anthracycline, antibiotic drug widely used in cancer chemotherapy that works by intercalating DNA) into AN and FA-AN nanoparticles. Cell uptake of the DOX was then measured. The results show that FA-AN was incorporated into HeLa cells (tumor cells) only after 2.0h incubation, whereas HeLa cells failed to incorporate albumin nanospheres without conjugated folic acid after 4.0h incubation. When HeLa cells were treated with the DOX-AN, FA-DOX-AN nanoparticles or free DOX, cell viability decreased with increasing culture time (i.e. cell death increases with time) over a 70h period. Cell viability was always the lowest for free DOX followed by FA-DOX-AN4 and then DOX-AN. In a second set of experiments, HeLa cells washed to remove excess DOX after an initial incubation for 2h were incubated for 70h. The corresponding cell viability was slightly higher when the cells were treated with FA-DOX-AN or free DOX whilst cells treated with DOX-AN nanoparticles remained viable. The above experiments were repeated for non-cancerous, aortic smooth muscle cells (AoSMC). As expected, cell viability of the HeLa cells (with FA receptor alpha, FRα) and AoSMC cells (without FRα) decreased rapidly with time in the presence of free DOX, but treatment with FA-DOX-AN resulted in selective killing of the tumor cells. These results indicated that FA-AN may be used as a promising actively targetable drug delivery system to improve drug targeting to cancer cells. PMID:21035550

  4. High folic acid consumption leads to pseudo-MTHFR deficiency, altered lipid metabolism, and liver injury in mice12345

    PubMed Central

    Christensen, Karen E; Mikael, Leonie G; Leung, Kit-Yi; Lévesque, Nancy; Deng, Liyuan; Wu, Qing; Malysheva, Olga V; Best, Ana; Caudill, Marie A; Greene, Nicholas DE

    2015-01-01

    Background: Increased consumption of folic acid is prevalent, leading to concerns about negative consequences. The effects of folic acid on the liver, the primary organ for folate metabolism, are largely unknown. Methylenetetrahydrofolate reductase (MTHFR) provides methyl donors for S-adenosylmethionine (SAM) synthesis and methylation reactions. Objective: Our goal was to investigate the impact of high folic acid intake on liver disease and methyl metabolism. Design: Folic acid–supplemented diet (FASD, 10-fold higher than recommended) and control diet were fed to male Mthfr+/+ and Mthfr+/− mice for 6 mo to assess gene-nutrient interactions. Liver pathology, folate and choline metabolites, and gene expression in folate and lipid pathways were examined. Results: Liver and spleen weights were higher and hematologic profiles were altered in FASD-fed mice. Liver histology revealed unusually large, degenerating cells in FASD Mthfr+/− mice, consistent with nonalcoholic fatty liver disease. High folic acid inhibited MTHFR activity in vitro, and MTHFR protein was reduced in FASD-fed mice. 5-Methyltetrahydrofolate, SAM, and SAM/S-adenosylhomocysteine ratios were lower in FASD and Mthfr+/− livers. Choline metabolites, including phosphatidylcholine, were reduced due to genotype and/or diet in an attempt to restore methylation capacity through choline/betaine-dependent SAM synthesis. Expression changes in genes of one-carbon and lipid metabolism were particularly significant in FASD Mthfr+/− mice. The latter changes, which included higher nuclear sterol regulatory element-binding protein 1, higher Srepb2 messenger RNA (mRNA), lower farnesoid X receptor (Nr1h4) mRNA, and lower Cyp7a1 mRNA, would lead to greater lipogenesis and reduced cholesterol catabolism into bile. Conclusions: We suggest that high folic acid consumption reduces MTHFR protein and activity levels, creating a pseudo-MTHFR deficiency. This deficiency results in hepatocyte degeneration, suggesting a 2-hit mechanism whereby mutant hepatocytes cannot accommodate the lipid disturbances and altered membrane integrity arising from changes in phospholipid/lipid metabolism. These preliminary findings may have clinical implications for individuals consuming high-dose folic acid supplements, particularly those who are MTHFR deficient. PMID:25733650

  5. Nutri-epigenetics Ameliorates Blood–Brain Barrier Damage and Neurodegeneration in Hyperhomocysteinemia: Role of Folic Acid

    PubMed Central

    Kalani, Anuradha; Kamat, Pradip K.; Givvimani, Srikanth; Brown, Kasey; Metreveli, Naira; Tyagi, Suresh C.

    2014-01-01

    Epigenetic mechanisms underlying nutrition (nutrition epigenetics) are important in understanding human health. Nutritional supplements, for example folic acid, a cofactor in one-carbon metabolism, regulate epigenetic alterations and may play an important role in the maintenance of neuronal integrity. Folic acid also ameliorates hyperhomocysteinemia, which is a consequence of elevated levels of homocysteine. Hyperhomocysteinemia induces oxidative stress that may epigenetically mediate cerebrovascular remodeling and leads to neurodegeneration; however, the mechanisms behind such alterations remain unclear. Therefore, the present study was designed to observe the protective effects of folic acid against hyperhomocysteinemia-induced epigenetic and molecular alterations leading to neurotoxic cascades. To test this hypothesis, we employed 8-weeks-old male wild-type (WT) cystathionine-beta-synthase heterozygote knockout methionine-fed (CBS+/−+Met), WT, and CBS+/−+Met mice supplemented with folic acid (FA) [WT+FA and CBS+/−+ Met+FA, respectively, 0.0057-μg g−1 day−1 dose in drinking water/4 weeks]. Hyperhomocysteinemia in CBS+/−+Met mouse brain was accompanied by a decrease in methylenetet-rahydrofolate reductase and an increase in S-adenosylho-mocysteine hydrolase expression, symptoms of oxidative stress, upregulation of DNA methyltransferases, rise in matrix metalloproteinases, a drop in the tissue inhibitors of metallo-proteinases, decreased expression of tight junction proteins, increased permeability of the blood–brain barrier, neuro-degeneration, and synaptotoxicity. Supplementation of folic acid to CBS+/−+Met mouse brain led to a decrease in the homocysteine level and rescued pathogenic and epigenetic alterations, showing its protective efficacy against homocysteine-induced neurotoxicity. PMID:24122186

  6. Folic acid plus α-tocopherol mitigates amyloid-β-induced neurotoxicity through modulation of mitochondrial complexes activity.

    PubMed

    Figueiredo, Cláudia P; Bicca, Maíra A; Latini, Alexandra; Prediger, Rui Daniel S; Medeiros, Rodrigo; Calixto, João B

    2011-01-01

    Early symptoms of Alzheimer's disease (AD) have been attributed to amyloid-β (Aβ) toxicity. The pathophysiology of AD is complex and involves several different biochemical pathways, including defective Aβ protein metabolism, neuroinflammation, oxidative processes, and mitochondrial dysfunction. In the current study, we assessed the molecular mechanisms, mainly the modifications in the activity of mitochondrial complexes, whereby the association of folic acid and α-tocopherol protects mice against the Aβ-induced neurotoxicity. Oral treatment with folic acid (50 mg/kg) plus α-tocopherol (500 mg/kg), once a day during 14 consecutive days, protected mice against the Aβ₁₋₄₀-induced cognitive decline, synaptic loss, and neuronal death. However, chronic treatment comprising folic acid plus α-tocopherol was ineffective on Aβ-induced glial cell activation, suggesting that the effect of this treatment is independent of anti-inflammatory features. Interestingly, the results obtained in our study suggest that mitochondrial energy metabolism is impaired by the Aβ peptide, and upregulation of mitochondrial genes may be a compensatory response, as demonstrated by the increase in mitochondrial complexes I, II, and IV activity, in the hippocampus of mice, after Aβ₁₋₄₀ injection. Of note, the chronic treatment comprising folic acid plus α-tocopherol prevented the increase in the activity of mitochondrial complexes I and IV induced by Aβ₁₋₄₀. Together, these results show the antioxidant effect of the combination of folic acid and α-tocopherol, as observed by the decrease in NO generation from iNOS and nNOS, preventing an increase in the activity of mitochondrial complexes, mainly I and IV, and the neuronal death induced by the Aβ₁₋₄₀ peptide. PMID:21157027

  7. Effects of folic acid on the development and oxidative stress of mouse embryos exposed to heat stress.

    PubMed

    Koyama, H; Ikeda, S; Sugimoto, M; Kume, S

    2012-12-01

    The development of mammalian pre-implantation embryos is inhibited by heat stress, and the inhibitory effect is associated with excess reactive oxygen species (ROS). Folate is a nutrient with various physiological functions including antioxidative effects. We first investigated the transcript expression for 10 enzymes in the cycle of folate metabolism (folate-methionine cycle) in mouse embryos at the 1-cell, 2-cell, 4- to 8-cell, morula and blastocyst stages using reverse transcription-polymerase chain reaction. All of the transcripts were consistently expressed, except for Mat1a, which was not detected from the 4- to 8-cell stage onward. Next, the effects of folic acid (the synthetic form of folate) on the development and ROS levels of heat-stressed embryos were investigated. One-cell mouse embryos were cultured with or without 1000 ng/ml folic acid basically at 38°C, and in the heat-stressed groups, embryos were exposed to 39.5°C/10 h/day on the first two days of culture. The heat stress significantly (p < 0.05) decreased blastocyst development and cell number and increased ROS levels compared to those in the group not subjected to heat stress; however, among the heat-stressed groups, blastocyst development and cell number were increased and the ROS level was decreased by the addition of folic acid. These results indicate that the mRNA of folate-methionine cycle enzymes are expressed in mouse pre-implantation embryos, suggesting they can independently utilize folate, and the inhibitory effects of heat stress on the development of mouse pre-implantation embryos are ameliorated by folic acid. The ameliorating effects of folic acid may be partly due to its antioxidative property. PMID:22309244

  8. Relative bioavailability of iron and folic acid from a new powdered supplement compared to a traditional tablet in pregnant women

    PubMed Central

    Hartman-Craven, Brenda; Christofides, Anna; O'Connor, Deborah L; Zlotkin, Stanley

    2009-01-01

    Background Deficiencies of iron and folic acid during pregnancy can lead to adverse outcomes for the fetus, thus supplements are recommended. Adherence to current tablet-based supplements is documented to be poor. Recently a powdered form of micronutrients has been developed which may decrease side-effects and thus improve adherence. However, before testing the efficacy of the supplement as an alternate choice for supplementation during pregnancy, the bioavailability of the iron needs to be determined. Our objective was to measure the relative bioavailability of iron and folic acid from a powdered supplement that can be sprinkled on semi-solid foods or beverages versus a traditional tablet supplement in pregnant women. Methods Eighteen healthy pregnant women (24 32 weeks gestation) were randomized to receive the supplements in a crossover design. Following ingestion of each supplement, the changes (over baseline) in serum iron and folate over 8 hours were determined. The powdered supplement contained 30 mg of iron as micronized dispersible ferric pyrophosphate with an emulsifier coating and 600 ?g folic acid; the tablet contained 27 mg iron from ferrous fumarate and 1000 ?g folic acid. Results Overall absorption of iron from the powdered supplement was significantly lower than the tablet (p = 0.003). There was no difference in the overall absorption of folic acid between supplements. Based on the differences in the area under the curve and doses, the relative bioavailability of iron from powdered supplement was lower than from the tablet (0.22). Conclusion The unexpected lower bioavailability of iron from the powdered supplement is contrary to previously published reports. However, since pills and capsules are known to be poorly accepted by some women during pregnancy, it is reasonable to continue to explore alternative micronutrient delivery systems and forms of iron for this purpose. Trial Registration ClinicalTrials.gov NCT00789490 PMID:19635145

  9. Inhibition of Photodegradation of Highly Dispersed Folic Acid Nanoparticles by the Antioxidant Effect of Transglycosylated Rutin.

    PubMed

    Kadota, Kazunori; Semba, Kumi; Shakudo, Ryosuke; Sato, Hideyuki; Deki, Yuto; Shirakawa, Yoshiyuki; Tozuka, Yuichi

    2016-04-20

    We developed highly dispersible and photostable nanoparticles of vitamin, folic acid (FA). FA was wet bead milled with milling and dispersing adjuvants and transglycosylated compounds such as α-glucosyl hesperidin (Hesperidin-G) and rutin (Rutin-G), which solubilized FA. The milled slurries of FA particles with transglycosylated compounds consisted of nanosized particles with a median diameter of <100 nm. The lyophilized formulations of these slurries retained their nanometer size after resuspension in water with no aggregation. The apparent solubility of FA in these formulations was 100-fold higher than that of untreated FA. The solubilizing effect of Rutin-G may affect the particle size reduction and dispersibility of FA. The photostability results showed that the strong antioxidant activity of Rutin-G substantially increased the photostability of FA solution. On the basis of these results, bead milling of FA with Rutin-G is a promising technique for developing highly dispersible, photostable nanoparticle FA formulations. PMID:27039660

  10. Folic acid supplementation influences the distribution of neural tube defect subtypes: A registry-based study.

    PubMed

    Bergman, J E H; Otten, E; Verheij, J B G M; de Walle, H E K

    2016-01-01

    Periconceptional folic acid (FA) reduces neural tube defect (NTD) risk, but seems to have a varying effect per NTD subtype. We aimed to study the effect of FA supplementation on NTD subtype distribution using data from EUROCAT Northern Netherlands. We included all birth types with non-syndromal NTDs born in 1997-2012. By Fisher's exact test we analyzed possible differences in NTD subtype distribution between a correct FA supplementation group and incorrect FA supplementation group. We found proportionally fewer cervical/thoracic spina bifida cases and more lumbar/sacral spina bifida cases in the correct FA supplementation group, irrespective of the presence of the main NTD risk factors. The effect on NTD subtype distribution was only seen when FA supplementation was started before conception. We conclude that FA not only prevents the occurrence of a significant proportion of NTDs, but might also decrease the severity of NTDs, as long as supplementation is started before conception. PMID:26627544

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

    PubMed

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

    2014-10-15

    In this work, electrochemically synthesized gold nanoparticles (AuNPs) and α-polyoxometalate (α-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-α-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 0.3 V (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

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

    PubMed

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

    2015-08-01

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

  13. Preventive role of folic acid on the developmental toxicity of phenol in Drosophila melanogaster.

    PubMed

    Aşkin, H; Uysal, H; Altun, D

    2007-11-01

    Phenol (PN), obtained from coal tar, is used commonly in medical treatments, industrial areas, petroleum refineries, production of glue, fiber, and nylon. PN is used in the production of benzene and it is emitted in the atmosphere by motor vehicles. Folic acid (FA) is an essential nutrient among the B complex group of vitamins. The main aim of this study was to investigate the effects of PN and PN + FA on various developmental stages of Drosophila melanogaster. Different concentrations of PN and PN + FA were administered during the developmental periods of the fly (egg, larva and pupa). When F1 progeny of control and experimental groups were compared, PN was found to extend the process of metamorphosis and decrease the total offspring numbers. However, these negative effects were inhibited by FA treatment at different concentrations (0.25-2.50 mg/kg). These results suggest that FA could effectively inhibit PN-induced abnormalities in developmental stages of Drosophila melanogaster. PMID:18717517

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

    NASA Astrophysics Data System (ADS)

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

    2015-07-01

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

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

    PubMed Central

    2014-01-01

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

  16. Fabrication of poly hydroxybutyrate-polyethylene glycol-folic acid nanoparticles loaded by Paclitaxel.

    PubMed

    Rezaei, Fatemeh; Rafienia, Mohammad; Keshvari, Hamid; Sattary, Mansooreh; Naeimi, Mitra; Keyvani, Hossein

    2016-01-01

    In this study drug (paclitaxel)-loaded nanoparticles of poly hydroxybutyrate-polyethylene glycol-folic acid (PHB-PEG-FOL) were prepared by using an oil-in-water (O/W) emulsion-solvent evaporation method. The functionalization and conjugation steps in the chemical synthesis were confirmed using Fourier transform infrared (FTIR) and nuclear magnetic resonance tests ((1)H NMR). Morphology of nanoparticles was evaluated by scanning electron microscopy (SEM). Nanoparticles were characterized by particle size analyzer. Between two samples containing drug, the lower doses showed more homogeneous distribution, and the lowest aggregation. The drug release profiles showed a two-phase release including initial rapid release and a continuous release. MG63 cells were used to evaluate cytotoxicity. The cytotoxicity of PHB-PEG-FOL nanoparticles with drug against cancer cells was much higher and longer than free drug sample. These nanoparticles were successfully synthesized as a novel system for targeted drug delivery against cancer cells. PMID:26234551

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

    PubMed Central

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

    2012-01-01

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

  18. Folic-Acid-Modified Conducting Polymer: Electrochemical Detection of the Cell Attachment.

    PubMed

    Azak, Hacer; Barlas, Firat Baris; Yildiz, Huseyin Bekir; Gulec, Kadri; Demir, Bilal; Demirkol, Dilek Odaci; Timur, Suna

    2016-04-01

    Here, postfunctionalization and bioapplication of a π-conjugated polymer named 4-[4H-dithieno(3,2-b:2',3'-d)pyrrol-4-yl]aniline (DTP-aryl-NH2 ) are reported, which is successfully synthesized via electropolymerization onto the glassy carbon electrode. Folic acid (FA) is used to modify the amino functional polymer via N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide chemistry for the further steps. The selective adhesion of folate receptor positive cells on the surface is followed by the electrochemical methods. Cyclic voltammetry and electrochemical impedance spectroscopy have been used to characterize stepwise modification of the electroactive surface. After optimization studies such as scan rate during the polymer deposition, FA amount for the efficient surface targeting, incubation time with the cells etc., analytical characterization is carried out. The surface morphologies at each step are imaged by using fluorescence microscopy. PMID:26671168

  19. Folic acid supplements and risk for oral clefts in the newborn: a population-based study.

    PubMed

    Gildestad, Trude; Bjørge, Tone; Vollset, Stein Emil; Klungsøyr, Kari; Nilsen, Roy Miodini; Haaland, Øystein Ariansen; Øyen, Nina

    2015-11-14

    Results from previous studies on maternal folic acid intake and infant oral clefts are inconclusive. The aim of the present study was to investigate the association between women's use of folic acid and/or multivitamin supplements and the risk for oral cleft in the newborn. We used data from the Medical Birth Registry of Norway based on all births in Norway from 1999 to 2013. A total of 528 220 women had 880 568 pregnancies, resulting in 896 674 live births and stillbirths, of which 1623 had oral clefts (isolated oral clefts, n 1311; non-isolated oral clefts, n 312). Altogether, 21·5% of women were vitamin supplement users before pregnancy. The birth prevalence of oral clefts was 1·81/1000 live births and stillbirths. Relative risks (RR) were estimated with log-binomial regression. For pregnancies with maternal use of vitamins, the adjusted RR for clefts overall was 0·90 (95% CI 0·79, 1·04). The adjusted RR for cleft palate only (n 586) was 0·84 (95% CI 0·66, 1·06) and that for cleft lip with or without cleft palate (n 1037) was 0·94 (95% CI 0·79, 1·13). Associations were stronger for cleft cases that occurred in combination with other malformations (adjusted RR 0·63; 95% CI 0·45, 0·88), although vitamin supplements provided no protection against isolated clefts (adjusted RR 0·98; 95% CI 0·84, 1·15). In conclusion, our study demonstrates no statistically significant association between vitamin use and isolated oral clefts. However, we found lower risk for oral clefts that occurred in combination with other malformations. PMID:26343883

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

    PubMed Central

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

    2011-01-01

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

  1. Strong electrochemiluminescent interactions between carbon nitride nanosheet-reduced graphene oxide nanohybrids and folic acid, and ultrasensitive sensing for folic acid.

    PubMed

    Zhou, Chen; Chen, Yingmei; Shang, Pengxiang; Chi, Yuwu

    2016-05-23

    Graphite-like carbon nitride nanosheets (g-C3N4 NSs) have recently emerged as electrochemiluminescent (ECL) nanomaterials and have attracted more and more attention due to their excellent ECL properties and promising applications in ECL sensing. However, the ECL study of g-C3N4 NSs is still in the early stages. Many studies are required to reveal the exact ECL mechanisms of g-C3N4 NSs and thus boost their sensing applications. In this paper, we have investigated ECL interactions between folic acid (FA) and a g-C3N4 NS/S2O8(2-) ECL system at a g-C3N4 NS-reduced graphene oxide (rGO) nanohybrid/glassy carbon electrode in aqueous solutions. Compared with bare g-C3N4 NSs, the nanohybrids of g-C3N4 NS-rGO give a much stable ECL emission due to the prevention of over electrochemical reduction of g-C3N4 by rGO. The stable ECL emission from the g-C3N4 NS-rGO/S2O8(2-) ECL system can be strongly quenched by FA, even in a very low concentration (pM levels). The ECL quenching mechanisms are investigated and discussed in detail. Based on the strong interactions between FA and g-C3N4 NSs, a novel, sensitive, stable and selective ECL sensor has been constructed for the detection of FA, with a wide linear response range from 0.1 to 90 nM, and an excellent detection limit (62 pM). This work not only further clarifies ECL mechanisms of g-C3N4 NSs, but also suggests a promising application of the newly emerging ECL nanomaterial. PMID:27127810

  2. Neuroprotective Effects of Glutamate Antagonists and Extracellular Acidity

    NASA Astrophysics Data System (ADS)

    Kaku, David A.; Giffard, Rona G.; Choi, Dennis W.

    1993-06-01

    Glutamate antagonists protect neurons from hypoxic injury both in vivo and in vitro, but in vitro studies have not been done under the acidic conditions typical of hypoxia-ischemia in vivo. Consistent with glutamate receptor antagonism, extracellular acidity reduced neuronal death in murine cortical cultures that were deprived of oxygen and glucose. Under these acid conditions, N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-4-isox-azolepropionate-kainate antagonists further reduced neuronal death, such that some neurons tolerated prolonged oxygen and glucose deprivation almost as well as did astrocytes. Neuroprotection induced by this combination exceeded that induced by glutamate antagonists alone, suggesting that extracellular acidity has beneficial effects beyond the attenuation of ionotropic glutamate receptor activation.

  3. Non-covalent complexes of folic acid and oleic acid conjugated polyethylenimine: An efficient vehicle for antisense oligonucleotide delivery

    PubMed Central

    Yang, Shuang; Yang, Xuewei; Liu, Yan; Zheng, Bin; Meng, Lingjun; Lee, Robert J.; Xie, Jing; Teng, Lesheng

    2016-01-01

    Polyethylenimine (PEI) was conjugated to oleic acid (PEI-OA) and evaluated as a delivery agent for LOR-2501, an antisense oligonucleotide against ribonucleotide reductase R1 subunit. PEI-OA/LOR-2501 complexes were further coated with folic acid (FA/PEI-OA/LOR-2501) and evaluated in tumor cells. The level of cellular uptake of FA/PEI-OA/LOR-2501 was more than double that of PEI/LOR-2501 complexes, and was not affected by the expression level of folate receptor (FR) on the cell surface. Efficient delivery was seen in several cell lines. Furthermore, pathway specific cellular internalization inhibitors and markers were used to reveal the principal mechanism of cellular uptake. FA/PEI-OA/LOR-2501 significantly induced the downregulation of R1 mRNA and R1 protein. This novel formulation of FA/PEI-OA provides a reliable and highly efficient method for delivery of oligonucleotide and warrants further investigation. PMID:26263216

  4. Pre-conceptional intake of folic acid supplements is inversely associated with risk of preterm birth and small-for-gestational-age birth: a prospective cohort study.

    PubMed

    Zheng, Ju-Sheng; Guan, Yuhong; Zhao, Yimin; Zhao, Wei; Tang, Xuejuan; Chen, Hua; Xu, Meilong; Wu, Lingping; Zhu, Shanlin; Liu, Huijuan; Huang, Tao; Li, Duo

    2016-02-01

    Associations of folic acid supplementation with risk of preterm birth (PTB) and small-for-gestational-age (SGA) birth were unclear for the Chinese populations. The aim of the present study was to investigate the associations in a large Chinese prospective cohort study: the Jiaxing Birth Cohort. In the Jiaxing Birth Cohort, 240 954 pregnant women visited local clinics or hospitals within their first trimester in Southeast China during 1999-2012. Information on anthropometric parameters, folic acid supplementation and other maternal characteristics were collected by in-person interviews during their first visit. Pregnancy outcomes were recorded during the follow-up of these participants. Multinomial logistic regression was used to examine the association of folic acid supplementation with pregnancy outcomes. The prevalence of folic acid supplementation was 249 % in the cohort. The prevalence of PTB and SGA birth was 348 and 92 %, respectively. Pre-conceptional folic acid supplementation was associated with 8 % lower risk of PTB (relative risk (RR) 092; 95 % CI 085, 100; P=004) and 19 % lower risk of SGA birth (RR 081; 95 % CI 070, 095; P=0008), compared with non-users. Higher frequency of pre-conceptional folic acid use was associated with lower risk of PTB (P trend=0032) and SGA birth (P trend=0046). No significant association between post-conceptional initiation of folic acid supplementation and either outcome was observed. In conclusion, the present study suggests an association between pre-conceptional, but not post-conceptional, folic acid supplementation and lower risk of PTB and SGA birth in the Jiaxing Birth Cohort. Further research in other cohorts of large sample size is needed to replicate these findings. PMID:26651997

  5. Decreased TGF-beta1 and IGF-1 protein expression in rat embryo skull bone in folic acid-restricted diet.

    PubMed

    Santoso, Mochammad Istiadjid Eddy; Rohman, Mohammad Saifur

    2006-01-01

    Folic acid deficiency during conception up to the end of the third month of gestation is believed to play the most important factor in neural tube defects (NTDs). However, the exact molecular mechanism remains to be elucidated. It has been suggested that transforming growth factor-beta (TGF-beta1) and insulin-like growth factor-1 (IGF-1) play a critical role in supporting bone formation. Therefore, folic acid deficiency may contribute to NTD occurrence via decreased TGF-beta1 and IGF-1 expression. This study aimed to determine the correlation between folic acid deficiency and the expression of TGF-beta1 and IGF-1 in rat skull bone. Thirty female Sprague-Dawley rats were divided into three groups. Purified diet containing 5 (restricted), 15 (low) and 30 microg (normal) of folic acid was given to the first, second and third groups, respectively. At 16 weeks of a given diet, blood samples were taken to examine folic acid (folate immunoassay method), TGF-beta1 and IGF-1 (enzyme-linked immunosorbent assay method) levels. After forced mating, on the 18th-19th day of gestation (E18-19), the pregnant rats were subjected to hysterectomy. The skull bone samples of E18-19 rats were taken to examine the TGF-beta1 and IGF-1 protein expression by immunohistochemistry. The folic acid-restricted diet (5 microg) resulted in decreased serum TGF-beta1 and IGF-1 levels. Furthermore, protein expression of TGF-beta1 and IGF-1 in E18-19 rat skull bones was also significantly lower in the folic acid-restricted diet than in the normal diet. Folic acid deficiency could result in reduction of TGF-beta1 and IGF-1 protein levels and might contribute to formation of defects in the skull bone as observed in mengingocele patients. PMID:16111879

  6. A Combined Supplementation of Omega-3 Fatty Acids and Micronutrients (Folic Acid, Vitamin B12) Reduces Oxidative Stress Markers in a Rat Model of Pregnancy Induced Hypertension

    PubMed Central

    Kemse, Nisha G.; Kale, Anvita A.; Joshi, Sadhana R.

    2014-01-01

    Objectives Our earlier studies have highlighted that an altered one carbon metabolism (vitamin B12, folic acid, and docosahexaenoic acid) is associated with preeclampsia. Preeclampsia is also known to be associated with oxidative stress and inflammation. The current study examines whether maternal folic acid, vitamin B12 and omega-3 fatty acid supplementation given either individually or in combination can ameliorate the oxidative stress markers in a rat model of pregnancy induced hypertension (PIH). Materials and Methods Pregnant Wistar rats were assigned to control and five treatment groups: PIH; PIH + vitamin B12; PIH + folic acid; PIH + Omega-3 fatty acids and PIH + combined micronutrient supplementation (vitamin B12 + folic acid + omega-3 fatty acids). L-Nitroarginine methylester (L-NAME; 50 mg/kg body weight/day) was used to induce hypertension during pregnancy. Blood Pressure (BP) was recorded during pregnancy and dams were dissected at d20 of gestation. Results Animals from the PIH group demonstrated higher (p<0.01 for both) systolic and diastolic BP; lower (p<0.01) pup weight; higher dam plasma homocysteine (p<0.05) and dam and offspring malondialdehyde (MDA) (p<0.01), lower (p<0.05) placental and offspring liver DHA and higher (p<0.01) tumor necrosis factor–alpha (TNF–ά) levels as compared to control. Individual micronutrient supplementation did not offer much benefit. In contrast, combined supplementation lowered systolic BP, homocysteine, MDA and placental TNF-ά levels in dams and liver MDA and protein carbonyl in the offspring as compared to PIH group. Conclusion Key constituents of one carbon cycle (folic acid, vitamin B12 and DHA) may play a role in reducing oxidative stress and inflammation in preeclampsia. PMID:25405347

  7. A combination of omega-3 fatty acids, folic acid and B-group vitamins is superior at lowering homocysteine than omega-3 alone: A meta-analysis.

    PubMed

    Dawson, Samantha Loren; Bowe, Steven John; Crowe, Timothy Charles

    2016-06-01

    The aim of the study was to assess whether omega-3 polyunsaturated fatty acid supplementation alone or in combination with folic acid and B-group vitamins is effective in lowering homocysteine. The Medline Ovid, Embase and Cochrane databases were searched for randomized-controlled trial studies that intervened with omega-3 supplementation (with or without folic acid) and measured changes in homocysteine concentration. Studies were pooled using a random effects model for meta-analysis. Three different models were analyzed: all trials combined, omega-3 polyunsaturated fatty acid trials, and omega-3 polyunsaturated fatty acids with folic acid and B-group vitamin trials. Nineteen studies were included, consisting of 3267 participants completing 21 trials. Studies were heterogeneous; varying by dose, duration and participant health conditions. Across all trials, omega-3 supplementation was effective in lowering homocysteine by an average of 1.18μmol/L (95%CI: (-1.89, -0.48), P=.001). The average homocysteine-lowering effect was greater when omega-3 supplementation was combined with folic acid and B-group vitamins (-1.37μmol/L, 95%CI: (-2.38, -0.36), P<.01) compared to omega-3 supplementation alone (-1.09μmol/L 95%CI: (-2.04, -0.13), P=.03). Omega-3 polyunsaturated fatty acid supplementation was associated with a modest reduction in homocysteine. For the purposes of reducing homocysteine, a combination of omega-3s (0.2-6g/day), folic acid (150 - 2500μg/day) and vitamins B6 and B12 may be more effective than omega-3 supplementation alone. PMID:27188895

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

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

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

  9. Electrochemical determination of hydrochlorothiazide and folic acid in real samples using a modified graphene oxide sheet paste electrode.

    PubMed

    Beitollahi, Hadi; Hamzavi, Mozhdeh; Torkzadeh-Mahani, Masoud

    2015-01-01

    A new ferrocene-derivative compound, 2-chlorobenzoyl ferrocene, was synthesized and used to construct a modified graphene oxide sheet paste electrode. The electrooxidation of hydrochlorothiazide at the surface of the modified electrode was studied. Under optimized conditions, the square wave voltammetric (SWV) peak current of hydrochlorothiazide increased linearly with hydrochlorothiazide concentration in the range of 5.0 × 10(-8) to 2.0 × 10(-4) M and a detection limit of 20.0 nM was obtained for hydrochlorothiazide. The diffusion coefficient and kinetic parameters (such as electron transfer coefficient and the heterogeneous rate constant) for hydrochlorothiazide oxidation were also determined. The prepared modified electrode exhibits a very good resolution between the voltammetric peaks of hydrochlorothiazide and folic acid which makes it suitable for the detection of hydrochlorothiazide in the presence of folic acid in real samples. PMID:25953571

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

    PubMed

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

    2011-04-01

    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 (2 mm × 100 mm, 1.5 μm). After selection of the stationary phase, the method was further optimised by testing two aqueous and two organic phases and by adapting to a gradient method. The obtained method was fully validated based on its measurement uncertainty (accuracy profile) and robustness tests. A UHPLC method was obtained for the identification and quantification of folic acid in pharmaceutical preparations, which will cut analysis times and solvent consumption. PMID:21168299

  11. Folic Acid Improves Acetylcholine-induced Vasoconstriction of Coronary Vessels Isolated from hyperhomocysteinemic mice: An Implication to Coronary Vasospasm*

    PubMed Central

    Qipshidze, Natia; Metreveli, Naira; Lominadze, David; Tyagi, Suresh C.

    2011-01-01

    Human atherosclerotic coronary vessels elicited vasoconstriction to acetylcholine (Ach) and revealed a phenomenon of vasospasm. Homocysteine (Hcy) levels are elevated in the atherosclerotic plaque tissue, suggesting its pathological role in endothelial damage in atherosclerotic diseases. Accordingly, we examined the role hyperhomocysteinemia (HHcy) in coronary endothelial dysfunction, vessel wall thickness, lumen narrowing, leading to acute/chronic coronary vasospasm. The therapeutic potential and mechanisms of folic acid using hyperhomocysteinemic cystathionine beta synthase heterozygote (CBS-/+) and wild type (CBS+/+) mice were addressed. The CBS-/+ and CBS+/+ mice were treated with or without a Hcy lowering agent folic acid (FA) in drinking water (0.03 g/L) for 4 weeks. The isolated mouse septum coronary artery was cannulated and pressurized at 60 mmHg. The wall thickness and lumen diameters were measured by Ion-Optic. The vessels were treated with Ach (10-8-10-5 M) and, for comparison, with nonendothelial vasodilator sodium nitroprusside (10-5 M).The endothelium-impaired arteries from CBC-/+ mice constricted in response to Ach and this vasoconstriction was mitigated with FA supplementation. The level of endothelial nitric oxide synthase (eNOS) was lower in coronary artery in CBS-/+ than of CBS+/+ mice. Treatment with FA increased the levels of Ach-induced NO generation in the coronary artery of CBS-/+ mice. The results suggest that Ach induced coronary vasoconstriction in CBS-/+ mice and this vasoconstriction was ameliorated by folic acid treatment. The mechanisms for the impairment of vascular function and therapeutic effects of folic acid may be related to the regulation of eNOS expression, NO availability and tissue homocysteine. PMID:21792928

  12. Hybrid molecularly imprinted poly(methacrylic acid-TRIM)-silica chemically modified with (3-glycidyloxypropyl)trimethoxysilane for the extraction of folic acid in aqueous medium.

    PubMed

    de Oliveira, Fernanda Midori; Segatelli, Mariana Gava; Tarley, César Ricardo Teixeira

    2016-02-01

    In the present study a hybrid molecularly imprinted poly(methacrylic acid-trimethylolpropane trimethacrylate)-silica (MIP) was synthesized and modified with (3-glycidyloxypropyl)trimethoxysilane (GPTMS) with posterior opening of epoxy ring to provide hydrophilic properties of material in the extraction of folic acid from aqueous medium. The chemical and structural aggregates of hybrid material were characterized by means of Fourier Transform Infrared (FT-IR), Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), Thermogravimetric analysis (TGA) and textural data. Selectivity data of MIP were compared to non-imprinted polymer (NIP) through competitive sorption studies in the presence of caffeine, paracetamol or 4-aminobenzamide yielding relative selectivity coefficients (k′) higher than one unit, thus confirming the selective character of MIP even in the presence of structurally smaller compounds than the folic acid. The lower hydrophobic sorption by bovine serum albumin (BSA) in the MIP as compared to unmodified MIP proves the hydrophilicity of polymer surface by using GPTMS with opening ring. Under acid medium(pH 1.5) the sorption of folic acid onto MIP from batch experiments was higher than the one achieved for NIP. Equilibrium sorption of folic acid was reached at 120 min for MIP, NIP and MIP without GPTMS and kinetic sorption data were well described by pseudo-second-order, Elovich and intraparticle diffusion models. Thus, these results indicate the existence of different binding energy sites in the polymers and a complex mechanism consisting of both surface sorption and intraparticle transport of folic acid within the pores of polymers. PMID:26652418

  13. DNA methylation in Folbp1 knockout mice supplemented with folic acid during gestation.

    PubMed

    Finnell, Richard H; Spiegelstein, Ofer; Wlodarczyk, Bogdan; Triplett, Aleata; Pogribny, Igor P; Melnyk, Stepan; James, Jill S

    2002-08-01

    Periconceptional folic acid supplementation has been shown to prevent up to 70% of neural tube and other birth defects in humans; however, the mechanism is still unknown. In this study, we tested whether defective intracellular folate transport, as achieved by inactivation of the murine folate-binding protein 1 (Folbp1), affects global DNA methylation in the liver and brain from gestational day (GD) 15 embryos. Complete Folbp1 inactivation is embryolethal but can be reversed by maternal folinic acid (FA) supplementation, and thus we also tested the effect of FA supplementation on DNA methylation in Folbp1 fetuses. Overall, the extent of global DNA methylation seems to be similar across all genotypes in unsupplemented control Folbp1 mice; however, explicit conclusions regarding Folbp1(-/-) fetuses were not possible because only a single living unsupplemented fetus was viable at GD 15. FA supplementation induced global DNA hypomethylation across all genotypes. FA-induced hypomethylation is most likely due to its ability to inhibit the enzyme glycine hydroxymethyltransferase, thereby inhibiting the homocysteine remethylation cycle necessary to regenerate S-adenosylmethionine, the methyl donor for DNA methyltransferases. Our hypothesis was that due to defective folate transport in Folbp1(-/-) embryos and fetuses, DNA would be hypomethylated, thereby altering the temporal expression of critical genes necessary for normal embryonic development. However, these results suggest that an extended examination of changes in DNA methylation prior to GD 15 is required to unequivocally prove or disprove the hypothesis. PMID:12163711

  14. LC/MS/MS identification of some folic acid degradation products after E-beam irradiation

    NASA Astrophysics Data System (ADS)

    Araújo, M. M.; Marchioni, E.; Zhao, M.; Kuntz, F.; Di Pascoli, T.; Villavicencio, A. L. C. H.; Bergaentzle, M.

    2012-08-01

    Folates belong to the B vitamin group based on the parental compound folic acid (FA). They are involved in important biochemical processes like DNA synthesis and repair. FA is composed of a pteridine ring, p-aminobenzoic acid and glutamate moieties. The human metabolism is not able to synthesize folates and therefore obtain them from diet. FA, a synthetic vitamin, is used as a food fortificant because of its low price, relative stability and increased bioavailability compared to natural folate forms. FA is known to be a sensitive compound easily degradable in aqueous solution by ultraviolet and visible light towards various by-products. Irradiation is a process for preservation of foods that uses accelerated electrons, gamma rays or X-rays. Irradiation is proposed for the treatment of various food products, eliminating or reducing pathogens and insects, increasing the storage time and replacing chemical fumigants. This study concerns the identification of degradation products of FA after E-beam irradiation. FA aqueous solutions were irradiated with a Van de Graaff electrons beam accelerator (2 MeV, 100 μA current, 20 cm scan width, dose rate about 2 kGy/s). Applied doses were between 0 (control) and 10.0 kGy. Absorbed doses were monitored with FWT 60.00 radiochromic dosimeters.

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

    PubMed

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

    2015-07-27

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

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

    PubMed Central

    2011-01-01

    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 (μg/d) for adult pregnant women. The primary objective is to estimate the proportion of women taking folic acid (FA) doses exceeding the TUL before and during pregnancy, and to identify correlates of high FA use. Methods During 2005-2008, pre-pregnancy and pregnancy-related data on dietary supplementation were obtained by interviewing 539 pregnant women enrolled at two obstetrics-care facilities in Durham County, North Carolina. Results Before pregnancy, 51% of women reported FA supplementation and 66% reported this supplementation during pregnancy. Before pregnancy, 11.9% (95% CI = 9.2%-14.6%) of women reported supplementation with FA doses above the TUL of 1,000 μg/day, and a similar proportion reported this intake prenatally. Before pregnancy, Caucasian women were more likely to take FA doses above the TUL (OR = 2.99; 95% = 1.28-7.00), compared to African American women, while women with chronic conditions were less likely to take FA doses above the TUL (OR = 0.48; 95%CI = 0.21-0.97). Compared to African American women, Caucasian women were also more likely to report FA intake in doses exceeding the TUL during pregnancy (OR = 5.09; 95%CI = 2.07-12.49). Conclusions Fifty-one percent of women reported some FA intake before and 66% during pregnancy, respectively, and more than one in ten women took FA supplements in doses that exceeded the TUL. Caucasian women were more likely to report high FA intake. A study is ongoing to identify possible genetic and non-genotoxic effects of these high doses. PMID:21255390

  17. Treatment of depression: time to consider folic acid and vitamin B12.

    PubMed

    Coppen, Alec; Bolander-Gouaille, Christina

    2005-01-01

    We review the findings in major depression of a low plasma and particularly red cell folate, but also of low vitamin B12 status. Both low folate and low vitamin B12 status have been found in studies of depressive patients, and an association between depression and low levels of the two vitamins is found in studies of the general population. Low plasma or serum folate has also been found in patients with recurrent mood disorders treated by lithium. A link between depression and low folate has similarly been found in patients with alcoholism. It is interesting to note that Hong Kong and Taiwan populations with traditional Chinese diets (rich in folate), including patients with major depression, have high serum folate concentrations. However, these countries have very low life time rates of major depression. Low folate levels are furthermore linked to a poor response to antidepressants, and treatment with folic acid is shown to improve response to antidepressants. A recent study also suggests that high vitamin B12 status may be associated with better treatment outcome. Folate and vitamin B12 are major determinants of one-carbon metabolism, in which S-adenosylmethionine (SAM) is formed. SAM donates methyl groups that are crucial for neurological function. Increased plasma homocysteine is a functional marker of both folate and vitamin B12 deficiency. Increased homocysteine levels are found in depressive patients. In a large population study from Norway increased plasma homocysteine was associated with increased risk of depression but not anxiety. There is now substantial evidence of a common decrease in serum/red blood cell folate, serum vitamin B12 and an increase in plasma homocysteine in depression. Furthermore, the MTHFR C677T polymorphism that impairs the homocysteine metabolism is shown to be overrepresented among depressive patients, which strengthens the association. On the basis of current data, we suggest that oral doses of both folic acid (800 microg daily) and vitamin B12 (1 mg daily) should be tried to improve treatment outcome in depression. PMID:15671130

  18. Effect of long-term supplementation with folic acid and B vitamins on risk of depression in older women

    PubMed Central

    Okereke, Olivia I.; Cook, Nancy R.; Albert, Christine M.; Van Denburgh, Martin; Buring, Julie E.; Manson, JoAnn E.

    2015-01-01

    Background Homocysteine-lowering nutrients may have preventive/ameliorative roles in depression. Aims To test whether long-term B-vitamin/folate supplementation reduces depression risk. Method Participants were 4331 women (mean age 63.6 years), without prior depression, from the Women’s Antioxidant and Folic Acid Cardiovascular Study – a randomised controlled trial of cardiovascular disease prevention among 5442 women. 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 a matching placebo. Average treatment duration was 7 years. The outcome was incident depression, defined as self-reported physician/clinician-diagnosed depression or clinically significant depressive symptoms. Results There were 524 incident cases. There was no difference between active v. placebo groups in depression risk (adjusted relative risk 1.02, 95% CI 0.86–1.21, P = 0.81), despite significant homocysteine level reduction. Conclusions Long-term, high-dose, daily supplementation with folic acid and vitamins B6 and B12 did not reduce overall depression risk in mid-life and older women. PMID:25573400

  19. Effectiveness of Folic Acid Fortified Flour for Prevention of Neural Tube Defects in a High Risk Region

    PubMed Central

    Wang, Haochen; De Steur, Hans; Chen, Gong; Zhang, Xiaotian; Pei, Lijun; Gellynck, Xavier; Zheng, Xiaoying

    2016-01-01

    Despite efforts to tackle folate deficiency and Neural Tube Defects (NTDs) through folic acid fortification, its implementation is still lacking where it is needed most, highlighting the need for studies that evaluate the effectiveness of folic acid fortified wheat flour in a poor, rural, high-risk, NTD region of China. One of the most affected regions, Shanxi Province, was selected as a case study. A community intervention was carried out in which 16,648 women of child-bearing age received fortified flour (eight villages) and a control group received ordinary flour (three villages). NTD birth prevalence and biological indicators were measured two years after program initiation at endline only. The effect on the NTD burden was calculated using the disability-adjusted life years (DALYs) method. In the intervention group, serum folate level was higher than in the control group. NTDs in the intervention group were 68.2% lower than in the control group (OR = 0.313, 95% CI = 0.207–0473, p < 0.001). In terms of DALYs, burden in intervention group was approximately 58.5% lower than in the control group. Flour fortification was associated with lower birth prevalence and burden of NTDs in economically developing regions with a high risk of NTDs. The positive findings confirm the potential of fortification when selecting an appropriate food vehicle and target region. As such, this study provides support for decision makers aiming for the implementation of (mandatory) folic acid fortification in China. PMID:27005659

  20. Effectiveness of Folic Acid Fortified Flour for Prevention of Neural Tube Defects in a High Risk Region.

    PubMed

    Wang, Haochen; De Steur, Hans; Chen, Gong; Zhang, Xiaotian; Pei, Lijun; Gellynck, Xavier; Zheng, Xiaoying

    2016-01-01

    Despite efforts to tackle folate deficiency and Neural Tube Defects (NTDs) through folic acid fortification, its implementation is still lacking where it is needed most, highlighting the need for studies that evaluate the effectiveness of folic acid fortified wheat flour in a poor, rural, high-risk, NTD region of China. One of the most affected regions, Shanxi Province, was selected as a case study. A community intervention was carried out in which 16,648 women of child-bearing age received fortified flour (eight villages) and a control group received ordinary flour (three villages). NTD birth prevalence and biological indicators were measured two years after program initiation at endline only. The effect on the NTD burden was calculated using the disability-adjusted life years (DALYs) method. In the intervention group, serum folate level was higher than in the control group. NTDs in the intervention group were 68.2% lower than in the control group (OR = 0.313, 95% CI = 0.207-0473, p < 0.001). In terms of DALYs, burden in intervention group was approximately 58.5% lower than in the control group. Flour fortification was associated with lower birth prevalence and burden of NTDs in economically developing regions with a high risk of NTDs. The positive findings confirm the potential of fortification when selecting an appropriate food vehicle and target region. As such, this study provides support for decision makers aiming for the implementation of (mandatory) folic acid fortification in China. PMID:27005659

  1. The folic acid analogue methotrexate protects frog embryo cell membranes against damage by the potato glycoalkaloid alpha-chaconine.

    PubMed

    McWilliams, M L; Blankemeyer, J T; Friedman, M

    2000-10-01

    As part of an effort to improve the safety of plant foods, a need exists to more clearly delineate the mechanisms of toxicities of glycoalkaloids, which may be present in Solanum plant species such as potatoes, tomatoes and eggplants. Alpha-chaconine is a major glycoalkaloid present in potatoes. To assess the possible influence of structure of pteridine derivatives on toxicity of potato glycoalkaloids, a previous study that demonstrated the protective effects of folic acid against the Solanum glycoalkaloid alpha-chaconine-induced toxicity on Xenopus laevis frog embryo cell membranes was extended to two folate analogues--a synthetic compound widely used as a therapeutic agent methotrexate, and naturally occurring L-monapterin. Adverse effects on embryos were evaluated by observing changes in membrane potentials with an electrochromic dye, di-4-ANEPPS, as a fluorescent probe for the integrity of the membranes. Methotrexate decreased alpha-chaconine-induced polarization, as did folic acid. This decrease may result from an alteration of membrane conformations that prevents the binding of the glycoalkaloid to the membrane receptor sites, and/or from effects on folic acid metabolism. In contrast, L-monapterin did not significantly reduce the alpha-chaconine-induced toxicity. The possible significance of these results to food safety is discussed. PMID:11039318

  2. DNA Methylation Profiling at Single-Base Resolution Reveals Gestational Folic Acid Supplementation Influences the Epigenome of Mouse Offspring Cerebellum

    PubMed Central

    Barua, Subit; Kuizon, Salomon; Brown, W. Ted; Junaid, Mohammed A.

    2016-01-01

    It is becoming increasingly more evident that lifestyle, environmental factors, and maternal nutrition during gestation can influence the epigenome of the developing fetus and thus modulate the physiological outcome. Variations in the intake of maternal nutrients affecting one-carbon metabolism may influence brain development and exert long-term effects on the health of the progeny. In this study, we investigated whether supplementation with high maternal folic acid during gestation alters DNA methylation and gene expression in the cerebellum of mouse offspring. We used reduced representation bisulfite sequencing to analyze the DNA methylation profile at the single-base resolution level. The genome-wide DNA methylation analysis revealed that supplementation with higher maternal folic acid resulted in distinct methylation patterns (P < 0.05) of CpG and non-CpG sites in the cerebellum of offspring. Such variations of methylation and gene expression in the cerebellum of offspring were highly sex-specific, including several genes of the neuronal pathways. These findings demonstrate that alterations in the level of maternal folic acid during gestation can influence methylation and gene expression in the cerebellum of offspring. Such changes in the offspring epigenome may alter neurodevelopment and influence the functional outcome of neurologic and psychiatric diseases. PMID:27199632

  3. Folic acid conjugated mPEG-PEI600 as an efficient non-viral vector for targeted nucleic acid delivery.

    PubMed

    Xu, Zhenhua; Jin, Jiefu; Siu, Leo K S; Yao, Hong; Sze, Johnny; Sun, Hongzhe; Kung, Hsiang-Fu; Poon, Wai Sang; Ng, Samuel S M; Lin, Marie C

    2012-04-15

    In this study we describe a novel polymer, mPPS-FA, synthesized as a potential gene transfer vector. To complete mPPS-FA, folic acid was conjugated to a backbone (named mPPS) consisting of a copolymer of methyl PEG-2000, PEI-600, and sebacoyl chloride. (1)H NMR, FT-IR, and UV spectroscopy were used to characterize the structure of mPPS-FA. It was revealed that mPPS-FA holds the ability to bind plasmid DNA yielding positively charged particles (polyplexes). Dynamic light scattering (DLS) and TEM techniques were used to study the size and morphology of the formed mPPS-FA/DNA nanocomplexes. The mPPS-FA/DNA nanoparticles exhibited low cytotoxicity as transfection of B16-F0, U87MG, CHO-1, and Ho-8910 cells produced >80% viability indicating low cytotoxicity of the polymer. The ability of mPPS-FA to deliver EGFP plasmid to melanoma B16-F0, U87, CHO-1, Ho-8910, and A549 cells was investigated in vitro as compared to the lipid-based transfection agent Lipofectamine2000 and Linear PEI 22 kDa (L-PEI 22 kDa). We found that mPPS-FA/DNA complexes yielded the highest GFP transfection efficiency in B16-F0, U87, CHO-1, and Ho-8910 cells, which all highly express folate receptors (FR), at an mPPS-FA/DNA ratio (w/w) of 15. Furthermore, the transfection of mPPS-FA/DNA complexes in CHO-1 cells could be competitively blocked by free folic acid molecules. In contrast, in low FR expressing A549 cells, mPPS-FA showed similar low transfection efficiency as mPPS. Taken together, mPPS-FA showed the highest efficiency in vitro and the potential to be developed as a nonviral gene carrier. PMID:22265912

  4. [Age-associated changes in the metabolism of vitamin B(12) and folic acid: prevalence, aetiopathogenesis and pathophysiological consequences].

    PubMed

    Wolters, M; Ströhle, A; Hahn, A

    2004-04-01

    The increasing number of older people is characteristic for most industrialised nations and implicates the known psychosocial and economic consequences. Therefore, an optimal nutrient supply that promotes continuing mental and physical well-being is particularly important. In this respect, vitamin B(12) and folic acid play a major role, since deficiency of both vitamins is associated with the pathogenesis of different diseases such as declining neurocognitive function and atherosclerotic lesions. Vitamin B(12) and folic acid act as coenzymes and show a close molecular interaction on the basis of the homocysteine metabolism. In addition to the serum concentrations of the vitamins, the metabolites homocysteine and methylmalonic acid are sensitive markers of cobalamin and folate status. Depending on the used marker, 3-60% of the elderly are classified as vitamin B(12) deficient and about 29% as folate deficient. Predominantly, this high prevalence of poor cobalamin status is caused by the increasing prevalence of atrophic gastritis type B, which occurs with a frequency of approximately 20-50% in elderly subjects. Atrophic gastritis results in declining gastric acid and pepsinogen secretion, and hence decreasing intestinal digestion and absorption of both B vitamins. This is the reason why an insufficient vitamin B(12) status in the elderly is rarely due to low dietary intake. In contrast, folic acid intake among elderly subjects is generally well below the recommended dietary reference values. Even moderately increased homocysteine levels or poor folate and vitamin B(12) status are associated with vascular disease and neurocognitive disorders. Results of a meta-analysis of prospective studies revealed that a 25% lower homocysteine level (about 3 micromol/L) was associated with an 11% lower ischemic heart disease risk and 19% lower stroke risk. It is still discussed, whether hyperhomocysteinemia is causally related to vascular disease or whether it is a consequence of atherosclerosis. Estimated risk reduction is based on cohort studies, not on clinical trials. Homocysteine initiates different proatherogenetic mechanisms such as the formation of reactive oxygen species and an enhanced fibrin synthesis. Supplementation of folic acid (0.5-5 mg/d) reduces the homocysteine concentration by 25%. Additional vitamin B(12) (0.5 mg/d) induces further reduction by 7%. In secondary prevention, supplementation already led to clinical improvements (reduction of restenosis rate and plaques). Depression, dementia, and mental impairment are often associated with folate and vitamin B(12) deficiency. The biochemical reason of this finding may be the importance of folic acid and vitamin B(12) for the transmethylation of neuroactive substances (myelin, neurotransmitters) which is impaired in vitamin deficiency ("hypomethylation hypothesis"). In recent years, there is increasing evidence for a role of folic acid in cancer prevention. As a molecular mechanism of a preventive effect of folic acid the hypomethylation of certain DNA sections in folate deficiency has been suggested. Since folate and vitamin B(12) intake and status are mostly insufficient in elderly subjects, a supplementation can generally be recommended. PMID:15103481

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

    PubMed

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

    2010-05-01

    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

  6. Unmetabolized Folic Acid Is Detected in Nearly All Serum Samples from US Children, Adolescents, and Adults1234

    PubMed Central

    Pfeiffer, Christine M; Sternberg, Maya R; Fazili, Zia; Yetley, Elizabeth A; Lacher, David A; Bailey, Regan L; Johnson, Clifford L

    2015-01-01

    Background: Serum total folate consists mainly of 5-methyltetrahydrofolate (5-methylTHF). Unmetabolized folic acid (UMFA) may occur in persons consuming folic acidfortified foods or supplements. Objectives: We describe serum 5-methylTHF and UMFA concentrations in the US population ?1 y of age by demographic variables and fasting time, stratified by folic acidcontaining dietary supplement use. We also evaluate factors associated with UMFA concentrations >1 nmol/L. Methods: Serum samples from the cross-sectional NHANES 20072008 were measured for 5-methylTHF (n = 2734) and UMFA (n = 2707) by HPLCtandem mass spectrometry. Results: In supplement users compared with nonusers, we found significantly higher geometric mean concentrations of 5-methylTHF (48.4 and 30.7 nmol/L, respectively) and UMFA (1.54 and 0.794 nmol/L, respectively). UMFA concentrations were detectable (>0.3 nmol/L) in >95% of supplement users and nonusers, regardless of demographic or fasting characteristics; concentrations differed significantly by age and fasting time, but not by sex and race-ethnicity, both in supplement users and nonusers. The prevalence of UMFA concentrations >1 nmol/L was 33.2% overall and 21.0% in fasting (?8 h) adults (?20 y of age). Using multiple logistic regression analysis, UMFA concentrations >1 nmol/L were associated with being older, non-Hispanic black, nonfasting (<8 h), having smaller body surface area, higher total folic acid intake (diet and supplements), and higher red blood cell folate concentrations. In fasting adults, a decrease in the mean daily alcohol consumption was also associated with increased odds of UMFA concentrations >1 nmol/L. Conclusions: UMFA detection was nearly ubiquitous, and concentrations >1 nmol/L were largely but not entirely explained by fasting status and by total folic acid intake from diet and supplements. These new UMFA data in US persons ?1 y of age provide much-needed information on this vitamer in a fortified population with relatively high use of dietary supplements. PMID:25733468

  7. Folate Catabolites in Spot Urine as Non-Invasive Biomarkers of Folate Status during Habitual Intake and Folic Acid Supplementation

    PubMed Central

    Niesser, Mareile; Demmelmair, Hans; Weith, Thea; Moretti, Diego; Rauh-Pfeiffer, Astrid; van Lipzig, Marola; Vaes, Wouter; Koletzko, Berthold; Peissner, Wolfgang

    2013-01-01

    Background Folate status, as reflected by red blood cell (RCF) and plasma folates (PF), is related to health and disease risk. Folate degradation products para-aminobenzoylglutamate (pABG) and para-acetamidobenzoylglutamate (apABG) in 24 hour urine have recently been shown to correlate with blood folate. Aim Since blood sampling and collection of 24 hour urine are cumbersome, we investigated whether the determination of urinary folate catabolites in fasted spot urine is a suitable non-invasive biomarker for folate status in subjects before and during folic acid supplementation. Study Design and Methods Immediate effects of oral folic acid bolus intake on urinary folate catabolites were assessed in a short-term pre-study. In the main study we included 53 healthy men. Of these, 29 were selected for a 12 week folic acid supplementation (400 µg). Blood, 24 hour and spot urine were collected at baseline and after 6 and 12 weeks and PF, RCF, urinary apABG and pABG were determined. Results Intake of a 400 µg folic acid bolus resulted in immediate increase of urinary catabolites. In the main study pABG and apABG concentrations in spot urine correlated well with their excretion in 24 hour urine. In healthy men consuming habitual diet, pABG showed closer correlation with PF (rs = 0.676) and RCF (rs = 0.649) than apABG (rs = 0.264, ns and 0.543). Supplementation led to significantly increased folate in plasma and red cells as well as elevated urinary folate catabolites, while only pABG correlated significantly with PF (rs = 0.574) after 12 weeks. Conclusion Quantification of folate catabolites in fasted spot urine seems suitable as a non-invasive alternative to blood or 24 hour urine analysis for evaluation of folate status in populations consuming habitual diet. In non-steady-state conditions (folic acid supplementation) correlations between folate marker (RCF, PF, urinary catabolites) decrease due to differing kinetics. PMID:23457526

  8. Pathway of cytotoxicity induced by folic acid modified selenium nanoparticles in MCF-7 cells.

    PubMed

    Pi, Jiang; Jin, Hua; Liu, Ruiying; Song, Bing; Wu, Qing; Liu, Li; Jiang, Jinhuan; Yang, Fen; Cai, Huaihong; Cai, Jiye

    2013-02-01

    Selenium nanoparticles (Se NPs) have been recognized as promising materials for biomedical applications. To prepare Se NPs which contained cancer targeting methods and to clarify the cellular localization and cytotoxicity mechanisms of these Se NPs against cancer cells, folic acid protected/modified selenium nanoparticles (FA-Se NPs) were first prepared by a one-step method. Some morphologic and spectroscopic methods were obtained to prove the successfully formation of FA-Se NPs while free folate competitive inhibition assay, microscope, and several biological methods were used to determine the in vitro uptake, subcellular localization, and cytotoxicity mechanism of FA-Se NPs in MCF-7 cells. The results indicated that the 70-nm FA-Se NPs were internalized by MCF-7 cells through folate receptor-mediated endocytosis and targeted to mitochondria located regions through endocytic vesicles transporting. Then, the FA-Se NPs entered into mitochondria; triggered the mitochondria-dependent apoptosis of MCF-7 cells which involved oxidative stress, Ca(2)+ stress changes, and mitochondrial dysfunction; and finally caused the damage of mitochondria. FA-Se NPs released from broken mitochondria were transported into nucleus and further into nucleolus which then induced MCF-7 cell cycle arrest. In addition, FA-Se NPs could induce cytoskeleton disorganization and induce MCF-7 cell membrane morphology alterations. These results collectively suggested that FA-Se NPs could be served as potential therapeutic agents and organelle-targeted drug carriers in cancer therapy. PMID:22945264

  9. High fidelity information processing in folic acid chemotaxis of Dictyostelium amoebae.

    PubMed

    Segota, Igor; Mong, Surin; Neidich, Eitan; Rachakonda, Archana; Lussenhop, Catherine J; Franck, Carl

    2013-11-01

    Living cells depend upon the detection of chemical signals for their existence. Eukaryotic cells can sense a concentration difference as low as a few per cent across their bodies. This process was previously suggested to be limited by the receptor-ligand binding fluctuations. Here, we first determine the chemotaxis response of Dictyostelium cells to static folic acid gradients and show that they can significantly exceed this sensitivity, responding to gradients as shallow as 0.2% across the cell body. Second, using a previously developed information theory framework, we compare the total information gained about the gradient (based on the cell response) to its upper limit: the information gained at the receptor-ligand binding step. We find that the model originally applied to cAMP sensing fails as demonstrated by the violation of the data processing inequality, i.e. the total information exceeds the information at the receptor-ligand binding step. We propose an extended model with multiple known receptor types and with cells allowed to perform several independent measurements of receptor occupancy. This does not violate the data processing inequality and implies the receptor-ligand binding noise dominates both for low- and high-chemoattractant concentrations. We also speculate that the interplay between exploration and exploitation is used as a strategy for accurate sensing of otherwise unmeasurable levels of a chemoattractant. PMID:24026470

  10. Binding of Folic Acid Induces Specific Self-Aggregation of Lactoferrin: Thermodynamic Characterization.

    PubMed

    Tavares, Guilherme M; Croguennec, Thomas; L, Sbastien; Lerideau, Olivia; Hamon, Pascaline; Carvalho, Antnio F; Bouhallab, Sad

    2015-11-17

    In the study presented here, we investigated the interaction at pH 5.5 between folic acid (FA) and lactoferrin (LF), a positively charged protein. We found a binding constant Ka of 10(5) M(-1) and a high stoichiometry of 10 mol of FA/mol of LF. The size and charge of the complexes formed evolved during titration experiments. Increasing the ionic strength to 50 mM completely abolished the isothermal titration calorimetry (ITC) signal, suggesting the predominance of electrostatic interactions in the exothermic binding obtained. We developed a theoretical model that explains the complex triphasic ITC profile. Our results revealed a two-step mechanism: FA/LF interaction followed by self-association of the complexes thus formed. We suggest that 10 FA molecules bind to LF to form saturated reactive complexes (FA10/LF) that further self-associate into aggregates with a finite size of around 15 nm. There is thus a critical saturation degree of the protein, above which the self-association can take place. We present here the first results that provide comprehensive details of the thermodynamics of FA/LF complexation-association. Given the high stoichiometry, allowing a load of 55 mg of FA/g of LF, we suggest that FA/LF aggregates would be an effective vehicle for FA in fortified drinks. PMID:26488446

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

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

    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).

  12. Folic acid supplementation at lower doses increases oxidative stress resistance and longevity in Caenorhabditis elegans.

    PubMed

    Rathor, Laxmi; Akhoon, Bashir Akhlaq; Pandey, Swapnil; Srivastava, Swati; Pandey, Rakesh

    2015-12-01

    Folic acid (FA) is an essential nutrient that the human body needs but cannot be synthesized on its own. Fortified foods and plant food sources such as green leafy vegetables, beans, fruits, and juices are good sources of FA to meet the daily requirements of the body. The aim was to evaluate the effect of dietary FA levels on the longevity of well-known experimental aging model Caenorhabditis elegans. Here, we show for first time that FA extends organism life span and causes a delay in aging. We observed that FA inhibits mechanistic target of rapamycin (mTOR) and insulin/insulin growth factor 1 (IGF-1) signaling pathways to control both oxidative stress levels and life span. The expression levels of stress- and life span-relevant gerontogenes, viz. daf-16, skn-1, and sir. 2.1, and oxidative enzymes, such as glutathione S-transferase 4 (GST-4) and superoxide dismutase 3 (SOD-3), were also found to be highly enhanced to attenuate the intracellular reactive oxygen species (ROS) damage and to delay the aging process. Our study promotes the use of FA to mitigate abiotic stresses and other aging-related ailments. PMID:26546011

  13. Pharmacodynamics of long-acting folic acid-receptor targeted ritonavir boosted atazanavir nanoformulations

    PubMed Central

    Puligujja, Pavan; Balkundi, Shantanu; Kendrick, Lindsey; Baldridge, Hannah; Hilaire, James; Bade, Aditya N.; Dash, Prasanta K.; Zhang, Gang; Poluektova, Larisa; Gorantla, Santhi; Liu, Xin-Ming; Ying, Tianlei; Feng, Yang; Wang, Yanping; Dimitrov, Dimiter S.; McMillan, JoEllyn M.; Gendelman, Howard E.

    2014-01-01

    Long-acting nanoformulated antiretroviral therapy (nanoART) that target monocyte-macrophage could improve the drug’s half-life and protein binding capacities while facilitating cell and tissue depots. To this end, ART nanoparticles that target the folic acid (FA) receptor and permit cell-based drug depots were examined using pharmacokinetic and pharmacodynamic (PD) tests. FA receptor-targeted poloxamer 407 nanocrystals, containing ritonavir-boosted atazanavir (ATV/r), significantly affected several therapeutic factors: drug bioavailability increased as much as 5 times and PD activity improved as much as 100 times. Drug particles administered to human peripheral blood lymphocyte reconstituted NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ mice and infected with HIV-1ADA at a tissue culture infective dose50 of 104 infectious viral particles/ml led to ATV/r drug concentrations that paralleled FA receptor beta staining in both the macrophage-rich parafollicular areas of spleen and lymph nodes. Drug levels were higher in these tissues than what could be achieved by either native drug or untargeted nanoART particles. The data also mirrored potent reductions in viral loads, tissue viral RNA and numbers of HIV-1p24+ cells in infected and treated animals. We conclude that FA-P407 coating of ART nanoparticles readily facilitate drug carriage and facilitate antiretroviral responses. PMID:25522973

  14. PEGylated polyethylenimine-entrapped gold nanoparticles modified with folic acid for targeted tumor CT imaging.

    PubMed

    Zhou, Benqing; Yang, Jia; Peng, Chen; Zhu, Jianzhi; Tang, Yueqin; Zhu, Xiaoyue; Shen, Mingwu; Zhang, Guixiang; Shi, Xiangyang

    2016-04-01

    Development of various cost-effective contrast agents for targeted tumor computed tomography (CT) imaging still remains a great challenge. Herein, we present a facile approach to forming folic acid (FA)-targeted multifunctional gold nanoparticles (AuNPs) using cost-effective branched polyethylenimine (PEI) modified with polyethylene glycol (PEG) as a template for tumor CT imaging applications. In this work, PEI sequentially modified with PEG monomethyl ether, FA-linked PEG, and fluorescein isothiocyanate was used as a template to synthesize AuNPs, followed by transformation of the remaining PEI surface amines to acetamides. The formed FA-targeted PEI-entrapped AuNPs (FA-Au PENPs) were fully characterized. We show that the formed FA-Au PENPs with an Au core size of 2.1nm are water soluble, colloidally stable, and non-cytotoxic in a given concentration range. Flow cytometry and confocal microscopy data reveal that the FA-Au PENPs are able to target cancer cells overexpressing FA receptors (FAR). Importantly, the developed FA-Au PENPs can be used as a nanoprobe for targeted CT imaging of FAR-expressing cancer cells in vitro and the xenografted tumor model in vivo. With the demonstrated biocompatibility by organ biodistribution and histological studies, the designed FA-Au PENPs may hold great promise to be used as a nanoprobe for CT imaging of different FAR-overexpressing tumors. PMID:26812636

  15. Dual nutraceutical nanohybrids of folic acid and calcium containing layered double hydroxides

    NASA Astrophysics Data System (ADS)

    Kim, Tae-Hyun; Oh, Jae-Min

    2016-01-01

    Dual nutraceutical nanohybrids consisting of organic nutrient, folic acid (FA), and mineral nutrient, calcium, were prepared based on layered double hydroxide (LDH) structure. Among various hybridization methods such as coprecipitation, ion exchange, solid phase reaction and exfoliation-reassembly, it was found that exfoliation-reassembly was the most effective in terms of intercalation of FA moiety between Ca-containing LDH layers. X-ray diffraction patterns and infrared spectra indicated that FA molecules were well stabilized in the interlayer space of LDHs through electrostatic interaction. From the atomic force and scanning electron microscopic studies, particle thickness of LDH was determined to be varied with tens, a few and again tens of nanometers in pristine, exfoliated and reassembled state, respectively, while preserving particle diameter. The result confirmed layer-by-layer hybrid structure of FA and LDHs was obtained by exfoliation-reassembly. Solid UV-vis spectra showed 2-dimensional molecular arrangement of FA moiety in hybrid, exhibiting slight red shift in n→π* and π→π* transition. The chemical formulae of FA intercalated Ca-containing LDH were determined to Ca1.30Al(OH)4.6FA0.74·3.33H2O and Ca1.53Fe(OH)5.06FA2.24·9.94H2O by inductively coupled plasma-atomic emission spectroscopy, high performance liquid chromatography and thermogravimetry, showing high nutraceutical content of FA and Ca.

  16. Encapsulation of folic acid in different silica porous supports: A comparative study.

    PubMed

    Pérez-Esteve, Édgar; Ruiz-Rico, María; de la Torre, Cristina; Villaescusa, Luis A; Sancenón, Felix; Marcos, María D; Amorós, Pedro; Martínez-Máñez, Ramón; Barat, José Manuel

    2016-04-01

    Although folic acid is essential to numerous bodily functions, recent research indicates that a massive exposition to the vitamin could be a double-edged sword. In this study, the capacity of different caped mesoporous silica particles (i.e. Hollow Silica Shells, MCM-41, SBA-15 and UVM-7) to dose FA during its passage through the gastrointestinal tract has been evaluated. Results confirmed that the four capped materials were capable to hinder the delivery of FA at low pH (i.e. stomach) as well as able to deliver great amounts of the vitamin at neutral pH (i.e. intestine). Nevertheless, the encapsulation efficiency and the deliver kinetics differed among supports. While supports with large pore entrance exhibited an initial fast release, MCM-41, showed a sustained release along the time. This correlation between textural properties and release kinetics for each of the supports reveals the importance of a proper support selection as a strategy to control the delivery of active molecules. PMID:26593466

  17. A high sensitive electrochemical nanosensor for simultaneous determination of glutathione, NADH and folic acid.

    PubMed

    Raoof, Jahan Bakhsh; Teymoori, Nader; Khalilzadeh, Mohammad A; Ojani, Reza

    2015-02-01

    In the present study, we report electrosynthesis of 4,5-bis(4-chloroanilino)-1,2-benzendiol (BCB) and its application as a selective electrochemical mediator at a surface of carbon paste electrode (CPE) modified ZnO/CNTs nanocomposite as a simple and rapid voltammetric sensor. The sensor showed an efficient catalytic activity for the electro-oxidation of glutathione (GSH), which leads to a lowered overpotential by more than 203 mV compared to unmodified carbon paste electrode. For the mixture containing GSH, nicotinamide adenine dinucleotide (NADH) and folic acid (FA), the electrooxidation signals were well separated. The square wave voltammetry (SWV) currents increased linearly with their concentration at the ranges of 0.006-161, 1.0-650 and 3.0-700 μM, respectively with the detection limits of 0.002, 0.3 and 1.0 μM. Finally, the electrode was successfully applied for the voltammetric determination of analytes in real samples with satisfactory results. PMID:25492175

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

    PubMed Central

    Joseph, Jacob; Loscalzo, Joseph

    2013-01-01

    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

  19. Voluntary fortification with folic acid in Spain: An updated food composition database.

    PubMed

    Samaniego-Vaesken, M L; Alonso-Aperte, E; Varela-Moreiras, G

    2016-02-15

    Folic acid (FA) is a key vitamin in the prevention of many diseases including neural tube defects. In Spain, only voluntary FA food fortification is allowed and there is a lack of compositional data to assess the contribution of these products to population's dietary folate intakes. Since 2007, our group has been compiling and updating a FA fortified food composition database. FA levels were obtained from retailers in Madrid and information provided by manufacturers. FA was also quantified by an affinity chromatography-HPLC method. In the present study we recorded 375 products. Our results show a high variability in the declared FA levels amongst different products, and food groups, which is also dependant on the commercial brand. FA overages are commonly added by manufacturers to some fortified products. FA content label claims are missing in 64% of products. This database is a useful tool to manage FA fortified foods data but it is necessary to continuously update it for the sound evaluation and monitoring of population's FA dietary intakes. PMID:26433301

  20. Characterization of excipient and tableting factors that influence folic acid dissolution, friability, and breaking strength of oil- and water-soluble multivitamin with minerals tablets.

    PubMed

    Du, Jianping; Hoag, Stephen W

    2003-11-01

    The goal of this study is to characterize the formulation and processing factors that influence folic acid dissolution from oil- and water-soluble multivitamin with minerals tablet formulations for direct compression. The following parameters were studied: bulk filler solubility, soluble to insoluble bulk filler ratio, triturating agent (preblending carrier) solubility, disintegrant usage, compression pressure, and folic acid particle size. Folic acid particle size was determined by using light microscopy, and surface area was measured by using BET adsorption. The tablets were compressed on an instrumented Stokes B2 tablet press, and the friability, weight variation, and dissolution were measured according to USP methods, along with tablet breaking strength. In summary, we found the following factors to be critical to folic acid dissolution: bulk filler solubility (soluble fillers, such as maltose, increase folic acid dissolution); disintegrant amount (levels less than 0.4% (w/w) are ineffectual, whereas levels greater than 1.2% (w/w) did not further increase dissolution); and compression force (generally, maltose produce harder tablets). In addition, folic acid dissolution was less affected by changes in compaction pressure when a "super" disintegrant and maltose, as a bulk filler, were used. It was determined that the trituration agent did not play a significant role in folic acid dissolution. In the range of parameters studied, statistical analysis found no significant interactions between the parameters studied, which means they act independently in an additive manner. The results also show that no one factor is completely responsible for dissolution failure. Thus, it is the combination of formulation factors and processing conditions that collectively add up to produce dissolution failure; however, the use of a disintegrant and a soluble filler such as maltose can make a formulation more robust to the inevitable changes that can occur during commercial production. PMID:14677774

  1. Multifunctional nanosheets based on folic acid modified manganese oxide for tumor-targeting theranostic application

    NASA Astrophysics Data System (ADS)

    Hao, Yongwei; Wang, Lei; Zhang, Bingxiang; Zhao, Hongjuan; Niu, Mengya; Hu, Yujie; Zheng, Cuixia; Zhang, Hongling; Chang, Junbiao; Zhang, Zhenzhong; Zhang, Yun

    2016-01-01

    It is highly desirable to develop smart nanocarriers with stimuli-responsive drug-releasing and diagnostic-imaging functions for cancer theranostics. Herein, we develop a reduction and pH dual-responsive tumor theranostic platform based on degradable manganese dioxide (MnO2) nanosheets. The MnO2 nanosheets with a size of 20-60 nm were first synthesized and modified with (3-Aminopropyl) trimethoxysilane (APTMS) to get amine-functionalized MnO2, and then functionalized by NH2-PEG2000-COOH (PEG). The tumor-targeting group, folic acid (FA), was finally conjugated with the PEGylated MnO2 nanosheets. Then, doxorubicin (DOX), a chemotherapeutic agent, was loaded onto the modified nanosheets through a physical adsorption, which was designated as MnO2-PEG-FA/DOX. The prepared MnO2-PEG-FA/DOX nanosheets with good biocompatibility can not only efficiently deliver DOX to tumor cells in vitro and in vivo, leading to enhanced anti-tumor efficiency, but can also respond to a slightly acidic environment and high concentration of reduced glutathione (GSH), which caused degradation of MnO2 into manganese ions enabling magnetic resonance imaging (MRI). The longitudinal relaxation rate r 1 was 2.26 mM-1 s-1 at pH 5.0 containing 2 mM GSH. These reduction and pH dual-responsive biodegradable nanosheets combining efficient MRI and chemotherapy provide a novel and promising platform for tumor-targeting theranostic application.

  2. Low and high dietary folic acid levels perturb postnatal cerebellar morphology in growing rats.

    PubMed

    Partearroyo, Teresa; Pérez-Miguelsanz, Juliana; Peña-Melián, Ángel; Maestro-de-Las-Casas, Carmen; Úbeda, Natalia; Varela-Moreiras, Gregorio

    2016-06-01

    The brain is particularly sensitive to folate metabolic disturbances, because methyl groups are critical for brain functions. This study aimed to investigate the effects of different dietary levels of folic acid (FA) on postnatal cerebellar morphology, including the architecture and organisation of the various layers. A total of forty male OFA rats (a Sprague-Dawley strain), 5 weeks old, were classified into the following four dietary groups: FA deficient (0 mg/kg FA); FA supplemented (8 mg/kg FA); FA supra-supplemented (40 mg/kg FA); and control (2 mg/kg FA) (all n 10 per group). Rats were fed ad libitum for 30 d. The cerebellum was quickly removed and processed for histological and immunohistochemical analysis. Slides were immunostained for glial fibrillary acidic protein (to label Bergmann glia), calbindin (to label Purkinje cells) and NeuN (to label post-mitotic neurons). Microscopic analysis revealed two types of defect: partial disappearance of fissures and/or neuronal ectopia, primarily in supra-supplemented animals (incidence of 80 %, P≤0·01), but also in deficient and supplemented groups (incidence of 40 %, P≤0·05), compared with control animals. The primary fissure was predominantly affected, sometimes accompanied by defects in the secondary fissure. Our findings show that growing rats fed an FA-modified diet, including both deficient and supplemented diets, have an increased risk of disturbances in cerebellar corticogenesis. Defects caused by these diets may have functional consequences in later life. The present study is the first to demonstrate that cerebellar morphological defects can arise from deficient, as well as high, FA levels in the diet. PMID:27153204

  3. Graphene decorated microelectrodes for simultaneous detection of ascorbic, dopamine, and folic acids by means of chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Namdar, N.; Hassanpour Amiri, M.; Dehghan Nayeri, F.; Gholizadeh, A.; Mohajerzadeh, S.

    2015-09-01

    In this paper, high quality and large area graphene layers were synthesized using thermal chemical vapour deposition on copper foil substrates. We use graphene incorporated electrodes to measure simultaneously ascorbic acid, dopamine and folic acid. Cyclic voltammetry and differential pulse voltammetry methods were used to evaluate electrochemical behaviour of the grown graphene layers. The graphene-modified electrode shows large electrochemical potential difference compared to bare gold electrodes with higher current responses. Also our fabricated electrodes configuration can be used easily for microfluidic analysis.

  4. Folic acid reverses uric acid crystal-induced surface OAT1 internalization by inhibiting RhoA activity in uric acid nephropathy.

    PubMed

    Wu, Xinlin; Liu, Jianxiang; Zhang, Jianqing; Liu, Heng; Yan, Miansheng; Liang, Birong; Xie, Hongbo; Zhang, Shijun; Sun, Baoguo; Zhou, Houming

    2016-03-01

    To investigate how organic anion transporter (OAT)-1 is involved in uric acid nephropathy (UAN), a rat model for UAN was established and the serum uric acid, blood urea nitrogen and serum creatinine levels were all measured, and observed to be increased. It was additionally identified that in UAN rats the surface OAT1 expression levels were reduced. By treating HEK cells with monosodium urate (MSU) crystals, it was observed that the cells exhibited a reduction in OAT1 levels. Furthermore, MSU crystals were observed to recruit Ras homolog family member A (RhoA), a small guanosine triphosphatase, to the membrane and activate it. Following RhoA activation, the OAT1 internalization rate was identified to be increased. The dominant‑negative RhoA N19 mutation was able to block MSU‑induced OAT1 internalization, indicating that the process was RhoA‑dependent. Finally, the results indicated that folic acid, a daily nutritional supplement, was capable of rescuing MSU‑induced nephropathy and OAT1 internalization. These observations indicated that uric acid crystals were able to reduce the OAT1 membrane distribution through activating RhoA, and that folic acid was capable of preventing MSU-induced OAT1 relocation by inhibiting the RhoA signaling pathway. PMID:26846716

  5. Folic acid reverses uric acid crystal-induced surface OAT1 internalization by inhibiting RhoA activity in uric acid nephropathy

    PubMed Central

    WU, XINLIN; LIU, JIANXIANG; ZHANG, JIANQING; LIU, HENG; YAN, MIANSHENG; LIANG, BIRONG; XIE, HONGBO; ZHANG, SHIJUN; SUN, BAOGUO; ZHOU, HOUMING

    2016-01-01

    To investigate how organic anion transporter (OAT)-1 is involved in uric acid nephropathy (UAN), a rat model for UAN was established and the serum uric acid, blood urea nitrogen and serum creatinine levels were all measured, and observed to be increased. It was additionally identified that in UAN rats the surface OAT1 expression levels were reduced. By treating HEK cells with monosodium urate (MSU) crystals, it was observed that the cells exhibited a reduction in OAT1 levels. Furthermore, MSU crystals were observed to recruit Ras homolog family member A (RhoA), a small guanosine triphosphatase, to the membrane and activate it. Following RhoA activation, the OAT1 internalization rate was identified to be increased. The dominant-negative RhoA N19 mutation was able to block MSU-induced OAT1 internalization, indicating that the process was RhoA-dependent. Finally, the results indicated that folic acid, a daily nutritional supplement, was capable of rescuing MSU-induced nephropathy and OAT1 internalization. These observations indicated that uric acid crystals were able to reduce the OAT1 membrane distribution through activating RhoA, and that folic acid was capable of preventing MSU-induced OAT1 relocation by inhibiting the RhoA signaling pathway. PMID:26846716

  6. Effect of in ovo feeding of folic acid on the folate metabolism, immune function and epigenetic modification of immune effector molecules of broiler.

    PubMed

    Li, Shizhao; Zhi, Lihui; Liu, Yanli; Shen, Jing; Liu, Lei; Yao, Junhu; Yang, Xiaojun

    2016-02-14

    This study was conducted to investigate the effect of in ovo feeding (IOF) of folic acid on the folate metabolism, immune function and the involved epigenetic modification of broilers. A total of 400 (Cobb) hatching eggs were randomly divided into four groups (0, 50, 100 and 150 µg injection of folic acid at embryonic age 11 d), and chicks hatched from each treatment were randomly divided into six replicates with 12 broilers/replicate after incubation. The results indicated that, in ovo, 100- and 150-µg folic acid injections improved the hatchability. The average daily gain and feed conversion ratio increased in the 150-µg group during the late growth stage. Simultaneously, in the 100- and 150-µg groups, an increase was observed in hepatic folate content and the expression of methylenetetrahydrofolate reductase (d1 and 42) and methionine synthase reductase (d21). IgG and IgM concentrations, as well as plasma lysozyme activity of broilers, showed a marked increase along with increasing folic acid levels. The splenic expression levels of IL-2 and IL-4 were up-regulated, whereas that of IL-6 was down-regulated, in the 100- and 150-µg folic acid treatment groups. In addition, histone methylation in IL-2 and IL-4 promoters exhibited an enrichment of H3K4m2 but a loss of H3K9me2 with the increased amount of folic acid additive. In contrast, a decrease in H3K4m2 and an increase in H3K9me2 were observed in the IL-6 promoter in folic acid treatments. Furthermore, in ovo, the 150-µg folic acid injection improved the chromatin tightness of the IL-2 and IL-4 promoter regions. Our findings suggest that IOF of 150 µg of folic acid can improve the growth performance and folate metabolism of broilers, and enhance the relationship between immune function and epigenetic regulation of immune genes, which are involved with the alterations in chromatin conformation and histone methylation in their promoters. PMID:26586196

  7. The influence of folic acid depletion on the Nucleotide Excision Repair capacity of human dermal fibroblasts measured by a modified Host Cell Reactivation Assay.

    PubMed

    Burger, Katharina; Kieser, Nicole; Gallinat, S; Mielke, H; Knott, S; Bergemann, Jörg

    2007-01-01

    Animal and human studies have shown that low levels of folic acid are associated with an impaired DNA Repair Capacity (DRC) and an increased cancer risk. However, the molecular evidence that folic acid enhances the DRC of cultured human cells is still limited because of a paucity of in vitro studies. We investigated the effect of folic acid depletion in vitro on the DRC of human dermal fibroblasts derived from 17 donors of different ages. To assess the cellular Nucleotide Excision DRC, we used a modified Host Cell-Reactivation Assay (HCRA), adapted to the Fluorescence Activated Cell Sorting (FACS)-technology, which is highly sensitive in comparison to luminometer-technology and allows single cell based analysis. We used DsRed as a reporter (irradiated with UVC light) and pEGFP to control the performance of the transformations. Folic acid had a statistically significant effect on the DRC in all of the 17 donors, however, the levels varied considerably between individuals (2.0-19.6%). When the effect of folic acid substituted on the DRC was compared to donor age, we observed that there was less DNA repair in old donors compared to the younger donors, although this was only significant at lower levels. PMID:18997281

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

    PubMed

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

    2013-04-01

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

  9. Effects of prenatal and/or postnatal (maternal and/or child) folic acid supplementation on the mental performance of children.

    PubMed

    Skórka, Agata; Gieruszczak-Białek, Dorota; Pieścik, Małgorzata; Szajewska, Hania

    2012-01-01

    It has been suggested that a deficiency in folic acid during early, critical central nervous system development may result in persistent cognitive and behavioral effects. The purpose of this systematic review was to evaluate evidence regarding whether folic acid supplementation during pregnancy and early life influences mental performance outcomes in children. The following electronic databases were searched through December 2009 for studies relevant to mental performance and folic acid: MEDLINE, EMBASE and The Cochrane Library; additional references were obtained from reviewed articles. Only randomized controlled trials (RCTs) were included. Of 8 RCTs identified, only 2 met the inclusion criteria. Both studies involved periconceptional, multivitamin-containing, folic acid supplementation. Evidence from these 2 RCTs suggests that such supplementation does not affect the postnatal mental development of infants at a mean age of 11 mo, the developmental quotient (DQ) at 2 y of age, or the intelligence quotient (IQ) and Goodenough man drawing test quotient (DrQ) at 6 y of age. We conclude that the use of multivitamin-containing folic acid supplementation during pregnancy is associated with no benefit to the mental performance of children. These findings should be interpreted with caution due to the very limited number of studies included in this systemic review. PMID:22823344

  10. Folic Acid and Creatine as Therapeutic Approaches to Lower Blood Arsenic: A Randomized Controlled Trial

    PubMed Central

    Peters, Brandilyn A.; Hall, Megan N.; Liu, Xinhua; Parvez, Faruque; Sanchez, Tiffany R.; van Geen, Alexander; Mey, Jacob L.; Siddique, Abu B.; Shahriar, Hasan; Uddin, Mohammad Nasir; Islam, Tariqul; Balac, Olgica; Ilievski, Vesna; Factor-Litvak, Pam; Graziano, Joseph H.

    2015-01-01

    Background The World Health Organization estimates that > 140 million people worldwide are exposed to arsenic (As)–contaminated drinking water. As undergoes biologic methylation, which facilitates renal As elimination. In folate-deficient individuals, this process is augmented by folic acid (FA) supplementation, thereby lowering blood As (bAs). Creatinine concentrations in urine are a robust predictor of As methylation patterns. Although the reasons for this are unclear, creatine synthesis is a major consumer of methyl donors, and this synthesis is down-regulated by dietary/supplemental creatine. Objectives Our aim was to determine whether 400 or 800 μg FA and/or creatine supplementation lowers bAs in an As-exposed Bangladeshi population. Methods We conducted a clinical trial in which 622 participants were randomized to receive 400 μg FA, 800 μg FA, 3 g creatine, 3 g creatine+400 μg FA, or placebo daily. All participants received an As-removal filter on enrollment, and were followed for 24 weeks. After the 12th week, half of the two FA groups were switched to placebo to evaluate post-treatment bAs patterns. Results Linear models with repeated measures indicated that the decline in ln(bAs) from baseline in the 800-μg FA group exceeded that of the placebo group (weeks 1–12: β= –0.09, 95% CI: –0.18, –0.01; weeks 13–24: FA continued: β= –0.12, 95% CI: –0.24, –0.00; FA switched to placebo: β= –0.14, 95% CI: –0.26, –0.02). There was no rebound in bAs related to cessation of FA supplementation. Declines in bAs observed in the remaining treatment arms were not significantly different from those of the placebo group. Conclusions In this mixed folate-deficient/replete study population, 12- and 24-week treatment with 800 μg (but not 400 μg) FA lowered bAs to a greater extent than placebo; this was sustained 12 weeks after FA cessation. In future studies, we will evaluate whether FA and/or creatine altered As methylation profiles. Citation Peters BA, Hall MN, Liu X, Parvez F, Sanchez TR, van Geen A, Mey JL, Siddique AB, Shahriar H, Uddin MN, Islam T, Balac O, Ilievski V, Factor-Litvak P, Graziano JH, Gamble MV. 2015. Folic acid and creatine as therapeutic approaches to lower blood arsenic: a randomized controlled trial. Environ Health Perspect 123:1294–1301; http://dx.doi.org/10.1289/ehp.1409396 PMID:25978852

  11. Determinants of folic acid intake during preconception and in early pregnancy by mothers in Ibadan, Nigeria

    PubMed Central

    Lawal, Taiwo Akeem; Adeleye, Amos Olufemi

    2014-01-01

    Introduction In order to identify targets for primary preventive strategies, we explored possible predictors of periconceptional folic acid (pFA) intake in a Nigerian population of reproductively active women. Methods A cross sectional study of mothers attending immunization clinics at two hospitals was conducted between May and November 2012. Information obtained included sociodemographic and obstetric details and periconceptional usage of FA. Independent variables were analysed as predictors of pFA intake using chi-square statistical test and multinomial logistic regression. Results The study involved 602 mothers aged 17 to 42 years; 23% had a university degree and 66% were in the working class. Preconceptional usage was proven in only 15 (2.5%). Periconceptional usage was more likely among professionals (X2 = 41.194, p < 0.001), have university degree (X2 = 53.089, p < 0.001), be primigravid (X2 = 18.415, p < 0.001) and early antenatal clinic attendees (X2 = 355.9, p < 0.001). Women were less likely to know that FA could prevent birth defects if in the working class (1.7% vs. 11.1%, X2 = 25.593, p < 0.001), less educated (0.5 vs. 10.9%, X2 = 38.083, p < 0.001) or booked late for antenatal care (2.0 vs. 5.9%, X2 = 5.767, p = 0.016). The determinants of late commencement of FA were low social class (OR = 4.29, 95% CI: 1.59, 11.31), lack of university education (OR = 4.58, 95% CI: 3.06, 6.87) and late booking (OR = 104.27, 95% CI: 53.09, 204.76). Conclusion In this population of reproductively active women, pFA intake and knowledge of its health benefits are poor amongst mothers - in working class, with limited education, and who present late for antenatal care. PMID:25722786

  12. When folic acid fails: Insights from 20 years of neural tube defect surveillance in South Carolina.

    PubMed

    Bupp, Caleb P; Sarasua, Sara M; Dean, Jane H; Stevenson, Roger E

    2015-10-01

    Neural tube defects (NTDs) are the most common of the severe malformations of the brain and spinal cord. Increased maternal intake of folic acid (FA) during the periconceptional period is known to reduce NTD risk. Data from 1046 NTD cases in South Carolina were gathered over 20 years of surveillance. It was possible to determine maternal periconceptional FA use in 615 NTD-affected pregnancies. In 163 occurrent (26.9%) and two recurrent (22%) NTD cases, the mothers reported periconceptional FA use. These women were older and more likely to be white. Maternal periconceptional FA usage was reported in 40.4% of cases of spina bifida with other anomalies but in only 25.2% of isolated spina bifida cases (P = 0.02). This enrichment for associated anomalies was not noted among cases of anencephaly or of encephalocele. Among the 563 subsequent pregnancies to mothers with previous NTD-affected pregnancies, those taking FA had a 0.4% NTD recurrence rate, but the recurrence without FA was 8.5%. NTDs with other associated findings were less likely to be prevented by FA, suggesting there is a background NTD rate that cannot be further reduced by FA. Nonetheless, the majority (73.9%) of NTDs in pregnancies in which the mothers reported periconceptional FA use were isolated NTDs of usual types. Cases in which FA failed in prevention of NTDs provide potential areas for further study into the causation of NTDs. The measures and techniques implemented in South Carolina can serve as an effective and successful model for prevention of NTD occurrence and recurrence. PMID:26108864

  13. Photoinduced Electron Transfer in Folic Acid Investigated by Ultrafast Infrared Spectroscopy

    PubMed Central

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

    2012-01-01

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

  14. Folic Acid Linked Chondroitin Sulfate-Polyethyleneimine Copolymer Based Gene Delivery System.

    PubMed

    Lo, Yu-Lun; Lo, Pei-Chi; Chiu, Chien-Chih; Wang, Li-Fang

    2015-08-01

    In our previous study, chondroitin sulfate-polyethylenimine copolymers (CP) have been synthesized and confirmed as potential gene delivery vectors. Efficient gene transfection is realized by chondroitin sulfate (ChS) that promotes CD44- mediated endocytosis and enhances the cellular uptake of CP/pDNA polyplexes besides clathrin-mediated endocytosis. In this study, the CP was functionalized with a folic acid (FA) molecule. This ancillary ligand allows polyplexes to bind with folate receptors (FR) in addition to the CD44 receptor. We conjugated FA-linked polyethylene glycol (FA-PEG) onto CP (FPCP) for tumor targeting and also synthesized mPEG-CP (MPCP) for comparison. The in vitro cell tests of polymer/pDNA polyplexes were done in FR-expressed U87 and FR-deficient A549 cells. The polymers exhibited less cytotoxicity than PEI-10K as well as PEI-25K against U87 and A549 cells. The transfection efficiency of FPCP/pDNA was higher than those of MPCP/pDNA and CP/pDNA. The cellular uptake pathways of FPCP/pDNA were tested in the cells in the presence of different endocytic chemical inhibitors. The CD44-, folate-, and caveolae-mediated pathways are involved in internalization of FPCP/pDNA. Recognition of FPCP to those receptors on the tumor surface is beneficial for enhanced cellular uptake of FPCP/pDNA, resulting in higher transgene expression than CP/pDNA and MPCP/pDNA. PMID:26295140

  15. Antiinflammatory Activity of a Novel Folic Acid Targeted Conjugate of the mTOR Inhibitor Everolimus

    PubMed Central

    Lu, Yingjuan; Parker, Nikki; Kleindl, Paul J; Cross, Vicky A; Wollak, Kristin; Westrick, Elaine; Stinnette, Torian W; Gehrke, Mark A; Wang, Kevin; Santhapuram, Hari Krishna R; You, Fei; Hahn, Spencer J; Vaughn, Jeremy F; Klein, Patrick J; Vlahov, Iontcho R; Low, Philip S; Leamon, Christopher P

    2015-01-01

    Folate receptor (FR)-? has been identified as a promising target for antimacrophage and antiinflammatory therapies. In the present study, we investigated EC0565, a folic acidderivative of everolimus, as a FR-specific inhibitor of the mammalian target of rapamycin (mTOR). Because of its amphiphilic nature, EC0565 was first evaluated for water solubility, critical micelle formation, stability in culture and FR-binding specificity. Using FR-expressing macrophages, the effect of EC0565 on mTOR signaling and cellular proliferation was studied. The pharmacokinetics, metabolism and bioavailability of EC0565 were studied in normal rats. The in vivo activity of EC0565 was assessed in rats with adjuvant arthritis, a macrophage-rich model with close resemblance to rheumatoid arthritis. EC0565 forms micellar aggregates in physiological buffers and demonstrates good water solubility as well as strong multivalent FR-binding capacity. EC0565 inhibited mTOR signaling in rat macrophages at nanomolar concentrations and induced G0/G1 cell cycle arrest in serum-starved RAW264.7 cells. Subcutaneously administered EC0565 in rats displayed good bioavailability and a relatively long half-life (~12 h). When given at 250 nmol/kg, EC0565 selectively inhibited proliferating cell nuclear antigen expression in thioglycollate-stimulated rat peritoneal cells. With limited dosing regimens, the antiarthritic activity of EC0565 was found superior to that of etanercept, everolimus and a nontargeted everolimus analog. The in vivo activity of EC0565 was also comparable to that of a folate-targeted aminopterin. Folate-targeted mTOR inhibition may be an effective way of suppressing activated macrophages in sites of inflammation, especially in nutrient-deprived conditions, such as in the arthritic joints. Further investigation and improvement upon the physical and biochemical properties of EC0565 are warranted. PMID:26181632

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

    PubMed

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

    2015-07-14

    The majority of neural tube defects were believed to be folic acid (FA)-preventable in the 1990s. The Japanese government recommended women planning pregnancy to take FA supplements of 400 μg/d in 2000, but the incidence of spina bifida has not decreased. We aimed to evaluate the OR of having an infant with spina bifida for women who periconceptionally took FA supplements and the association between an increase in supplement use and possible promoters for the increase. This is a case-control study which used 360 case women who gave birth to newborns afflicted with spina bifida, and 2333 control women who gave birth to healthy newborns during the first 12 years of this century. They were divided into two 6-year periods; from 2001 to 2006 and from 2007 to 2012. Logistic regression analyses were conducted to compute OR between cases and controls. The adjusted OR of having an infant with spina bifida for supplement users was 0.48 in the first period, and 0.53 in the second period. The proportion of women who periconceptionally consumed supplements significantly increased from 10 % in the first period to 30 % in the second period. Awareness of the preventive role of FA was a promoter for an increase in supplement use, and thus an FA campaign in high school seems rational and effective. The failure of the current public health policy is responsible for an epidemic of spina bifida. Mandatory food fortification with FA is urgent and long overdue in Japan. PMID:25999131

  17. Carbobenzoxy amino acids: Structural requirements for cholecystokinin receptor antagonist activity

    SciTech Connect

    Maton, P.N.; Sutliff, V.E.; Jensen, R.T.; Gardner, J.D.

    1985-04-01

    The authors used dispersed acini prepared from guinea pig pancreas to examine 28 carbobenzoxy (CBZ) amino acids for their abilities to function as cholecystokinin receptor antagonists. All amino acid derivatives tested, except for CBZ-alanine, CBZ-glycine, and N alpha-CBZ- lysine, were able to inhibit the stimulation of amylase secretion caused by the C-terminal octapeptide of cholecystokinin. In general, there was a good correlation between the ability of a carbobenzoxy amino acid to inhibit stimulated amylase secretion and the ability of the amino acid derivative to inhibit binding of /sup 125/I-cholecystokinin. The inhibition of cholecystokinin-stimulated amylase secretion was competitive, fully reversible, and specific for those secretagogues that interact with the cholecystokinin receptor. The potencies with which the various carbobenzoxy amino acids inhibited the action of cholecystokinin varied 100-fold and CBZ-cystine was the most potent cholecystokinin receptor antagonist. This variation in potency was primarily but not exclusively a function of the hydrophobicity of the amino acid side chain.

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

    PubMed Central

    2014-01-01

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

  19. Multifunctional biocompatible and biodegradable folic acid conjugated poly(ε-caprolactone)-polypeptide copolymer vesicles with excellent antibacterial activities.

    PubMed

    Wang, Mingzhi; Zhou, Chuncai; Chen, Jing; Xiao, Yufen; Du, Jianzhong

    2015-04-15

    Cancer patients after chemotherapy may also suffer bacterial attack due to badly decreased immunity. Although with high bacterial efficacy, conventional antibiotics are prone to inducement of drug resistance and may be not suitable for some cancer patients. In contrast, antibacterial peptides are highly effective in inhibiting bacteria without inducing resistance in pathogens. Presented in this article is a novel kind of highly effective antibacterial peptide-based biocompatible and biodegradable block copolymer vesicle. The copolymer is poly(ε-caprolactone)-block-poly[phenylalanine-stat-lysine-stat-(lysine-folic acid)] [PCL19-b-poly[Phe12-stat-Lys9-stat-(Lys-FA)6

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

    PubMed

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

    2014-01-01

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

  1. Teratogenic effects of diabetic conditions in chick heart in ovo and in micromass culture may be prevented by addition of vitamin C and folic acid.

    PubMed

    Memon, Samreen; Pratten, Margaret K

    2013-01-01

    Maternal diseases like diabetes mellitus may cause developmental defects. Supplementation with folic acid and vitamin C during the periconceptional period has been shown to prevent some neural tube and congenital heart defects. Hearts were dissected from 5 days-old White Leghorn chick embryos, the cells isolated and cultured in micromass under diabetic conditions, with and without folic acid and vitamin C. Contractile activity, cell viability (resazurin reduction) and protein assays were performed. Results indicated diabetic conditions reduced contractile activity and cell viability, whilst vitamin C (100 μM) and folic acid (1 mM) administered concurrently significantly improved them to values comparable with the control. Day 3 chick embryos in ovo were injected with glucose+hydroxybutyrate or a combination of these and vitamins. Diabetic conditions caused gross and histological malformations, but these effects were abrogated by vitamin supplement. Teratogenic effects on heart development could possibly be prevented by vitamin supplementation during pregnancy. PMID:23099339

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

    PubMed

    Bhoite, Rachana M; Iyer, Uma M

    2012-08-01

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

  3. Folic acid-Pluronic F127 magnetic nanoparticle clusters for combined targeting, diagnosis, and therapy applications.

    PubMed

    Lin, Jia-Jyun; Chen, Jenn-Shing; Huang, Shih-Jer; Ko, Jyun-Han; Wang, Yu-Ming; Chen, Ting-Lung; Wang, Li-Fang

    2009-10-01

    Superparamagnetic iron oxides possess specific magnetic properties in the presence of an external magnetic field, which make them an attractive platform as contrast agents for magnetic resonance imaging (MRI) and as carriers for drug delivery. In this study, we investigate the drug delivery and the MRI properties of folate-mediated water-soluble iron oxide incorporated into micelles. Pluronic F127 (PF127), which can be self-assembled into micelles upon increasing concentration or raising temperatures, is used to decorate water-soluble polyacrylic acid-bound iron oxides (PAAIO) via a chemical reaction. Next, the hydrophobic dye Nile red is encapsulated into the hydrophobic poly(propylene oxide) compartment of PF127 as a model drug and as a fluorescent agent. Upon encapsulation, PAAIO retains its superparamagnetic characteristics, and thus can be used for MR imaging. A tumor-specific targeting ligand, folic acid (FA), is conjugated onto PF127-PAAIO to produce a multifunctional superparamagnetic iron oxide, FA-PF127-PAAIO. FA-PF127-PAAIO can be simultaneously applied as a diagnostic and therapeutic agent that specifically targets cancer cells that overexpress folate receptors in their cell membranes. PF127-PAAIO is used as a reference group. Based on FTIR and UV-vis absorbance spectra, the successful synthesis of PF127-PAAIO and FA-PF127-PAAIO is realized. The magnetic nanoparticle clusters of PF127-PAAIO and FA-PF127-PAAIO are visualized by transmission electron microscope (TEM). FA-PF127-PAAIO, together with a targeting ligand, displays a higher intracellular uptake into KB cells. This result is confirmed by laser confocal scanning microscopy (CLSM), flow cytometry, and atomic absorption spectroscopy (AAS) studies. The hysteresis curves, generated by using a superconducting quantum interference device (SQUID) magnetometer analysis, demonstrate that the magnetic nanoparticles are superparamagnetic with insignificant hysteresis. The MTT assay explains the negligible cell cytotoxicity of PF127-PAAIO and FA-PF127-PAAIO. In KB cells, the in vitro MRI study indicates the better T(2)-weighted images in FA-PF127-PAAIO than in PF127-PAAIO. PMID:19560199

  4. [Differences in folic-acid policy and the prevalence of neural-tube defects in Europe; recommendations for food fortification in a EUROCAT report].

    PubMed

    Meijer, W M; de Walle, H E K

    2005-11-12

    The European Registration Of Congenital Anomalies and Twins (EUROCAT), a network of 40 European registries of congenital anomalies, has published a special report on the prevention of neural-tube defects by, periconceptional folic-acid supplementation in Europe. This report reviews the progress made in 17 European countries since i99I in terms of developing and implementing public health policies to raise periconceptional folate status. Data on the prevalence of neural-tube defects in 1980-2000 were also analysed. - At the beginning of 2002, 10 of the 17 countries had an official government recommendation that women planning a pregnancy should take folic-acid supplementation daily. Only 7 countries implemented official health-education initiatives. - Despite the various measures taken to date, the majority of women in all countries surveyed are not taking periconceptional folic-acid supplements. Even in the Netherlands, where the percentage of planned pregnancies is estimated at 85%, only 36% of women take folic-acid supplements during the advised period. - Overall, the number of neural-tube defects has not decreased in Europe. A slight decrease was seen in those countries with an official policy regarding periconceptional folic-acid supplementation. - It is clear from the report that more effective prevention of neuraltube defects could be achieved with folic-acid fortification of staple foods; this approach has led to a reduction in the prevalence of neuraltube defects in the US and Canada. This approach can also prevent the majority of neural-tube defects in unplanned pregnancies and reduce the socioeconomic differences in prevalence. PMID:16320666

  5. Folic Acid Represses Hypoxia-Induced Inflammation in THP-1 Cells through Inhibition of the PI3K/Akt/HIF-1α Pathway

    PubMed Central

    Jiang, Xinwei; Hou, Mengjun; Tang, Zhihong; Zhen, Xiaozhou; Liang, Yuming; Ma, Jing

    2016-01-01

    Though hypoxia has been implicated as a cause of inflammation, the underlying mechanism is not well understood. Folic acid has been shown to provide protection against oxidative stress and inflammation in patients with cardiovascular disease and various models approximating insult to tissue via inflammation. It has been reported that hypoxia-induced inflammation is associated with oxidative stress, upregulation of hypoxia-inducible factor 1-alpha (HIF-1α), and production of pro-inflammatory molecules. Whether folic acid protects human monocytic cells (THP-1 cells) against hypoxia-induced damage, however, remains unknown. We used THP-1 cells to establish a hypoxia-induced cellular injury model. Pretreating THP-1 cells with folic acid attenuated hypoxia-induced inflammatory responses, including a decrease in protein and mRNA levels of interleukin (IL)-1β and tumor necrosis factor-alpha (TNF-α), coupled with increased levels of IL-10. Folic acid also reduced hypoxia-induced Akt phosphorylation and decreased nuclear accumulation of HIF-1α protein. Both LY294002 (a selective inhibitor of phosphatidyl inositol-3 kinase, PI3K) and KC7F2 (a HIF-1α inhibitor) reduced levels of hypoxia-induced inflammatory cytokines. We also found that insulin (an Akt activator) and dimethyloxallyl glycine (DMOG, a HIF-1α activator) induced over-expression of inflammatory cytokines, which could be blocked by folic acid. Taken together, these findings demonstrate how folic acid attenuates the hypoxia-induced inflammatory responses of THP-1 cells through inhibition of the PI3K/Akt/HIF-1α pathway. PMID:26974319

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

    PubMed

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

    2013-09-01

    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

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

    PubMed Central

    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

    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. PMID:21987466

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

    PubMed

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

    2009-04-01

    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

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

    PubMed

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

    2005-02-01

    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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2012-07-23

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

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

    PubMed Central

    Ionescu-Ittu, Raluca; Marelli, Ariane J; Mackie, Andrew S

    2009-01-01

    Objective To investigate whether the 1998 government policy for mandatory fortification of flour and pasta products with folate was followed by a reduction in the prevalence of severe congenital heart defects. Design Time trend analysis. Setting Province of Quebec, Canada. Participants Infants born in 1990-2005 identified with severe congenital heart defects (tetralogy of Fallot, endocardial cushion defects, univentricular hearts, truncus arteriosus, or transposition complexes) in Quebec administrative databases. Methods Data analysed in two time periods (before and after fortification). Birth prevalence measured annually as infants (live and stillbirths) with severe congenital heart defects per 1000 births in Quebec. Changes in the birth prevalence from the period before to the period after fortification were estimated with Poisson regression. Results Among the 1 324 440 births in Quebec in 1990-2005 there were 2083 infants born with severe congenital heart defects, corresponding to an average birth prevalence of 1.57/1000 births. Time trend analysis showed no change in the birth prevalence of severe birth defects in the nine years before fortification (rate ratio 1.01, 95% confidence interval 0.99 to 1.03), while in the seven years after fortification there was a significant 6% decrease per year (0.94, 0.90 to 0.97). Conclusions Public health measures to increase folic acid intake were followed by a decrease in the birth prevalence of severe congenital heart defects. These findings support the hypothesis that folic acid has a preventive effect on heart defects. PMID:19436079

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

    SciTech Connect

    Mason, J.B.; Selhub, J.

    1988-09-01

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

  14. Identification of a Chemoattractant G-Protein-Coupled Receptor for Folic Acid that Controls Both Chemotaxis and Phagocytosis.

    PubMed

    Pan, Miao; Xu, Xuehua; Chen, Yong; Jin, Tian

    2016-02-22

    Eukaryotic phagocytes search and destroy invading microorganisms via chemotaxis and phagocytosis. The social amoeba Dictyostelium discoideum is a professional phagocyte that chases bacteria through chemotaxis and engulfs them as food via phagocytosis. G-protein-coupled receptors (GPCRs) are known for detecting chemoattractants and directing cell migration, but their roles in phagocytosis are not clear. Here, we developed a quantitative phosphoproteomic technique to discover signaling components. Using this approach, we discovered the long sought after folic acid receptor, fAR1, in D. discoideum. We showed that the seven-transmembrane receptor fAR1 is required for folic acid-mediated signaling events. Significantly, we discovered that fAR1 is essential for both chemotaxis and phagocytosis of bacteria, thereby representing a chemoattractant GPCR that mediates not only chasing but also ingesting bacteria. We revealed that a phagocyte is able to internalize particles via a chemoattractant-mediated engulfment process. We propose that mammalian phagocytes may also use this mechanism to engulf and ingest bacterial pathogens. PMID:26906738

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

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

    2014-01-01

    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. PMID:24736781

  17. Effect of niacin and folic acid in feed rations on growth and live weights of Green catfish (Mystus nemurus Valenciennes 1840).

    PubMed

    Hien, D V; Doolgindachbaporn, S

    2011-01-01

    This study aims to justify effects of niacin and folic acid in feed rations on growth and survival rate of the fish under in vitro conditions. A Completely Randomized Design (CRD) with four replications for Experiment I and three replications for Experiment II was used. Niacin (0, 5, 10, 20 and 40 mg kg(-1)) and folic acid (0, 2, 4, 6 and 8 mg kg(-1)) were used for Experiments I, and II, respectively. The cement tanks were used for Experiment I and fibre tanks for Experiment II. A static water system was used. Water temperature was maintained at a range from 26 to 30 degrees C with pH values from 7.4 to 7.9. The results showed that niacin at a rate of 10 mg kg(-1) feed ration gave significant differences on weight gained %, survival %, protein efficiency ratio, specific growth rate % and feed conversion ratio with mean values of 99.92, 100, 1.18, 5.77 and 1.35, respectively. Folic acid at a rate of 2 mg kg(-1) gave significant differences on weight gained %, survival %, protein efficiency ratio, specific growth rate % and feed conversion ratio with mean values of 108.88, 100, 1.22, 6.13 and 1.43, respectively. Niacin at a rate of 10 and 2 mg kg(-1) of folic acid were the best rates for in vitro culture of Green catfish. PMID:21913500

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  20. 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

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

    1993-01-01

    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. PMID:8221478

  1. Effects of intramuscular administration of folic acid and vitamin B12 on granulosa cells gene expression in postpartum dairy cows.

    PubMed

    Gagnon, A; Khan, D R; Sirard, M-A; Girard, C L; Laforest, J-P; Richard, F J

    2015-11-01

    The fertility of dairy cows is challenged during early lactation, and better nutritional strategies need to be developed to address this issue. Combined supplementation of folic acid and vitamin B12 improve energy metabolism in the dairy cow during early lactation. Therefore, the present study was undertaken to explore the effects of this supplement on gene expression in granulosa cells from the dominant follicle during the postpartum period. Multiparous Holstein cows received weekly intramuscular injection of 320 mg of folic acid and 10 mg of vitamin B12 (treated group) beginning 24 (standard deviation=4) d before calving until 56 d after calving, whereas the control group received saline. The urea plasma concentration was significantly decreased during the precalving period, and the concentration of both folate and vitamin B12 were increased in treated animals. Milk production and dry matter intake were not significantly different between the 2 groups. Plasma concentrations of folates and vitamin B12 were increased in treated animals. Daily dry matter intake was not significantly different between the 2 groups before [13.5 kg; standard error (SE)=0.5] and after (23.6 kg; SE=0.9) calving. Average energy-corrected milk tended to be greater in vitamin-treated cows, 39.7 (SE=1.4) and 38.1 (SE=1.3) kg/d for treated and control cows, respectively. After calving, average plasma concentration of β-hydroxybutyrate tended to be lower in cows injected with the vitamin supplement, 0.47 (SE=0.04) versus 0.55 (SE=0.03) for treated and control cows, respectively. The ovarian follicle ≥12 mm in diameter was collected by ovum pick-up after estrus synchronization. Recovered follicular fluid volumes were greater in the vitamin-treated group. A microarray platform was used to investigate the effect of treatment on gene expression of granulosa cells. Lower expression of genes involved in the cell cycle and higher expression of genes associated with granulosa cell differentiation before ovulation were observed. Selected candidate genes were analyzed by reverse transcription quantitative PCR. Although the effects of intramuscular injections of folic acid and vitamin B12 on lactational performance and metabolic status of animals were limited, ingenuity pathway analysis of gene expression in granulosa cells suggests a stimulation of cell differentiation in vitamin-treated cows, which may be the result of an increase in LH secretion. PMID:26298749

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

    PubMed Central

    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

    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. PMID:22163281

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

    PubMed Central

    Morse, Nancy L.

    2012-01-01

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

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

    PubMed

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

    2014-06-01

    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

  5. Implementing preventive iron-folic acid supplementation among women of reproductive age in some Western Pacific countries: possibilities and challenges.

    PubMed

    Smitasiri, Suttilak; Solon, Florentino S

    2005-12-01

    Lack of effective implementation mechanisms is identified as a major obstacle in the prevention and control of iron-deficiency anemia. This paper discusses experiences gained from implementing iron-folic acid supplementation in the Philippines, Vietnam, and Cambodia. The understanding of contextual elements is proposed as a foundation for planning interventions. Moreover, it is suggested that a social marketing framework should provide a way of thinking about how to influence related behaviors. The application of a social marketing framework applied using a "5 P's" approach: public relations and collaboration, product, price, place, and promotion, is described, as well as enabling factors (possibilities) and inhibiting factors (challenges) of this approach. Although a program to improve iron nutrition among women of reproductive age may not be simple to implement, it is essential to enhancing health, human development, and economic advancement in developing countries. PMID:16466083

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

    PubMed

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

    2015-03-01

    The development of probes for biomedical applications demands materials with low toxicity levels besides fluorescence or magnetic properties to be detected by confocal microscopes or MRI resonators. Several drug delivery systems or other biomedical materials prepared with hydroxyapatite have been proposed, however, toxicity effects might arise when the size of particles is nanometric. In this study, hydroxyapatite functionalized with glucuronic or folic acids presented lower oxidative stress, measured from lipoperoxides and nitric oxide indicators in rats than pure hydroxyapatite. In separated experiments, hydroxyapatite was doped with dysprosium cations by coprecipitation producing a single crystal phase with fluorescent properties easily visualized by confocal microscopy when excited at 488nm. These particles also presented the ability to modify the proton relaxation time in T1 maps collected by magnetic resonance imaging. These modified hydroxyapatite nanoparticles could be candidates to design bimodal probes with low toxicity. PMID:25579955

  7. Photodynamic therapy effect of zinc monoamino phthalocyanine-folic acid conjugate adsorbed on single walled carbon nanotubes on melanoma cells

    NASA Astrophysics Data System (ADS)

    Ogbodu, Racheal O.; Ndhundhuma, Ivy; Karsten, Aletta; Nyokong, Tebello

    2015-02-01

    This work reports on the photodynamic therapy effect of zinc monoamino phthalocyanine linked to folic acid represented as ZnMAPc-FA, which was further immobilized onto single walled carbon nanotube represented as ZnMAPc-FA-SWCNT on melanoma A375 cell line, the effect of SWCNT-FA (without ZnMAPc) was also examined. All the compounds were non-toxic to the melanoma A375 cell line in the absence of light. Upon irradiation of the melanoma A375 cell line with a 676 nm diode laser at a power density of 98 mW/cm2 at 5 J/cm2 about 60% and 63% cell death was observed in the presence of ZnMAPc-FA and ZnMAPc-FA-SWCNT respectively. SWCNT-FA had no significant photodynamic therapy or photothermal effect to the cell, only 23% of cell death was observed after irradiation.

  8. Neural Tube Defects in Costa Rica, 1987–2012: Origins and Development of Birth Defect Surveillance and Folic Acid Fortification

    PubMed Central

    de la Paz Barboza-Argüello, María; Umaña-Solís, Lila M.; Azofeifa, Alejandro; Valencia, Diana; Flores, Alina L.; Rodríguez-Aguilar, Sara; Alfaro-Calvo, Thelma; Mulinare, Joseph

    2015-01-01

    Our aim was to provide a descriptive overview of how the birth defects surveillance and folic acid fortification programs were implemented in Costa Rica—through the establishment of the Registry Center for Congenital Anomalies (Centro de Registro de Enfermedades Congénitas—CREC), and fortification legislation mandates. We estimated the overall prevalence of neural tube defects (i.e., spina bifida, anencephaly and encephalocele) before and after fortification captured by CREC. Prevalence was calculated by dividing the total number of infants born with neural tube defects by the total number of live births in the country (1987–2012).A total of 1,170 newborns with neural tube defects were identified from 1987 to 2012 (1992–1995 data excluded); 628 were identified during the baseline pre-fortification period (1987–1991; 1996–1998); 191 during the fortification period (1999–2002); and 351 during the post-fortification time period (2003–2012). The overall prevalence of neural tube defects decreased from 9.8 per 10,000 live-births (95 % CI 9.1–10.5) for the pre-fortification period to 4.8 per 10,000 live births (95 % CI 4.3–5.3) for the post–fortification period. Results indicate a statistically significant (P < 0.05) decrease of 51 % in the prevalence of neural tube defects from the pre-fortification period to the post-fortification period. Folic acid fortification via several basic food sources has shown to be a successful public health intervention for Costa Rica. Costa Rica’s experience can serve as an example for other countries seeking to develop and strengthen both their birth defects surveillance and fortification programs. PMID:24952876

  9. Folic Acid Supplementation Ameliorates Oxidative Stress, Metabolic Functions and Developmental Anomalies in a Novel Fly Model of Parkinson's Disease.

    PubMed

    Srivastav, Saurabh; Singh, Sandeep Kumar; Yadav, Amarish Kumar; Srikrishna, Saripella

    2015-07-01

    Mutations in parkin cause early-onset Parkinson's disease. Studies involving Drosophila model have emphasised mitochondrial dysfunction as a critical event in disease pathogenesis. In this context, we employed a novel recessive allele of parkin, park (c00062) , for the current study. The piggyBac insertion at 3rd intron of parkin in park (c00062) was confirmed by PCR. Homozygous park (c00062) has diminished levels of truncated parkin transcript with no detectable protein as confirmed by qRT-PCR and western blot analysis, respectively. The homozygous park (c00062) displayed severe developmental anomalies involving reduced body size, ~45 % pupal lethality, high mortality with locomotory defect, elevated oxidative stress, low metabolic active cell status with low mitochondrial respiration as reflected from reduced ATP levels. Further, folic acid therapeutic potential was analysed in park (c00062) . Here we show that dietary folic acid provided protection against disparities involving pupal lethality, high mortality, locomotory defect, elevated oxidative stress and low metabolic active cell status associated with park (c00062) . Further mitochondrial respiration was enhanced as reflected from improved ATP levels in folate supplemented park (c00062) . To corroborate mitochondrial functioning further our analysis regarding transcript status of p53 and spargel by qRT-PCR, revealed down regulation of p53 and up regulation of spargel in folate supplemented park (c00062) , which was originally vice a versa. Our data thus support the potential of FA in alleviating the disparities associated with parkin loss of function in fly model. Further, FA role in alleviating mitochondrial dysfunction is encouraging to further explore FA mechanistic role to be utilized as potential therapeutics for parkin mediated neurodegenerative diseases. PMID:25963948

  10. Folic acid supplementation in pregnancy to prevent preterm birth: a systematic review and meta-analysis of randomized controlled trials.

    PubMed

    Saccone, Gabriele; Berghella, Vincenzo

    2016-04-01

    Folic acid (FA) may have a role in the prevention of pregnancy complications. However, the efficacy of FA supplementation in reducing the risk of preterm birth (PTB) is still unclear. The aim of this systematic review with meta-analysis was to evaluate the efficacy of folic acid supplementation during pregnancy to prevent preterm birth (PTB). The research protocol was designed a priori, defining methods for searching the literature in electronic databases, including and examining articles, and extracting and analyzing data. We included all randomized trials (RCTs) of asymptomatic singleton gestations without prior PTB who were randomized to prophylactic treatment with either FA supplementation or control (placebo or no treatment). The primary outcome was the incidence of PTB <37 weeks. Five randomized trials including 5,332 asymptomatic singleton gestations without prior PTB were included in the analysis. Women who received FA supplementation had a similar rate of PTB <37 weeks (22.6% vs 22.9%; RR 0.99, 95% CI 0.82-1.18), PTB<34 weeks (7.1% vs 8.7%; RR 0.77, 95% CI 0.55-1.09) and of preterm premature rupture of membranes (2.4% vs 2.9%; RR 0.81, 95% CI 0.44-1.50) compared with control group. Regarding neonatal outcome we found no significant differences in birth weight (mean difference 85.58g, 95% CI -55.17-226.34), low birth weight (21.0% vs 15.1%; RR 0.79, 95% CI 0.49 to 1.28) and perinatal death (2.9% vs 2.4%; RR 0.90, 95% CI 0.60-1.34). In summary, FA supplementation during pregnancy does not prevent PTB <37 weeks. Daily FA supplementation remains the most important intervention to reduce the risk of neural tube defects. PMID:26901401

  11. Neural tube defects in Costa Rica, 1987-2012: origins and development of birth defect surveillance and folic acid fortification.

    PubMed

    Barboza-Argüello, María de la Paz; Umaña-Solís, Lila M; Azofeifa, Alejandro; Valencia, Diana; Flores, Alina L; Rodríguez-Aguilar, Sara; Alfaro-Calvo, Thelma; Mulinare, Joseph

    2015-03-01

    Our aim was to provide a descriptive overview of how the birth defects surveillance and folic acid fortification programs were implemented in Costa Rica-through the establishment of the Registry Center for Congenital Anomalies (Centro de Registro de Enfermedades Congénitas-CREC), and fortification legislation mandates. We estimated the overall prevalence of neural tube defects (i.e., spina bifida, anencephaly and encephalocele) before and after fortification captured by CREC. Prevalence was calculated by dividing the total number of infants born with neural tube defects by the total number of live births in the country (1987-2012).A total of 1,170 newborns with neural tube defects were identified from 1987 to 2012 (1992-1995 data excluded); 628 were identified during the baseline pre-fortification period (1987-1991; 1996-1998); 191 during the fortification period (1999-2002); and 351 during the post-fortification time period (2003-2012). The overall prevalence of neural tube defects decreased from 9.8 per 10,000 live-births (95 % CI 9.1-10.5) for the pre-fortification period to 4.8 per 10,000 live births (95 % CI 4.3-5.3) for the post-fortification period. Results indicate a statistically significant (P < 0.05) decrease of 51 % in the prevalence of neural tube defects from the pre-fortification period to the post-fortification period. Folic acid fortification via several basic food sources has shown to be a successful public health intervention for Costa Rica. Costa Rica's experience can serve as an example for other countries seeking to develop and strengthen both their birth defects surveillance and fortification programs. PMID:24952876

  12. The restrained expression of NF-kB in renal tissue ameliorates folic acid induced acute kidney injury in mice.

    PubMed

    Kumar, Dev; Singla, Surinder K; Puri, Veena; Puri, Sanjeev

    2015-01-01

    The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) represent family of structurally-related eukaryotic transcription factors which regulate diverse array of cellular processes including immunological responses, inflammation, apoptosis, growth & development. Increased expression of NF-kB has often been seen in many diverse diseases, suggesting the importance of genomic deregulation to disease pathophysiology. In the present study we focused on acute kidney injury (AKI), which remains one of the major risk factor showing a high rate of mortality and morbidity. The pathology associated with it, however, remains incompletely known though inflammation has been reported to be one of the major risk factor in the disease pathophysiology. The role of NF-kB thus seemed pertinent. In the present study we show that high dose of folic acid (FA) induced acute kidney injury (AKI) characterized by elevation in levels of blood urea nitrogen & serum creatinine together with extensive tubular necrosis, loss of brush border and marked reduction in mitochondria. One of the salient observations of this study was a coupled increase in the expression of renal, relA, NF-kB2, and p53 genes and proteins during folic acid induced AKI (FA AKI). Treatment of mice with NF-kB inhibitor, pyrrolidine dithio-carbamate ammonium (PDTC) lowered the expression of these transcription factors and ameliorated the aberrant renal function by decreasing serum creatinine levels. In conclusion, our results suggested that NF-kB plays a pivotal role in maintaining renal function that also involved regulating p53 levels during FA AKI. PMID:25559736

  13. The Restrained Expression of NF-kB in Renal Tissue Ameliorates Folic Acid Induced Acute Kidney Injury in Mice

    PubMed Central

    Kumar, Dev; Singla, Surinder K.; Puri, Veena; Puri, Sanjeev

    2015-01-01

    The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) represent family of structurally-related eukaryotic transcription factors which regulate diverse array of cellular processes including immunological responses, inflammation, apoptosis, growth & development. Increased expression of NF-kB has often been seen in many diverse diseases, suggesting the importance of genomic deregulation to disease pathophysiology. In the present study we focused on acute kidney injury (AKI), which remains one of the major risk factor showing a high rate of mortality and morbidity. The pathology associated with it, however, remains incompletely known though inflammation has been reported to be one of the major risk factor in the disease pathophysiology. The role of NF-kB thus seemed pertinent. In the present study we show that high dose of folic acid (FA) induced acute kidney injury (AKI) characterized by elevation in levels of blood urea nitrogen & serum creatinine together with extensive tubular necrosis, loss of brush border and marked reduction in mitochondria. One of the salient observations of this study was a coupled increase in the expression of renal, relA, NF-kB2, and p53 genes and proteins during folic acid induced AKI (FA AKI). Treatment of mice with NF-kB inhibitor, pyrrolidine dithio-carbamate ammonium (PDTC) lowered the expression of these transcription factors and ameliorated the aberrant renal function by decreasing serum creatinine levels. In conclusion, our results suggested that NF-kB plays a pivotal role in maintaining renal function that also involved regulating p53 levels during FA AKI. PMID:25559736

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

    PubMed Central

    2013-01-01

    Background Gastric cancer is 2th most common cancer in China, and is still the second most common cause of cancer-related death in the world. Successful development of safe and effective nanoprobes for in vivo gastric cancer targeting imaging is a big challenge. This study is aimed to develop folic acid (FA)-conjugated silica coated gold nanoclusters (AuNCs) for targeted dual-modal fluorescent and X-ray computed tomography imaging (CT) of in vivo gastric cancer cells. Method AuNCs were prepared, silica was coated on the surface of AuNCs, then folic acid was covalently anchored on the surface of AuNCs, resultant FA-conjugated AuNCs@SiO2 nanoprobes were investigated their cytotoxicity by MTT method, and their targeted ability to FR(+) MGC803 cells and FR(−) GES-1 cells. Nude mice model loaded with MGC803 cells were prepared, prepared nanoprobes were injected into nude mice via tail vein, and then were imaged by fluorescent and X-ray computed tomography (CT) imaging. Results FA-conjugated AuNCs@SiO2 nanoprobes exhibited good biocompatibility, and could target actively the FR(+) MGC-803 cells and in vivo gastric cancer tissues with 5 mm in diameter in nude mice models, exhibited excellent red emitting fluorescence imaging and CT imaging. Conclusion The high-performance FA-conjugated AuNCs@SiO2 nanoprobes can target in vivo gastric cancer cells, can be used for fluorescent and CT dual-mode imaging, and may own great potential in applications such as targeted dual-mode imaging of in vivo early gastric cancer and other tumors with FR positive expression in near future. PMID:23718865

  15. Crystal Structure of Antagonist Bound Human Lysophosphatidic Acid Receptor 1.

    PubMed

    Chrencik, Jill E; Roth, Christopher B; Terakado, Masahiko; Kurata, Haruto; Omi, Rie; Kihara, Yasuyuki; Warshaviak, Dora; Nakade, Shinji; Asmar-Rovira, Guillermo; Mileni, Mauro; Mizuno, Hirotaka; Griffith, Mark T; Rodgers, Caroline; Han, Gye Won; Velasquez, Jeffrey; Chun, Jerold; Stevens, Raymond C; Hanson, Michael A

    2015-06-18

    Lipid biology continues to emerge as an area of significant therapeutic interest, particularly as the result of an enhanced understanding of the wealth of signaling molecules with diverse physiological properties. This growth in knowledge is epitomized by lysophosphatidic acid (LPA), which functions through interactions with at least six cognate G protein-coupled receptors. Herein, we present three crystal structures of LPA1 in complex with antagonist tool compounds selected and designed through structural and stability analyses. Structural analysis combined with molecular dynamics identified a basis for ligand access to the LPA1 binding pocket from the extracellular space contrasting with the proposed access for the sphingosine 1-phosphate receptor. Characteristics of the LPA1 binding pocket raise the possibility of promiscuous ligand recognition of phosphorylated endocannabinoids. Cell-based assays confirmed this hypothesis, linking the distinct receptor systems through metabolically related ligands with potential functional and therapeutic implications for treatment of disease. PMID:26091040

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

    PubMed

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

    2012-01-27

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

  17. 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

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

    2012-01-01

    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. PMID:22848174

  18. Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy.

    PubMed

    Bwatanglang, Ibrahim Birma; Mohammad, Faruq; Yusof, Nor Azah; Abdullah, Jaafar; Hussein, Mohd Zobir; Alitheen, Noorjahan Banu; Abu, Nadiah

    2016-01-01

    In this study, we synthesized a multifunctional nanoparticulate system with specific targeting, imaging, and drug delivering functionalities by following a three-step protocol that operates at room temperature and solely in aqueous media. The synthesis involves the encapsulation of luminescent Mn:ZnS quantum dots (QDs) with chitosan not only as a stabilizer in biological environment, but also to further provide active binding sites for the conjugation of other biomolecules. Folic acid was incorporated as targeting agent for the specific targeting of the nanocarrier toward the cells overexpressing folate receptors. Thus, the formed composite emits orange-red fluorescence around 600 nm and investigated to the highest intensity at Mn(2+) doping concentration of 15 at.% and relatively more stable at low acidic and low alkaline pH levels. The structural characteristics and optical properties were thoroughly analyzed by using Fourier transform infrared, X-ray diffraction, dynamic light scattering, ultraviolet-visible, and fluorescence spectroscopy. Further characterization was conducted using thermogravimetric analysis, high-resolution transmission electron microscopy, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray fluorescence, and X-ray photoelectron spectroscopy. The cell viability and proliferation studies by means of MTT assay have demonstrated that the as-synthesized composites do not exhibit any toxicity toward the human breast cell line MCF-10 (noncancer) and the breast cancer cell lines (MCF-7 and MDA-MB-231) up to a 500 µg/mL concentration. The cellular uptake of the nanocomposites was assayed by confocal laser scanning microscope by taking advantage of the conjugated Mn:ZnS QDs as fluorescence makers. The result showed that the functionalization of the chitosan-encapsulated QDs with folic acid enhanced the internalization and binding affinity of the nanocarrier toward folate receptor-overexpressed cells. Therefore, we hypothesized that due to the nontoxic nature of the composite, the as-synthesized nanoparticulate system can be used as a promising candidate for theranostic applications, especially for a simultaneous targeted drug delivery and cellular imaging. PMID:26858524

  19. Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy

    PubMed Central

    Bwatanglang, Ibrahim Birma; Mohammad, Faruq; Yusof, Nor Azah; Abdullah, Jaafar; Hussein, Mohd Zobir; Alitheen, Noorjahan Banu; Abu, Nadiah

    2016-01-01

    In this study, we synthesized a multifunctional nanoparticulate system with specific targeting, imaging, and drug delivering functionalities by following a three-step protocol that operates at room temperature and solely in aqueous media. The synthesis involves the encapsulation of luminescent Mn:ZnS quantum dots (QDs) with chitosan not only as a stabilizer in biological environment, but also to further provide active binding sites for the conjugation of other biomolecules. Folic acid was incorporated as targeting agent for the specific targeting of the nanocarrier toward the cells overexpressing folate receptors. Thus, the formed composite emits orange–red fluorescence around 600 nm and investigated to the highest intensity at Mn2+ doping concentration of 15 at.% and relatively more stable at low acidic and low alkaline pH levels. The structural characteristics and optical properties were thoroughly analyzed by using Fourier transform infrared, X-ray diffraction, dynamic light scattering, ultraviolet-visible, and fluorescence spectroscopy. Further characterization was conducted using thermogravimetric analysis, high-resolution transmission electron microscopy, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray fluorescence, and X-ray photoelectron spectroscopy. The cell viability and proliferation studies by means of MTT assay have demonstrated that the as-synthesized composites do not exhibit any toxicity toward the human breast cell line MCF-10 (noncancer) and the breast cancer cell lines (MCF-7 and MDA-MB-231) up to a 500 µg/mL concentration. The cellular uptake of the nanocomposites was assayed by confocal laser scanning microscope by taking advantage of the conjugated Mn:ZnS QDs as fluorescence makers. The result showed that the functionalization of the chitosan-encapsulated QDs with folic acid enhanced the internalization and binding affinity of the nanocarrier toward folate receptor-overexpressed cells. Therefore, we hypothesized that due to the nontoxic nature of the composite, the as-synthesized nanoparticulate system can be used as a promising candidate for theranostic applications, especially for a simultaneous targeted drug delivery and cellular imaging. PMID:26858524

  20. Effect of prenatal exposure to ethanol on hepatic elongation factor-2 and proteome in 21 d old rats: protective effect of folic acid.

    PubMed

    García-Rodríguez, S; Argüelles, S; Llopis, R; Murillo, M L; Machado, A; Carreras, O; Ayala, A

    2003-08-15

    In this article, we study the effects of ethanol intake during pregnancy and lactation on hepatic and pancreatic elongation factor-2 (EF-2) of 21 d old progeny. At the same time, the effect of ethanol on the level of other relevant hepatic proteins was determined using proteomic analysis. The results show that ethanol not only produces a general increase of protein oxidation, but also produces an important depletion of EF-2 and several other proteins. Among the hepatic proteins affected by ethanol, the concomitant supplementation with folic acid to alcoholic mother rats prevented EF-2, RhoGDI-1, ER-60 protease, and gelsolin depletion. This protective effect of folic acid may be related to its antioxidant properties and suggests that this vitamin may be useful in minimizing the effect of ethanol in the uterus and lactation exposure of the progeny. PMID:12899944

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

    PubMed Central

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

    2011-01-01

    In this study, folic-dextran-camptothecin (Fa-DEX-CPT) tumor-targeted nanoparticles were produced with a supercritical antisolvent (SAS) technique by using dimethyl sulfoxide (DMSO) as a solvent and carbon dioxide as an antisolvent. A factorial design was used to reveal the effect of various process parameters on the mean particle size (MPS) and morphology of the particles formed. Under the optimum operation conditions, Fa-DEX-CPT nanoparticles with a MPS of 182.21 nm were obtained. Drug encapsulation efficiency and loading efficiency were 62.13% and 36.12%, respectively. It was found that the concentrations of the camptothecin (CPT) and dextran solution had a major influence upon morphology and shape of the final product. In addition, the samples were characterized by Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) with the purpose of developing a suitable targeted drug delivery system for cancer chemotherapy. PMID:21845075

  2. Folic acid supplementation rescues anomalies associated with knockdown of parkin in dopaminergic and serotonergic neurons inDrosophila model of Parkinson's disease.

    PubMed

    Srivastav, Saurabh; Singh, Sandeep Kumar; Yadav, Amarish Kumar; Srikrishna, Saripella

    2015-05-01

    parkin loss associated early-onset of Parkinson's disease, involves mitochondrial dysfunction and oxidative stress as the plausible decisive molecular mechanisms in disease pathogenesis. Mitochondrial dysfunction involves several up/down regulation of gene products, one of which being p53 is found to be elevated. Elevated p53 is involved in mitochondrial mediated apoptosis of neuronal cells in Parkinson's patients who are folate deficient as well. The present study therefore attempts to examine the effect of Folic acid (FA) supplementation in alleviation of anomalies associated with parkin knockdown using RNAi approach, specific to Dopaminergic (DA) neurons in Drosophila model system. Here we show that FA supplementation provide protection against parkin RNAi associated discrepancies, thereby improves locomotor ability, reduces mortality and oxidative stress, and partially improves Zn levels. Further, metabolic active cell status and ATP levels were also found to be improved thereby indicating improved mitochondrial function. To corroborate FA supplementation in mitochondrial functioning further, status of p53 and spargel was checked by qRT-PCR. Here we show that folic acid supplementation enrich mitochondrial functioning as depicted from improved spargel level and lowered p53 level, which was originally vice versa in parkin knockdown flies cultured in standard media. Our data thus support the potential of folic acid in alleviating the behavioural defects, oxidative stress, augmentation of zinc and ATP levels in parkin knock down flies. Further, folic acid role in repressing mitochondrial dysfunction is encouraging to further explore its possible mechanistic role to be utilized as potential therapeutics for Parkinson's disease. PMID:25824034

  3. Methyltetrahydrofolate vs Folic Acid Supplementation in Idiopathic Recurrent Miscarriage with Respect to Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms: A Randomized Controlled Trial

    PubMed Central

    Hekmatdoost, Azita; Vahid, Farhad; Yari, Zahra; Sadeghi, Mohammadreza; Eini-Zinab, Hassan; Lakpour, Niknam; Arefi, Soheila

    2015-01-01

    Purpose To determine whether 5-methylenetetrahydrofolate (MTHF) is more effective than folic acid supplementation in treatment of recurrent abortion in different MTHFR gene C677T and A1298C polymorphisms. Methods A randomized, double blind, placebo-controlled trial conducted April 2011-September 2014 in recurrent abortion clinics in Tehran, Iran. The participants were women with three or more idiopathic recurrent abortion, aged 20 to 45 years. Two hundred and twenty eligible women who consented to participate were randomly assigned to receive either folic acid or 5-MTHF according to the stratified blocked randomization by age and the number of previous abortions. Participants took daily 1 mg 5-methylentetrahydrofolate or 1 mg folic acid from at least 8 weeks before conception to the 20th week of the pregnancy. The primary outcome was ongoing pregnancy rate at 20th week of pregnancy, and the secondary outcomes were serum folate and homocysteine at the baseline, after 8 weeks, and at the gestational age of 4, 8, 12, and 20 weeks, MTHFR gene C677T and A1298C polymorphisms. Results There was no significant difference in abortion rate between two groups. Serum folate increased significantly in both groups over time; these changes were significantly higher in the group receiving 5-MTHF than the group receiving folic acid (value = 2.39, p<00.1) and the result was the same by considering the time (value = 1.24, p<0.01). Plasma tHcys decreased significantly in both groups over time; however these changes were not significantly different between the groups (value = 0.01, p = 0.47). Conclusion The results do not support any beneficial effect of 5-MTHF vs. folate supplementation in women with recurrent abortion with any MTHFR C677T and/or A1298C polymorphism. Trial Registration ClinicalTrials.gov NCT01976676 PMID:26630680

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

    A novel chemiluminescence (CL) method using water-soluble Mn-doped ZnS quantum dots (QDs) as CL emitter is proposed for the chemiluminometric determination of folic acid in pharmaceutical formulation. Water-soluble Mn-doped ZnS QDs were synthesized by using L-cysteine as stabilizer in aqueous solutions. The nanoparticles were structurally and optically characterized by X-ray powder diffraction (XRD), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), UV-Vis absorption spectroscopy and photoluminescence (PL) emission spectroscopy. The CL of ZnS QDs induced by directly chemical oxidation and its ionic liquid-sensitized effect in aqueous solution were then investigated. It was found that oxidants, especially hydrogen peroxide, could directly oxidize ZnS QDs to produce weak CL emission in basic conditions. In the presence of 1,3-dipropylimidazolium bromide/copper a drastic light emission enhancement is observed, related to a strong interaction between Cu2+ and the imidazolium ring. Therefore, a new CL analysis system was developed for the determination of folic acid. Under the optimum conditions, there is a good linear relationship between the relative CL intensity and the concentration of folic acid in the range of 1 × 10-9-1 × 10-6 M of folic acid with a correlation coefficient (R2) of 0.9991. The limit of detection of this system was found to be 1 × 10-10 M. This method is not only simple, sensitive and low cost, but also reliable for practical applications.

  5. Vitamin B12 and Folic Acid Improve Gross Motor and Problem-Solving Skills in Young North Indian Children: A Randomized Placebo-Controlled Trial

    PubMed Central

    Kvestad, Ingrid; Taneja, Sunita; Kumar, Tivendra; Hysing, Mari; Refsum, Helga; Yajnik, Chittaranjan S.; Bhandari, Nita; Strand, Tor A.

    2015-01-01

    Objectives Deficiencies of vitamin B12 and folate are associated with delayed development and neurological manifestations. The objective of this study was to measure the effect of daily supplementation of vitamin B12 and/or folic acid on development in young North Indian children. Methods In a randomized, double blind trial, children aged six to 30 months, received supplement with placebo or vitamin B12 and/or folic acid for six months. Children were allocated in a 1:1:1:1 ratio in a factorial design and in blocks of 16. We measured development in 422 children by the Ages and Stages Questionnaire 3rd ed. at the end of the intervention. Results Compared to placebo, children who received both vitamin B12 and folic acid had 0.45 (95% CI 0.19, 0.73) and 0.28 (95% CI 0.02, 0.54) higher SD-units in the domains of gross motor and problem solving functioning, respectively. The effect was highest in susceptible subgroups consisting of stunted children, those with high plasma homocysteine (> 10 μmol/L) or in those who were younger than 24 at end study. With the exception of a significant improvement on gross motor scores by vitamin B12 alone, supplementation of either vitamin alone had no effect on any of the outcomes. Conclusion Our findings suggest that supplementation of vitamin B12 and folic acid benefit development in North Indian Children. Trial Registration ClinicalTrials.gov NCT00717730 PMID:26098427

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

    PubMed

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

    2014-03-01

    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

  7. Folic acid deficiency increases delayed neuronal death, DNA damage, platelet endothelial cell adhesion molecule-1 immunoreactivity, and gliosis in the hippocampus after transient cerebral ischemia.

    PubMed

    Hwang, In Koo; Yoo, Ki-Yeon; Suh, Hong-Won; Kim, Young Sup; Kwon, Dae Young; Kwon, Young-Guen; Yoo, Jun-Hyun; Won, Moo-Ho

    2008-07-01

    Folic acid deficiency increases stroke risk. In the present study, we examined whether folic acid deficiency enhances neuronal damage and gliosis via oxidative stress in the gerbil hippocampus after transient forebrain ischemia. Animals were exposed to a folic acid-deficient diet (FAD) for 3 months and then subjected to occlusion of both common carotid arteries for 5 min. Exposure to an FAD increased plasma homocysteine levels by five- to eightfold compared with those of animals fed with a control diet (CD). In CD-treated animals, most neurons were dead in the hippocampal CA1 region 4 days after ischemia/reperfusion, whereas, in FAD-treated animals, this occurred 3 days after ischemia/reperfusion. Immunostaining for 8-hydroxy-2'-deoxyguanosine (8-OHdG) was performed to examine DNA damage in CA1 neurons in both groups after ischemia, and it was found that 8-OHdG immunoreactivity in both FAD and CD groups peaked at 12 hr after reperfusion, although the immunoreactivity in the FAD group was much greater than that in the CD group. Platelet endothelial cell adhesion molecule-1 (PECAM-1; a final mediator of neutrophil transendothelial migration) immunoreactivity in both groups increased with time after ischemia/reperfusion: Its immunoreactivity in the FAD group was much higher than that in the CD group 3 days after ischemia/reperfusion. In addition, reactive gliosis in the ischemic CA1 region increased with time after ischemia in both groups, but astrocytosis and microgliosis in the FAD group were more severe than in the CD group at all times after ischemia. Our results suggest that folic acid deficiency enhances neuronal damage induced by ischemia. PMID:18335523

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

    PubMed

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

    2014-03-25

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

  9. Carbon dots on based folic acid coated with PAMAM dendrimer as platform for Pt(IV) detection.

    PubMed

    Campos, Bruno B; Oliva, María Moreno; Contreras-Cáceres, Rafael; Rodriguez-Castellón, Enrique; Jiménez-Jiménez, José; da Silva, Joaquim C G Esteves; Algarra, Manuel

    2016-03-01

    Carbon quantum dots (CQDs) coated with poly(amidoamine) (PAMAM-NH2) dendrimer are prepared from folic acid and phosphoric acid under a hydrothermal procedure. The obtained nanoparticles are successfully used as fluorescent sensor for Pt(IV) (in the form of chloroplatinate ion). CQDs possess many attractive features including uniform dispersion with average size about 13nm for unmodified particles and, ∼30nm when they are coated with PAMAM-NH2 dendrimer. The synthesized nanoparticles have been characterized by elemental analysis, attenuated total reflectance (ATR), X-ray photoelectron (XPS) and Raman spectroscopies, transmission electron microscopy (TEM), dynamic light scattering (DLS), and steady-state and life-time fluorescence. CQDs are used as fluorescent sensor of Pt(IV) ion in aqueous media showing linear quenching effect of their fluorescence. The results obtained demonstrated a limit of detection of 657nM with an accuracy of the method of 0.13% (as RSD, n=10) and sensitivity of 78nM. Moreover, with the presence of other interference species, good results are obtained when applied in real samples from platinum nanoparticles synthesis. The dissolved platinum ions can be quantified in the range 6-96μM with an accuracy of 2.5%. PMID:26674232

  10. Comparative Transcriptome Analysis Reveals the Influence of Abscisic Acid on the Metabolism of Pigments, Ascorbic Acid and Folic Acid during Strawberry Fruit Ripening

    PubMed Central

    Luo, Zisheng; Mou, Wangshu; Mao, Linchun; Ying, Tiejin

    2015-01-01

    A comprehensive investigation of abscisic acid (ABA) biosynthesis and its influence on other important phytochemicals is critical for understanding the versatile roles that ABA plays during strawberry fruit ripening. Using RNA-seq technology, we sampled strawberry fruit in response to ABA or nordihydroguaiaretic acid (NDGA; an ABA biosynthesis blocker) treatment during ripening and assessed the expression changes of genes involved in the metabolism of pigments, ascorbic acid (AsA) and folic acid in the receptacles. The transcriptome analysis identified a lot of genes differentially expressed in response to ABA or NDGA treatment. In particular, genes in the anthocyanin biosynthesis pathway were actively regulated by ABA, with the exception of the gene encoding cinnamate 4-hydroxylase. Chlorophyll degradation was accelerated by ABA mainly owing to the higher expression of gene encoding pheide a oxygenase. The decrease of β-carotene content was accelerated by ABA treatment and delayed by NDGA. A high negative correlation rate was found between ABA and β-carotene content, indicating the importance of the requirement for ABA synthesis during fruit ripening. In addition, evaluation on the folate biosynthetic pathway indicate that ABA might have minor function in this nutrient’s biosynthesis process, however, it might be involved in its homeostasis. Surprisingly, though AsA content accumulated during fruit ripening, expressions of genes involved in its biosynthesis in the receptacles were significantly lower in ABA-treated fruits. This transcriptome analysis expands our understanding of ABA’s role in phytochemical metabolism during strawberry fruit ripening and the regulatory mechanisms of ABA on these pathways were discussed. Our study provides a wealth of genetic information in the metabolism pathways and may be helpful for molecular manipulation in the future. PMID:26053069

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

    NASA Astrophysics Data System (ADS)

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

    2012-09-01

    The salient features of the present work focus on the synthesis of CuO nanoleaves by alcoholic reduction of Cu(II) chloride in the presence of poly(diallyldimethylammonium chloride) (PDDA) for the application of folic acid oxidation in simulated body fluid environment. PDDA-assisted polyol process allows a conventional impregnation method for the formation of CuO with well-defined leaf-like structure. The structure and morphology of the CuO nanoleaves were characterized by Fourier-transform infrared (FT-IR) spectroscopy and X-ray diffraction (XRD) analysis. Field emission scanning electron microscope (FESEM) image confirms the formations of CuO with leaf-like morphology and branched side edges. The average size of the resultant CuO nanoleaves was calculated to be 400 nm in length and 150 nm in width. The electrochemical performance of the CuONs/MWCNTs/GCE nanocomposite modified electrode was characterized by cyclic voltammetric (CV) studies. The CuONs/MWCNTs/GCE nanocomposite modified electrode shows good electrochemical activity and it was also found that it possessed prominent electrocatalytic activity toward the oxidation of folic acid with as high a sensitivity as 3.35 ?A/?M and a low detection limit (3 ?) of 15.2 nM (S/N = 3). Besides, the CuO nanocomposite modified electrode lowers the over potential of folic acid oxidation than the unmodified electrodes.

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

    PubMed Central

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

    2014-01-01

    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. PMID:25035638

  13. 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

    2012-01-01

    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 μmol/L relative to those with < 130 μmol/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. PMID:22233538

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

    PubMed Central

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

    2012-01-01

    Background A critical disadvantage for successful chemotherapy with paclitaxel (PTX) is its nontargeting nature to cancer cells. Folic acid has been employed as a targeting ligand of various anticancer agents to increase their cellular uptake within target cells since the folate receptor is overexpressed on the surface of such tumor cells. In this study, a novel biodegradable deoxycholic acid-O-carboxymethylated chitosan–folic acid conjugate (DOMC-FA) was used to form micelles for encapsulating the anticancer drug PTX. Methods and results The drug-loading efficiency, encapsulation efficiency, in vitro drug release and physicochemical properties of PTX-loaded micelles were investigated in detail. In vitro cell culture studies were carried out in MCF-7 cells, a human breast carcinoma cell line, with folate receptor overexpressed on its surface. An increased level of uptake of folate-conjugated micelles compared to plain micelles in MCF-7 cells was observed, and the enhanced uptake of folate-micelles mainly on account of the effective process of folate receptor-mediated endocytosis. The MTT assay, morphological changes, and apoptosis test implied that the folate-conjugated micelles enhanced the cell death by folate-mediated active internalization, and the cytotoxicity of the FA-micellar PTX (DOMC-FA/PTX) to cancer cells was much higher than micelles without folate (DOMC/PTX) or the commercially available injectable preparation of PTX (Taxol). Conclusion Results indicate that the PTX-loaded DOMC-FA micelle is a successful anticancertargeted drug-delivery system for effective cancer chemotherapy. PMID:22287842

  15. Folic Acid and Vitamins D and B12 Correlate With Homocysteine in Chinese Patients With Type-2 Diabetes Mellitus, Hypertension, or Cardiovascular Disease

    PubMed Central

    Mao, Xudong; Xing, Xubin; Xu, Rong; Gong, Qing; He, Yue; Li, Shuijun; Wang, Hongfu; Liu, Cong; Ding, Xin; Na, Rishu; Liu, Zhiwen; Qu, Yi

    2016-01-01

    Abstract Elevated serum homocysteine has been shown to be a risk factor for hypertension, cardiovascular disease (CVD), and type-2 diabetes mellitus (T2DM). We characterized the relationships between the serum levels of homocysteine, folic acid, and vitamins D2, D3, and B12 in patients with T2DM, CVD, and hypertension in Shanghai, China. The levels of these serum biochemical markers were determined for 9311 Chinese patients (mean age: 79.50 ± 13.26 years) with T2DM (N = 839), hypertension (N = 490), or CVD (N = 7925). The demographic and serum biochemical data were compared using an analysis of variance. We performed stratified analyses using Pearson linear regression to investigate correlations between the different variables in the T2DM, CVD, and hypertension groups and in patients aged < 50, 50 to 64, 65 to 80, and ≥80 years. A subgroup analysis was also performed to identify correlations between the serum biochemical markers. Stratified chi-squared analyses were performed based on the levels of folic acid and total vitamin D. In all 3 patient groups, elevated levels of vitamin D2 and homocysteine were observed, whereas the levels of folic acid and vitamins D3 and B12 were lower than the reference range for each serum marker (P < 0.05 for all). The linear regression and stratified analyses showed that the highest levels of folic acid and vitamins D2 and D3 correlated with the lowest level of homocysteine in T2DM, CVD, and hypertension patients (P < 0.05 for all), whereas the highest level of vitamin B12 correlated with a lowest level of homocysteine in CVD patients only (P < 0.05). Our results indicate that the contributions of both vitamin D2 and vitamin D3 should be considered in investigations of the effects of vitamin D supplements in T2DM, CVD, and hypertension patients. Our findings warrant future studies of the benefits of vitamin D and folic acid supplements for reducing the risk of T2DM, CVD, and hypertension in elderly Chinese people, as well as the benefits of vitamin B12 supplements for reducing the risk of CVD alone. PMID:26871790

  16. Folic acid conjugated cross-linked acrylic polymer (FA-CLAP) hydrogel for site specific delivery of hydrophobic drugs to cancer cells

    PubMed Central

    2014-01-01

    Background The hydrogel based system is found to be rarely reported for the delivery of hydrophobic drug due to the incompatibility of hydrophilicity of the polymer network and the hydrophobicity of drug. This problem can be solved by preparing semi-interpenetrating network of cross-linked polymer for tuning the hydrophilicity so as to entrap the hydrophobic drugs. The current study is to develop a folic acid conjugated cross-linked pH sensitive, biocompatible polymeric hydrogel to achieve a site specific drug delivery. For that, we have synthesized a folic acid conjugated PEG cross-linked acrylic polymer (FA-CLAP) hydrogel and investigated its loading and release of curcumin. The formed polymer hydrogel was then conjugated with folic acid for the site specific delivery of curcumin to cancer cells and then further characterized and conducted the cell uptake and cytotoxicity studies on human cervical cancer cell lines (HeLa). Results In this study, we synthesized folic acid conjugated cross-linked acrylic hydrogel for the delivery of hydrophobic drugs to the cancer site. Poly (ethyleneglycol) (PEG) diacrylate cross-linked acrylic polymer (PAA) was prepared via inverse emulsion polymerization technique and later conjugated it with folic acid (FA-CLAP). Hydrophobic drug curcumin is entrapped into it and investigated the entrapment efficiency. Characterization of synthesized hydogel was done by using Fourier Transform-Infrared spectroscopy (FT-IR), Transmission Electron Microscopy (TEM), Differential Scanning Calorimetry (DSC). Polymerization and folate conjugation was confirmed by FT-IR spectroscopy. The release kinetics of drug from the entrapped form was studied which showed initial burst release followed by sustained release due to swelling and increased cross-linking. In vitro cytotoxicity and cell uptake studies were conducted in human cervical cancer (HeLa) cell lines. Conclusions Results showed that curcumin entrapped folate conjugated cross-linked acrylic polymer (FA-CLAP) hydrogel showed higher cellular uptake than the non folate conjugated form. So this can be suggested as a better delivery system for site specific release of hydrophobic cancer drugs. PMID:25026938

  17. Folic Acid and Vitamins D and B12 Correlate With Homocysteine in Chinese Patients With Type-2 Diabetes Mellitus, Hypertension, or Cardiovascular Disease.

    PubMed

    Mao, Xudong; Xing, Xubin; Xu, Rong; Gong, Qing; He, Yue; Li, Shuijun; Wang, Hongfu; Liu, Cong; Ding, Xin; Na, Rishu; Liu, Zhiwen; Qu, Yi

    2016-02-01

    Elevated serum homocysteine has been shown to be a risk factor for hypertension, cardiovascular disease (CVD), and type-2 diabetes mellitus (T2DM).We characterized the relationships between the serum levels of homocysteine, folic acid, and vitamins D2, D3, and B12 in patients with T2DM, CVD, and hypertension in Shanghai, China. The levels of these serum biochemical markers were determined for 9311 Chinese patients (mean age: 79.50??13.26 years) with T2DM (N?=?839), hypertension (N?=?490), or CVD (N?=?7925). The demographic and serum biochemical data were compared using an analysis of variance. We performed stratified analyses using Pearson linear regression to investigate correlations between the different variables in the T2DM, CVD, and hypertension groups and in patients aged?folic acid and total vitamin D.In all 3 patient groups, elevated levels of vitamin D2 and homocysteine were observed, whereas the levels of folic acid and vitamins D3 and B12 were lower than the reference range for each serum marker (P?folic acid and vitamins D2 and D3 correlated with the lowest level of homocysteine in T2DM, CVD, and hypertension patients (P?folic acid supplements for reducing the risk of T2DM, CVD, and hypertension in elderly Chinese people, as well as the benefits of vitamin B12 supplements for reducing the risk of CVD alone. PMID:26871790

  18. Neither Folic Acid Supplementation nor Pregnancy Affects the Distribution of Folate Forms in the Red Blood Cells of Women1–3

    PubMed Central

    Hartman, Brenda A.; Fazili, Zia; Pfeiffer, Christine M.; O’Connor, Deborah L.

    2016-01-01

    It is not known whether folate metabolism is altered during pregnancy to support increased DNA and RNA biosynthesis. By using a state-of-the-art LC tandem mass spectrometry technique, the aim of this study was to investigate differences in RBC folate forms between pregnant and nonpregnant women and between nonpregnant women consuming different concentrations of supplemental folic acid. Forms of folate in RBCs were used to explore potential shifts in folate metabolism during early erythropoiesis. Total RBC folate and folate forms [tetrahydrofolate; 5-methyltetrahydrofolate (5-methyl-THF); 4α-hydroxy-5-methyl-tetrahydrofolate (an oxidation product of 5-methyl-THF); 5-formyl-tetrahydrofolate; and 5,10-methenyl-tetrahydrofolate] were measured in 4 groups of women (n = 26): pregnant women (PW) (30–36 wk of gestation) consuming 1 mg/d of folic acid, and nonpregnant women consuming 0 mg/d (NPW-0), 1 mg/d (NPW-1), and 5 mg/d (NPW-5) folic acid. The mean ± SD RBC folate concentration of the NPW-0 group (890 ± 530 nmol/L) was lower than the NPW-1 (1660 ± 350 nmol/L) and NPW-5 (1980 ± 570 nmol/L) groups as assessed by microbiologic assay (n = 26, P < 0.0022). No difference was found between the NPW-1 and NPW-5 groups. We detected 5-methyl-THF [limit of detection (LOD) = 0.06 nmol/L] in all groups and tetrahydrofolate (LOD = 0.2 nmol/L) in most women regardless of methylenetetrahydrofolate reductase genotype. Most women consuming folic acid supplements had detectable concentrations of 5,10-methenyl-tetrahydrofolate (LOD = 0.31 nmol/L). However, there was no difference in the relative distribution of 5-methyl-THF (83–84%), sum of non-methyl folates (0.6–3%), or individual non-methyl folate forms in RBCs across groups. We conclude that although folic acid supplementation in nonpregnant women increases RBC total folate and the concentration of individual folate forms, it does not alter the relative distribution of folate forms. Similarly, distribution of RBC folate forms did not differ between pregnant and nonpregnant women. This trial was registered at clinicaltrials.gov as NCT01741077. PMID:24991041

  19. Single-base resolution of mouse offspring brain methylome reveals epigenome modifications caused by gestational folic acid

    PubMed Central

    2014-01-01

    Background Epigenetic modifications, such as cytosine methylation in CpG-rich regions, regulate multiple functions in mammalian development. Maternal nutrients affecting one-carbon metabolism during gestation can exert long-term effects on the health of the progeny. Using C57BL/6 J mice, we investigated whether the amount of ingested maternal folic acid (FA) during gestation impacted DNA methylation in the offspring’s cerebral hemispheres. Reduced representation bisulfite sequencing at single-base resolution was performed to analyze genome-wide DNA methylation profiles. Results We identified widespread differences in the methylation patterns of CpG and non-CpG sites of key developmental genes, including imprinted and candidate autism susceptibility genes (P <0.05). Such differential methylation of the CpG and non-CpG sites may use different mechanisms to alter gene expressions. Quantitative real time reverse transcription-polymerase chain reaction confirmed altered expression of several genes. Conclusions These finding demonstrate that high maternal FA during gestation induces substantial alteration in methylation pattern and gene expression of several genes in the cerebral hemispheres of the offspring, and such changes may influence the overall development. Our findings provide a foundation for future studies to explore the influence of gestational FA on genetic/epigenetic susceptibility to altered development and disease in offspring. PMID:24484737

  20. Magnetic resonance imaging of folic acid-coated magnetite nanoparticles reflects tissue biodistribution of long-acting antiretroviral therapy

    PubMed Central

    Li, Tianyuzi; Gendelman, Howard E; Zhang, Gang; Puligujja, Pavan; McMillan, JoEllyn M; Bronich, Tatiana K; Edagwa, Benson; Liu, Xin-Ming; Boska, Michael D

    2015-01-01

    Regimen adherence, systemic toxicities, and limited drug penetrance to viral reservoirs are obstacles limiting the effectiveness of antiretroviral therapy (ART). Our laboratory’s development of the monocyte-macrophage-targeted long-acting nanoformulated ART (nanoART) carriage provides a novel opportunity to simplify drug-dosing regimens. Progress has nonetheless been slowed by cumbersome, but required, pharmacokinetic (PK), pharmacodynamics, and biodistribution testing. To this end, we developed a small magnetite ART (SMART) nanoparticle platform to assess antiretroviral drug tissue biodistribution and PK using magnetic resonance imaging (MRI) scans. Herein, we have taken this technique a significant step further by determining nanoART PK with folic acid (FA) decorated magnetite (ultrasmall superparamagnetic iron oxide [USPIO]) particles and by using SMART particles. FA nanoparticles enhanced the entry and particle retention to the reticuloendothelial system over nondecorated polymers after systemic administration into mice. These data were seen by MRI testing and validated by comparison with SMART particles and direct evaluation of tissue drug levels after nanoART. The development of alendronate (ALN)-coated magnetite thus serves as a rapid initial screen for the ability of targeting ligands to enhance nanoparticle-antiretroviral drug biodistribution, underscoring the value of decorated magnetite particles as a theranostic tool for improved drug delivery. PMID:26082630

  1. Folic acid conjugated magnetic iron oxide nanoparticles for nondestructive separation and detection of ovarian cancer cells from whole blood.

    PubMed

    Liu, Wenting; Nie, Liju; Li, Fulai; Aguilar, Zoraida P; Xu, Hong; Xiong, Yonghua; Fu, Fen; Xu, Hengyi

    2016-01-01

    Because of the lack of early screening strategies, ovarian cancer is the most deadly cause of gynecologic malignancies. This paper describes an effective method for the separation and detection of ovarian cancer cells from female whole blood, using folic acid (FA) conjugated magnetic iron oxide nanoparticles (IO-FA nanoparticles). The IO nanoparticles were synthesized by thermal decomposition and then covalently conjugated with FA. The IO-FA nanoparticles were stably attached to the surface of ovarian cancer cells by coupling to the over-expressed folate receptor (FR), thereby making the cells magnetic. These "magnetic cells" were separated from the complex blood matrix without destruction under a magnetic field. The separation efficiency was as high as 61.3% when the abundance of spiked ovarian cancer SKOV3 cells was as low as 5 × 10(-5)%. We also successfully detected five (5) out of ten (10) metastatic ovarian cancer patients' whole blood. This study suggested the feasibility of early detecting of metastatic ovarian cancer cells, which may potentially improve the ovarian cancers patients' overall survival rate for clinical applications. PMID:26478922

  2. An special epithelial staining agents: folic acid receptor-mediated diagnosis (FRD) effectively and conveniently screen patients with cervical cancer

    PubMed Central

    Lu, Meng-Han; Hu, Ling-Yun; Du, Xin-Xin; Yang, Min; Zhang, Wei-Yi; Huang, Ke; Li, Li-An; Jiang, Shu-Fang; Li, Ya-Li

    2015-01-01

    High-quality screening with cytology has markedly reduced mortality from cervical cancer. However, it needs experienced pathologists to review and make the final decisions. We have developed folic acid receptor-mediated diagnosis (FRD) kits to effectively and conveniently screen patients with cervical cancer. We conduct present study aim to assess clinical significances of FRD in screening cervical cancer. A total of 169 patients were enrolled at Chinese People’s liberation Army (PLA) general hospital. We compared diagnostic significances of FRD with thinprep cytology test (TCT). Meanwhile, colposcopy was also performed to confirm any lesion suspicious for cervical cancer. The sensitivity and specificity of FRD were 71.93% and 66.07% in diagnosis cervical cancer, respectively. Meanwhile, the positive predictive values (PPV), negative predictive values (NPV), Youden index were 51.90%, 82.22%, 0.38, respectively. On the other hand, the sensitivity and specificity of TCT in diagnosis cervical cancer were 73.68% and 61.61% respectively. PPV, NPV and Youden index for TCT were 49.41%, 82.14% and 0.35 respectively. Overall, FRD have high values of sensitivity, specificity and Youden index. However, this difference failed to statistical significance. FRD have comparable diagnostic significance with TCT. Therefore, FRD might serve as one effective method to screen cervical cancer. Especially for those patients living in remote regions of China, where cytology was unavailable. PMID:26221336

  3. Folic acid functionalized silver nanoparticles with sensitivity and selectivity colorimetric and fluorescent detection for Hg2+ and efficient catalysis

    NASA Astrophysics Data System (ADS)

    Su, Dongyue; Yang, Xin; Xia, Qingdong; Zhang, Qi; Chai, Fang; Wang, Chungang; Qu, Fengyu

    2014-09-01

    In this research, folic acid functionalized silver nanoparticles (FA-AgNPs) were selected as a colorimetric and a ‘turn on’ fluorescent sensor for detecting Hg2+. After being added into Hg2+, AgNPs can emit stable fluorescence at 440 nm when the excitation wavelength is selected at 275 nm. The absorbance and fluorescence of the FA-AgNPs could reflect the concentration of the Hg2+ ions. Thus, we developed a simple, sensitive analytical method to detect Hg2+ based on the colorimetric and fluorescence enhancement of FA-AgNPs. The sensor exhibits two linear response ranges between absorbance and fluorescence intensity with Hg2+ concentration, respectively. Meanwhile, a detection limit of 1 nM is estimated based on the linear relationship between responses with a concentration of Hg2+. The high specificity of Hg2+ with FA-AgNPs interactions provided the excellent selectivity towards detecting Hg2+ over other metal ions (Pb2+, Mg2+, Zn2+, Ni2+, Cu2+, Co2+, Ca2+, Mn2+, Fe2+, Cd2+, Ba2+, Cr6+ and Cr3+). This will provide a simple, effective and multifunctional colorimetric and fluorescent sensor for on-site and real-time Hg2+ ion detection. The proposed method can be applied to the analysis of trace Hg2+ in lake water. Additionally, the FA-AgNPs can be used as efficient catalyst for the reduction of 4-nitrophenol and potassium hexacyanoferrate (III).

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

    SciTech Connect

    Wu Xiayu; Liang Ziqing; Zou Tianning; Wang Xu

    2009-02-13

    Apoptosis (APO) and necrosis (NEC) are two different types of cell death occurring in response to cellular stress factors. Cells with DNA damage may undergo APO or NEC. Folate is an essential micronutrient associated with DNA synthesis, repair and methylation. Methylenetetrahydrofolate reductase (MTHFR) regulates intracellular folate metabolism. Folate deficiency and MTHFR C677T polymorphisms have been shown to be related to DNA damage. To verify the cytotoxic effects of folate deficiency on cells with different MTHFR C677T genotypes, 15 human peripheral lymphocyte cases with different MTHFR C677T genotypes were cultured in folic acid (FA)-deficient and -sufficient media for 9 days. Cytotoxicity was quantified using the frequencies of APO and NEC as endpoints, the nuclear division index (NDI), and the number of viable cells (NVC). These results showed that FA is an important factor in reducing cytotoxicity and increasing cell proliferation. Lymphocytes with the TT genotype proliferated easily under stress and exhibited different responses to FA deficiency than lymphocytes with the CC and CT genotypes. A TT individual may accumulate more cytotoxicity under cytotoxic stress, suggesting that the effects of FA deficiency on cytotoxicity are greater than the effects in individuals with the other MTHFR C677T variants.

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

    PubMed

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

    2008-06-01

    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

  6. Design and structure activity relationship of tumor-homing histone deacetylase inhibitors conjugated to folic and pteroic acids.

    PubMed

    Sodji, Quaovi H; Kornacki, James R; McDonald, John F; Mrksich, Milan; Oyelere, Adegboyega K

    2015-01-01

    Histone deacetylase (HDAC) inhibition has recently emerged as a novel therapeutic approach for the treatment of various pathological conditions including cancer. Currently, two HDAC inhibitors (HDACi) – Vorinostat and Romidepsin – have been approved for the treatment of cutaneous T-cell lymphoma. However, HDACi remain ineffective against solid tumors and are associated with adverse events including cardiotoxicity. Targeted delivery may enhance the therapeutic indices of HDACi and enable them to be efficacious against solid tumors. We showed herein that morphing of folic and pteroic acids into the surface recognition group of HDACi results in hydroxamate and benzamide HDACi which derived tumor homing by targeting folate receptor (FR), a receptor commonly overexpressed in solid tumors. We observed a correlation between the potency of HDAC1 inhibition and cytotoxicity as only the potent pteroate hydroxamates, 11d and 11e, displayed antiproliferative activity against two representative FR-expression cancer cells. Our observation further supports the previous results which suggest that for a drug to be successfully targeted using the FR, it must be extremely potent against its primary target as the FR has a low delivery efficiency. PMID:25899338

  7. Folic acid-conjugated fluorescent polymer for up-regulation folate receptor expression study via targeted imaging of tumor cells.

    PubMed

    Qiao, Juan; Dong, Ping; Mu, Xiaoyu; Qi, Li; Xiao, Ran

    2016-04-15

    Thoroughly investigation of folate receptor (FR) expression related to targeting drug delivery in tumor cells has been intensively pursued in recent years. Herein, a simple and versatile strategy for determination of FR expression based on targeted imaging of tumor cells with fluorescent nano-conjugates was developed. The fluorescent nano-conjugates were composed of poly 2-vinyl-4,4-dimethyl azlactone (PVDMA) as the linker, folic acid as the targeting unit and amino-Rhodamine B as the fluorescent ligand. Owing to possessing dimethyl azlactone groups in polymer framework, PVDMA could easily reacted with amines or alcohols, and form water soluble materials. Fluorescent imaging studies indicated that the prepared nano-conjugates could specifically target tumor cells and monitor the over expressing of FR. Moreover, the FR expression up-regulation in HeLa cells through medicines regulation has been further explored. This new protocol opens an effective way through synthesis and design of novel fluorescent nano-conjugates for FR expression investigation in tumor cells via targeted imaging, showing great potential in drug delivery mechanism study and cancer therapy. PMID:26606305

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

    NASA Astrophysics Data System (ADS)

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

    2013-04-01

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

  9. Drug targeting to arthritic region via folic acid appended surface-engineered multi-walled carbon nanotubes.

    PubMed

    Kayat, Jitendra; Mehra, Neelesh Kumar; Gajbhiye, Virendra; Jain, Narendra Kumar

    2016-04-01

    This study was aimed at developing and investigating folate anchored carbon nanotubes for targeting an anti-arthritic drug, Methotrexate (MTX) to inflammatory arthritic region. The folic acid (FA) was conjugated to amidated multi-walled carbon nanotubes (MWCNTs) and confirmed by Fourier transform infrared (FTIR), (1)H NMR spectroscopy and X-ray diffraction analysis. The MTX was loaded into the pristine and functionalized-MWCNTs and extensively characterized in vitro and in vivo studies. The drug entrapment efficiency was found high in folate conjugated MWCNTs. In vitro drug release in PBS (pH 7.4) from pristine MWCNTs and folate conjugated MWCNTs formulation was found to be 66.35 ± 2.3 and 56.88 ± 1.9% in 24 h, respectively. Folate conjugated MWCNTs significantly increased (p < 0.005) the percentage inhibition of arthritis, biological half-life and volume of distribution of MTX as compared to MTX-loaded naked MWCNTs as well as free MTX. In in vivo biodistribution studies, MTX was found to be significantly higher (p < 0.005) in arthritic joints from folate functionalized MWCNTs as compared to free drug as well as drug-loaded naked MWCNTs. The present outcomes highlights the propensity of drug-loaded functionalized MWCNTs to alter the pharmacokinetics as well as sustained and targeted drug delivery system as well. PMID:26289435

  10. Intermediate states in the binding process of folic acid to folate receptor α: insights by molecular dynamics and metadynamics.

    PubMed

    Della-Longa, Stefano; Arcovito, Alessandro

    2015-01-01

    Folate receptor α (FRα) is a cell surface, glycophosphatidylinositol-anchored protein which has focussed attention as a therapeutic target and as a marker for the diagnosis of cancer. It has a high affinity for the dietary supplemented folic acid (FOL), carrying out endocytic transport across the cell membrane and delivering the folate at the acidic pH of the endosome. Starting from the recently reported X-ray structure at pH 7, 100 ns classical molecular dynamics simulations have been carried out on the FRα-FOL complex; moreover, the ligand dissociation process has been studied by metadynamics, a recently reported method for the analysis of free-energy surfaces (FES), providing clues on the intermediate states and their energy terms. Multiple dissociation runs were considered to enhance the configurational sampling; a final clustering of conformations within the averaged FES provides the representative structures of several intermediate states, within an overall barrier for ligand escape of about 75 kJ/mol. Escaping of FOL to solvent occurs while only minor changes affect the FRα conformation of the binding pocket. During dissociation, the FOL molecule translates and rotates around a turning point located in proximity of the receptor surface. FOL at this transition state assumes an "L" shaped conformation, with the pteridin ring oriented to optimize stacking within W102 and W140 residues, and the negatively charged glutamate tail, outside the receptor, interacting with the positively charged R103 and R106 residues, that contrary to the bound state, are solvent exposed. We show that metadynamics method can provide useful insights at the atomistic level on the effects of point-mutations affecting functionality, thus being a very promising tool for any study related to folate-targeted drug delivery or cancer therapies involving folate uptake. PMID:25323390

  11. Immunity decreases, antioxidant system damages and tight junction changes in the intestine of grass carp (Ctenopharyngodon idella) during folic acid deficiency: Regulation of NF-κB, Nrf2 and MLCK mRNA levels.

    PubMed

    Shi, Lei; Feng, Lin; Jiang, Wei-Dan; Liu, Yang; Jiang, Jun; Wu, Pei; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu

    2016-04-01

    This investigation used the same growth trial as the previous study, which showed that folic acid deficiency retarded growth in young grass carp (the percent weight gain of Groups 1-6 were 102.32 ± 3.41%, 137.25 ± 10.48%, 179.78 ± 3.95%, 164.33 ± 3.21%, 143.35 ± 8.12% and 115.28 ± 2.66%) [1]. In the present study, we investigated the effects of dietary folic acid on the immune response, antioxidant status and tight junctions in the intestine of young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp were fed diets containing graded levels of folic acid at 0.10, 0.47, 1.03, 1.48, 1.88 and 3.12 mg kg(-1) diet for 8 weeks. The results indicated that acid phosphatase and lysozyme activities, and the complement component 3 content in the proximal intestine (PI), mid intestine (MI) and distal intestine (DI) were decreased with folic acid deficiency (0.1 mg kg(-1)) (P < 0.05). Folic acid deficiency (0.1 mg kg(-1)) up-regulated interleukin 1β, interleukin 8, tumor necrosis factor α, nuclear factor κB p65 (NF-κB p65), IκB kinase α (IKK-α), IKK-β and IKK-γ gene expression, meanwhile down-regulated interleukin 10, transforming growth factor β, IκB and target of rapamycin gene expression in the PI, MI and DI (P < 0.05). These data suggested that folic acid deficiency decreased fish intestinal innate immune function may be partly contributed to the regulation of NF-κB p65 pathway. Moreover, the activities and corresponding gene expression of glutathione content, Cu/Zn superoxide dismutase, catalase, glutathione peroxidase, glutathione s-transferases and glutathione reductase in fish intestine were depressed by deficient folic acid diet (0.1 mg kg(-1)) (P < 0.05). Furthermore, folic acid deficiency (0.1 mg kg(-1)) down-regulated NF-E2-related factor 2 (Nrf2) gene expression, up-regulated Kelch-like-ECH-associated protein 1a (Keap1a) and Keap1b gene expression in fish intestine (P < 0.05). These data indicated that deficient folic acid diet damaged fish intestinal antioxidant capacity partly by regulating Nrf2/Keap1 pathway. Additionally, folic acid deficiency (0.1 mg kg(-1)) down-regulated claudin-b, claudin-c, claudin-3, occludin and zonula occludens 1 gene expression; whereas folic acid deficiency (0.1 mg kg(-1)) up-regulated claudin-12, claudin-15, myosin light chain kinase (MLCK) and p38 mitogen activated protein kinase (p38 MAPK) gene expression in the PI, MI and DI (P < 0.05), suggesting that folic acid deficiency may damage fish intestinal tight junctions associated with the mediation of MLCK and p38 MAPK gene expression. In conclusion, folic acid deficiency (0.1 mg kg(-1)) impaired fish intestinal immunity, antioxidant capacity and tight junctions. PMID:26968494

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

    SciTech Connect

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

    1986-03-05

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

  13. Nuclear abnormalities in buccal mucosa cells of patients with type I and II diabetes treated with folic acid.

    PubMed

    Gómez-Meda, B C; Zamora-Perez, A L; Muñoz-Magallanes, T; Sánchez-Parada, M G; García Bañuelos, J J; Guerrero-Velázquez, C; Sánchez-Orozco, L V; Vera-Cruz, J M; Armendáriz-Borunda, J; Zúñiga-González, G M

    2016-02-01

    Diabetes mellitus (DM) is characterized by high blood glucose. Excessive production of free radicals may cause oxidative damage to DNA and other molecules, leading to complications of the disease. It may be possible to delay or reduce such damage by administration of antioxidants such as folic acid (FA). The objective of this study was to determine the effect of FA on nuclear abnormalities (NAs) in the oral mucosa of patients with DM. NAs (micronucleated cells, binucleated cells, pyknotic nuclei, karyorrhexis, karyolysis, abnormally condensed chromatin, and nuclear buds) were analyzed in 2000 cells from 45 healthy individuals (control group) and 55 patients with controlled or uncontrolled type I or II DM; 35 patients in the latter group were treated with FA. Samples were taken from the FA group before and after treatment. An increased rate of NAs was found in patients with DM in comparison with that of the control group (P<0.001). FA supplementation in patients with DM reduced the frequency of NAs (20.4±8.0 before treatment vs. 10.5±5.2 after treatment; P<0.001). The type I and type II DM and controlled and uncontrolled DM subgroups were analyzed in terms of sex, age, and smoking habit. The significantly reduced frequencies of buccal mucosa cells with micronuclei, binucleation, pyknosis, karyorrhexis, karyorrhexis+abnormally condensed chromatin, karyolysis, and nuclear buds produced by FA supplementation in DM patients (P<0.02) are consistent with the idea that free radicals are responsible for the increased frequency of NAs in DM patients. PMID:26921015

  14. Methylation variation at IGF2 differentially methylated regions and maternal folic acid use before and during pregnancy.

    PubMed

    Hoyo, Cathrine; Murtha, Amy P; Schildkraut, Joellen M; Jirtle, Randy L; Demark-Wahnefried, Wendy; Forman, Michele R; Iversen, Edwin S; Kurtzberg, Joanne; Overcash, Francine; Huang, Zhiqing; Murphy, Susan K

    2011-07-01

    Folic acid (FA) supplementation before and during pregnancy has been associated with decreased risk of neural tube defects although recent reports suggest it may also increase the risk of other chronic diseases. We evaluated exposure to maternal FA supplementation before and during pregnancy in relation to aberrant DNA methylation at two differentially methylated regions (DMRs) regulating Insulin-like Growth Factor 2 (IGF2) expression in infants. Aberrant methylation at these regions has been associated with IGF2 deregulation and increased susceptibility to several chronic diseases. Using a self-administered questionnaire, we assessed FA intake before and during pregnancy in 438 pregnant women. Pyrosequencing was used to measure methylation at two IGF2 DMRs in umbilical cord blood leukocytes. Mixed models were used to determine relationships between maternal FA supplementation before or during pregnancy and DNA methylation levels at birth. Average methylation at the H19 DMR was 61.2%. Compared to infants born to women reporting no FA intake before or during pregnancy, methylation levels at the H19 DMR decreased with increasing FA intake (2.8%, p=0.03, and 4.9%, p=0.04, for intake before and during pregnancy, respectively). This methylation decrease was most pronounced in male infants (p=0.01). Methylation alterations at the H19 DMR are likely an important mechanism by which FA risks and/or benefits are conferred in utero. Because stable methylation marks at DMRs regulating imprinted genes are acquired before gastrulation, they may serve as archives of early exposures with the potential to improve our understanding of developmental origins of adult disease. PMID:21636975

  15. Methylation variation at IGF2 differentially methylated regions and maternal folic acid use before and during pregnancy

    PubMed Central

    Murtha, Amy P; Schildkraut, Joellen M; Jirtle, Randy; Demark-Wahnefried, Wendy; Forman, Michele R; Iversen, Edwin S; Kurtzberg, Joanne; Overcash, Francine; Huang, Zhiqing; Murphy, Susan K

    2011-01-01

    Folic acid (FA) supplementation before and during pregnancy has been associated with decreased risk of neural tube defects although recent reports suggest it may also increase the risk of other chronic diseases. We evaluated exposure to maternal FA supplementation before and during pregnancy in relation to aberrant DNA methylation at two differentially methylated regions (DMRs) regulating insulin-like growth factor 2 (IGF2) expression in infants. Aberrant methylation at these regions has been associated with IGF2 deregulation and increased susceptibility to several chronic diseases. Using a self-administered questionnaire, we assessed FA intake before and during pregnancy in 438 pregnant women. Pyrosequencing was used to measure methylation at two IGF2 DMRs in umbilical cord blood leukocytes. Mixed models were used to determine relationships between maternal FA supplementation before or during pregnancy and DNA methylation levels at birth. Average methylation at the H19 DMR was 61.2%. Compared to infants born to women reporting no FA intake before or during pregnancy, methylation levels at the H19 DMR decreased with increasing FA intake (2.8%, p = 0.03 and 4.9%, p = 0.04, for intake before and during pregnancy, respectively). This methylation decrease was most pronounced in male infants (p = 0.01). Methylation alterations at the H19 DMR are likely an important mechanism by which FA risks and/or benefits are conferred in utero. Because stable methylation marks at DMRs regulating imprinted genes are acquired before gastrulation, they may serve as archives of early exposures with the potential to improve our understanding of developmental origins of adult disease. PMID:21636975

  16. Folic acid deficiency induces premature hearing loss through mechanisms involving cochlear oxidative stress and impairment of homocysteine metabolism

    PubMed Central

    Martínez-Vega, Raquel; Garrido, Francisco; Partearroyo, Teresa; Cediel, Rafael; Zeisel, Steven H.; Martínez-Álvarez, Concepción; Varela-Moreiras, Gregorio; Varela-Nieto, Isabel; Pajares, María A.

    2015-01-01

    Nutritional imbalance is emerging as a causative factor of hearing loss. Epidemiologic studies have linked hearing loss to elevated plasma total homocysteine (tHcy) and folate deficiency, and have shown that folate supplementation lowers tHcy levels potentially ameliorating age-related hearing loss. The purpose of this study was to address the impact of folate deficiency on hearing loss and to examine the underlying mechanisms. For this purpose, 2-mo-old C57BL/6J mice (Animalia Chordata Mus musculus) were randomly divided into 2 groups (n = 65 each) that were fed folate-deficient (FD) or standard diets for 8 wk. HPLC analysis demonstrated a 7-fold decline in serum folate and a 3-fold increase in tHcy levels. FD mice exhibited severe hearing loss measured by auditory brainstem recordings and TUNEL-positive-apoptotic cochlear cells. RT-quantitative PCR and Western blotting showed reduced levels of enzymes catalyzing homocysteine (Hcy) production and recycling, together with a 30% increase in protein homocysteinylation. Redox stress was demonstrated by decreased expression of catalase, glutathione peroxidase 4, and glutathione synthetase genes, increased levels of manganese superoxide dismutase, and NADPH oxidase-complex adaptor cytochrome b-245, α-polypeptide (p22phox) proteins, and elevated concentrations of glutathione species. Altogether, our findings demonstrate, for the first time, that the relationship between hyperhomocysteinemia induced by folate deficiency and premature hearing loss involves impairment of cochlear Hcy metabolism and associated oxidative stress.—Martínez-Vega, R., Garrido, F., Partearroyo, T., Cediel, R., Zeisel, S. H., Martínez-Álvarez, C., Varela-Moreiras, G., Varela-Nieto, I., and Pajares, M. A. Folic acid deficiency induces premature hearing loss through mechanisms involving cochlear oxidative stress and impairment of homocysteine metabolism. PMID:25384423

  17. Folic Acid Promotes Recycling of Tetrahydrobiopterin and Protects Against Hypoxia-Induced Pulmonary Hypertension by Recoupling Endothelial Nitric Oxide Synthase

    PubMed Central

    Chalupsky, Karel; Kračun, Damir; Kanchev, Ivan; Bertram, Katharina

    2015-01-01

    Abstract Aims: Nitric oxide (NO) derived from endothelial NO synthase (eNOS) has been implicated in the adaptive response to hypoxia. An imbalance between 5,6,7,8-tetrahydrobiopterin (BH4) and 7,8-dihydrobiopterin (BH2) can result in eNOS uncoupling and the generation of superoxide instead of NO. Dihydrofolate reductase (DHFR) can recycle BH2 to BH4, leading to eNOS recoupling. However, the role of DHFR and eNOS recoupling in the response to hypoxia is not well understood. We hypothesized that increasing the capacity to recycle BH4 from BH2 would improve NO bioavailability as well as pulmonary vascular remodeling (PVR) and right ventricular hypertrophy (RVH) as indicators of pulmonary hypertension (PH) under hypoxic conditions. Results: In human pulmonary artery endothelial cells and murine pulmonary arteries exposed to hypoxia, eNOS was uncoupled as indicated by reduced superoxide production in the presence of the nitric oxide synthase inhibitor, L-(G)-nitro-L-arginine methyl ester (L-NAME). Concomitantly, NO levels, BH4 availability, and expression of DHFR were diminished under hypoxia. Application of folic acid (FA) restored DHFR levels, NO bioavailability, and BH4 levels under hypoxia. Importantly, FA prevented the development of hypoxia-induced PVR, right ventricular pressure increase, and RVH. Innovation: FA-induced upregulation of DHFR recouples eNOS under hypoxia by improving BH4 recycling, thus preventing hypoxia-induced PH. Conclusion: FA might serve as a novel therapeutic option combating PH. Antioxid. Redox Signal. 23, 1076–1091. PMID:26414244

  18. Use of high doses of folic acid supplements in pregnant women in Spain: an INMA cohort study

    PubMed Central

    Navarrete-Muñoz, Eva María; Valera-Gran, Desirée; García de la Hera, Manoli; Gimenez-Monzo, Daniel; Morales, Eva; Julvez, Jordi; Riaño, Isolina; Tardón, Adonina; Ibarluzea, Jesus; Santa-Marina, Loreto; Murcia, Mario; Rebagliato, Marisa; Vioque, Jesus

    2015-01-01

    Objectives We examined the use of low (<400 μg/day, including no use) and high folic acid supplement (FAS) dosages (≥1000 μg/day) among pregnant women in Spain, and explored factors associated with the use of these non-recommended dosages. Design Population-based cohort study. Setting Spain. Participants We analysed data from 2332 pregnant women of the INMA study, a prospective mother-child cohort study in Spain. Main outcome measures We assessed usual dietary folate and the use of FAS from preconception to the 3rd month (first period) and from the 4th to the 7th month (second period), using a validated food frequency questionnaire. We used multinomial logistic regression to estimate relative risk ratios (RRRs). Results Over a half of the women used low dosages of FAS in the first and second period while 29% and 17% took high dosages of FAS, respectively. In the first period, tobacco smoking (RRR=1.63), alcohol intake (RRR=1.40), multiparous (RRR=1.44), unplanned pregnancy (RRR=4.20) and previous spontaneous abortion (RRR=0.58, lower use of high FAS dosages among those with previous abortions) were significantly associated with low FAS dosages. Alcohol consumption (RRR=1.42), unplanned pregnancy (RRR=2.66) and previous spontaneous abortion (RRR=0.68) were associated with high dosage use. In the second period, only tobacco smoking was significantly associated with high FAS dosage use (RRR=0.67). Conclusions A high proportion of pregnant women did not reach the recommended dosages of FAS in periconception and a considerable proportion also used FAS dosages ≥1000 μg/day. Action should be planned by the Health Care System and health professionals to improve the appropriate periconceptional use of FAS, taking into consideration the associated factors. PMID:26603248

  19. 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

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

    2014-01-01

    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. PMID:25003120

  20. 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

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

    2014-01-01

    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. PMID:25003120

  1. Cytotoxicity of folic acid conjugated hollow silica nanoparticles toward Caco2 and 3T3 cells, with and without encapsulated DOX.

    PubMed

    Patel, Kunal; Sundara Raj, Behin; Chen, Yan; Lou, Xia

    2016-04-01

    Hollow silica nanoparticles of two sizes with and without a folic acid targeting ligand were synthesized. Fickian diffusion of the antitumor drug doxorubicin hydrochloride (DOX) was demonstrated by the produced nanoparticles, achieving a cumulative release of 73% and 45% for 215nm and 430nm particles respectively over a period of 500h. The hollow silica nanoparticles presented a time and dose dependent toxicity, selective to human epithelial colorectal adenocarcinoma (Caco2) cells, over mouse embryonic fibroblast (3T3) cells. At 24h Caco2 cell viability was reduced to 66% using pure hollow silica at a concentration of 50μgmL(-1), while that of 3T3 cells remained at 94% under the same conditions. The selective cytotoxicity of hollow silica nanoparticles was further enhanced by conjugation of folic acid and incorporation of DOX: at 24h and an equivalent DOX concentration of 0.5μgmL(-1), viable Caco2 cells were reduced to 45% while 3T3 cells were reduced to 83%. Interestingly the equivalent dose of free DOX was more toxic to 3T3 than to Caco2 cells, reducing the 3T3 viability to 72% and the Caco2 viability to 80%, which is likely due to the presence of the p-glycoprotein pumps in Caco2 cells. Folic acid conjugation served to enhance the viability of both cell lines in this work. Careful optimization of the folate content should further improve the cell specificity of the hollow silica nanoparticles, thus providing a viable targeting platform for cancer therapy. PMID:26764104

  2. Long-Term Weekly Iron-Folic Acid and De-Worming Is Associated with Stabilised Haemoglobin and Increasing Iron Stores in Non-Pregnant Women in Vietnam

    PubMed Central

    Casey, Gerard J.; Jolley, Damien; Phuc, Tran Q.; Tinh, Ta T.; Tho, Dang H.; Montresor, Antonio; Biggs, Beverley-Ann

    2010-01-01

    Background The prevalence of anaemia and iron deficiency in women remains high worldwide. WHO recommends weekly iron-folic acid supplementation where anaemia rates in non-pregnant women of reproductive age are higher than 20%. In 2006, a demonstration project consisting of weekly iron-folic acid supplementation and regular de-worming was set up in two districts in a northern province in Vietnam where anaemia and hookworm rates were 38% and 76% respectively. In 2008 the project was expanded to all districts in the province, targeting some 250,000 women. The objectives of this study were to: 1) examine changes in haemoglobin, iron stores and soil transmitted helminth infection prevalence over three years and 2) assess women's access to and compliance with the intervention. Methods and Findings The study was a semi-cross-sectional, semi-longitudinal panel design with a baseline survey, three impact surveys at three-, twelve- and thirty months after commencement of the intervention, and three compliance surveys after ten weeks, eighteen and thirty six months. Results After thirty months, mean haemoglobin stabilised at 130.3 g/L, an increase of 8.2 g/L from baseline, and mean serum ferritin rose from 23.9 µg/L to 52 µg/L. Hookworm prevalence fell from 76% to 22% over the same period. After thirty six months, 81% of the target population were receiving supplements and 87% were taking 75% or more of the supplements they received. Conclusions Weekly iron-folic acid supplementation and regular de-worming was effective in significantly and sustainably reducing the prevalence of anaemia and soil transmitted helminth infections and high compliance rates were maintained over three years. PMID:21209902

  3. Lower Risk of Cervical Intraepithelial Neoplasia in Women with High Plasma Folate and Sufficient Vitamin B12 in the Post-Folic Acid Fortification Era

    PubMed Central

    Piyathilake, Chandrika J.; Macaluso, Maurizio; Alvarez, Ronald D.; Bell, Walter C.; Heimburger, Douglas C.; Partridge, Edward E.

    2016-01-01

    The purpose of this study was to determine the influence of plasma folate and vitamin B12 concentrations on cervical cancer risk in the U.S. after the folic acid fortification era. The study included 376 premenopausal women of childbearing age who tested positive for infections with high-risk (HR) human papillomaviruses (HPVs) and were diagnosed with cervical intraepithelial neoplasia (CIN) grade 2 or higher (CIN 2+, cases) or ≤CIN 1 (noncases). CIN 2+ (yes/no) was the dependent variable in logistic regression models that specified plasma folate concentrations combined with plasma B12 concentrations as the independent predictors of primary interest, adjusting for age, race, education, smoking, parity, number of lifetime male sexual partners, use of contraceptives, waist circumference, physical activity, healthy eating index, and circulating concentrations of vitamins A, C, tocopherol, and total carotene. Women with supraphysiologic concentrations of plasma folate (>19.8 ng/mL) who also had sufficient plasma vitamin B12 (≥200.6 pg/mL) had 70% lower odds of being diagnosed with CIN 2+ (P = 0.04) when compared with women with plasma folate of ≤19.8 ng/mL and plasma vitamin B12 of <200.6 pg/mL. Our results do not corroborate the concern that supraphysiologic plasma folate concentrations seen in the post-U.S. folic acid fortification era increase the risk of CIN in premenopausal women of childbearing age. In fact, higher folate is associated with significantly lower risk of CIN, especially when vitamin B12 is sufficient, demonstrating the importance of vitamin B12 in the high-folate environment created by the folic acid fortification program. PMID:19542191

  4. 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

    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

    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. PMID:23593517

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

    PubMed

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

    2006-09-01

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

  6. Size control in the synthesis of 1-6 nm gold nanoparticles using folic acid-chitosan conjugate as a stabilizer

    NASA Astrophysics Data System (ADS)

    Liu, Lili; Zhang, Xianwen; Chaudhuri, Jharna

    2014-09-01

    We report a simple and practical method for the preparation of folic acid (FA)-chitosan functionalized gold nanoparticles (AuNPs) with a very small size (1-6 nm). Sodium borohydride was used as a reducing agent. The size of the AuNPs was controlled by adjusting the mass fraction of FA-chitosan conjugate to Au. The AuNPs were characterized using UV-vis spectroscopy and transmission electron microscopy (TEM). The results indicated that the size distribution of AuNPs decreased ranging from 6 nm to 1 nm with increasing the fraction of FA-chitosan conjugate in the reaction systems.

  7. Determining the Effect of Gutkha on Serum Levels of Vitamin B12 and Folic Acid as Compared to Smoking among Chronic Periodontitis Subjects : A Cross-Sectional Study

    PubMed Central

    Warad, Shivaraj; Kalburgi, Nagaraj B; Kalburgi, Veena C; Koregol, Arati C; Patanashetti, Jyoti; Rao, Subramaniam; Kokatnur, M. Vijayalaxmi

    2014-01-01

    Background: Periodontitis, being a common inflammatory disease has a multifactorial origin , with smoking and gutkha as few of the causative entities. The role of smoking as a risk factor for periodontitis is been well documented in literature. Cigarette smoke also affects vitamin B12 and folic acid mechanisms. Nutritionally derived vitamin B12 occurs mainly as either hydroxycobalamin or deoxyadenosycobalmin. Folic acid is also heat sensitive and water soluble, closely linked to vitamin B12 in its metabolism. However, effect of smokeless tobacco in form of gutkha on serum levels of vitamin B12 and folic acid is yet to be explored. Aims and Objectives: To estimate and correlate serum vitamin B12 (VB12) and folic acid (FA) levels among periodontally healthy subjects and Chronic Periodontitis (CP) subjects with habit of smoking and gutkha chewing. Materials and Methods: The study included 111 subjects ranging in age from 18 to 60 y. Participants were divided into four groups: 30 healthy subjects (Group I), 29 subjects with CP (Group II), 25 smokers with CP (Group III) and 27 gutkha chewers with CP (Group IV). Clinical parameters included pocket probing depth (PPD), clinical attachment level (CAL) & gingival index (GI) following which VB12 and FA levels were estimated through UV-spectrophotometry method and data was analysed using Statistical Package for Social Scientists software, Mann-Whitney U-test and Pearson correlation coefficient. p-values less than 0.05 were considered as significant. Results : Pairwise comparison by Mann-Whitney U-test showed an increase in the serum VB12 in Group IV when compared to Group I (p=0.01) and Group II (p=0.01). Although serum FA levels were found to be low in Group III (7.61 ug/ml) & Group IV (8.64 ug/ml), Group III was found to be statistically significant (P=0.046). The clinical parameters GI, PPD and CAL among the four groups of patients were also statistically significant (p < 0.05). Conclusion: The study results suggested that among the patients with periodontal disease, serum VB12 levels are directly related while serum FA levels are inversely related to inflammation and tissue destruction in periodontium as occurred in Group IV. PMID:25654040

  8. First report on hemoglobin electrostatic immobilization on WO3 nanoparticles: application in the simultaneous determination of levodopa, uric acid, and folic acid.

    PubMed

    Ghodsi, Javad; Rafati, Amir Abbas; Shoja, Yalda

    2016-05-01

    This work describes the first report about the simultaneous determination of levodopa (L-DOPA) with folic acid (FA) and uric acid (UA) based on electrocatalytic oxidation of L-DOPA with peroxidase properties of hemoglobin (Hb) in the presence of H2O2 as Hb activator. Bovine Hb was electrostatically immobilized on WO3 nanoparticles (WO3NPs) in pH between Hb and WO3NP isoelectric points, and subsequently, a carbon paste electrode (CPE) was modified with the obtained WO3NPs-Hb and multiwalled carbon nanotubes (MWCNTs). The resulting biosensor supplied a sensitive and suitably stable biosensor for the simultaneous determination of L-DOPA, UA, and FA. The obtained linear range and detection limit for L-DOPA, UA, and FA were completely acceptable, and the biosensor response time for these molecules was relatively short so that it reaches about 95 % of its maximum response in less than 10 s. The applicability of the current biosensor was confirmed with the determination of L-DOPA in the presence of fixed amounts of FA and UA in some real samples by the standard addition method. PMID:27007733

  9. Homocysteine, folic acid and vitamin B12 in relation to pre- and postnatal health aspects.

    PubMed

    Obeid, Rima; Herrmann, Wolfgang

    2005-01-01

    Studies linking hyperhomocysteinemia (HHCY) and B-vitamin deficiency to some health aspects in children have been accumulating. Low B-vitamin status inearly life, even as early as the time of conception, may endanger the potential for new life and may negatively influence the health of the offspring. Early abortion, pregnancy complications and poor pregnancy outcomes have been linked to elevated concentrations of total plasma homocysteine (tHcy) and low folate or vitamin B12. Maternal vitamin status predicts that of fetuses and neonates. Lactating women are likely to experience low micronutrient status, which might affect breast-milk composition and hence the nutritional status of their breast-fed infants. Elevated concentrations of methylmalonic acid (MMA) is common in infants (age <6 months), which may indicate a transient inadequate vitamin B12 status. Deficiency of B-vitamins might confer deleterious effects on the physical and mental health of the child, such as impaired growth, gross motor function, poor school performance and other adaptive skills. The importance of maintaining adequate B-vitamin status during periods of progressive growth and development should be emphasized because symptoms related to folate and vitamin B12 deficiency are difficult to detect. Serum levels of tHcy and MMA should be estimated in several target groups of children, pregnant and lactating women and those planning for pregnancy. Concentrations of tHcy and MMA are useful indicators of B-vitamin status in the pediatric laboratory. Using these functional markers may facilitate detecting sub-optimal B-vitamin status in children. PMID:16197297

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

    PubMed Central

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

    2014-01-01

    Background Studies have indicated that altered maternal micronutrients and vitamins influence the development of newborns and altered nutrient exposure throughout the lifetime may have potential health effects and increased susceptibility to chronic diseases. In recent years, folic acid (FA) exposure has significantly increased as a result of mandatory FA fortification and supplementation during pregnancy. Since FA modulates DNA methylation and affects gene expression, we investigated whether the amount of FA ingested during gestation alters gene expression in the newborn cerebral hemisphere, and if the increased exposure to FA during gestation and throughout the lifetime alters behavior in C57BL/6J mice. Methods Dams were fed FA either at 0.4 mg or 4 mg/kg diet throughout the pregnancy and the resulting pups were maintained on the diet throughout experimentation. Newborn pups brain cerebral hemispheres were used for microarray analysis. To confirm alteration of several genes, quantitative RT-PCR (qRT-PCR) and Western blot analyses were performed. In addition, various behavior assessments were conducted on neonatal and adult offspring. Results Results from microarray analysis suggest that the higher dose of FA supplementation during gestation alters the expression of a number of genes in the newborns’ cerebral hemispheres, including many involved in development. QRT-PCR confirmed alterations of nine genes including down-regulation of Cpn2, Htr4, Zfp353, Vgll2 and up-regulation of Xist, Nkx6-3, Leprel1, Nfix, Slc17a7. The alterations in the expression of Slc17a7 and Vgll2 were confirmed at the protein level. Pups exposed to the higher dose of FA exhibited increased ultrasonic vocalizations, greater anxiety-like behavior and hyperactivity. These findings suggest that although FA plays a significant role in mammalian cellular machinery, there may be a loss of benefit from higher amounts of FA. Unregulated high FA supplementation during pregnancy and throughout the life course may have lasting effects, with alterations in brain development resulting in changes in behavior. PMID:25006883

  11. Periconceptional folic acid supplementation and anthropometric measures at birth in a cohort of pregnant women in Valencia, Spain.

    PubMed

    Pastor-Valero, Maria; Navarrete-Muñoz, Eva Maria; Rebagliato, Marisa; Iñiguez, Carmen; Murcia, Mario; Marco, Alfredo; Ballester, Ferran; Vioque, Jesus

    2011-05-01

    We examined the relationship between dietary folate intake and periconceptional use of folic acid (FA) supplements, and small-for-gestational age for weight (SGA-W) and height (SGA-H). The study is based on 786 Spanish women aged 16 years or above, who attended the first-term prenatal population-based screening programme (10-13 weeks) at the reference hospital 'La Fe', Valencia, with singleton pregnancy. Periconceptional use of FA supplements was categorised as non-users, moderate users ( ≤ 1 mg/d) and high users (>1 mg/d). Babies born to mothers who used high doses of FA supplements had a significant reduction in mean birth height compared with babies of non-users (β = - 0·53, 95 % CI - 0·96, - 0·09). As regards weight, mothers using moderate and high doses of FA supplements had lower-birth-weight babies for gestational age than non-users (β = - 22·96, 95 % CI - 101·14, 55·23; β = - 89·72, 95 % CI - 188·64, 9·21, respectively), although these decreases were not significant. Results from the multivariate logistic regression models showed that high FA supplement users had a higher significant risk for SGA-H (OR 5·33, 95 % CI 2·08, 13·7), and that users of moderate doses were not associated with a higher risk of either a SGA-W or a SGA-H baby. In contrast, increased quintiles of the dietary intake of folate were associated with a decreased risk of SGA-W (P for trend = 0·002), although no association was observed for SGA-H. Our findings suggest that periconceptional use of FA supplements greater than 1 mg/d is associated with decreased birth height and may entail a risk of decreased birth weight. PMID:21272409

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

    PubMed Central

    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

    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 β-CD based drug complex might be promising as an anti-tumor treatment for FR(+) cancer. PMID:23658721

  13. Phytosynthesis of gold nanoparticles using Mappia foetida leaves extract and their conjugation with folic acid for delivery of doxorubicin to cancer cells.

    PubMed

    Yallappa, S; Manjanna, J; Dhananjaya, B L; Vishwanatha, U; Ravishankar, B; Gururaj, H

    2015-09-01

    Mappia foetida leaves extract is used as bioreductant for the synthesis of gold nanoparticles and their application in the efficient delivery of doxorubicin to human cancer cells is reported here. The formation of gold nanoparticles is evident from their characteristic optical absorption at ~560 nm. X-ray diffraction pattern of gold nanoparticles confirmed their fcc structure. Fourier transform infrared spectroscopy shows the bioactive molecules from plant extract capped on the surface of gold nanoparticles and conjugation of doxorubicin along with activated folic acid as navigational molecules for targeted drug delivery. Such a conjugation of gold nanoparticles is characterized by their weight loss, ~35-40 %, due to thermal degradation of plant biomass and conjugated drug along with receptor, as observed in thermogravimetric analysis. The spherical shaped gold nanoparticles (Φ 10-20 nm) are observed by field emission scanning electron microscopy and transmission electron microscopy images and the expected elemental composition by energy dispersive X-ray spectroscopy. Gold nanoparticles conjugated with activated folic acid and doxorubicin complex is found to be toxic for human cancer cells viz., MDA-MB-231, HeLa, SiHa and Hep-G2. Furthermore, the amount of drug released was maximum at pH 5.3 (an ambient condition for intravenous cancer drugs) followed by pH 7.2 and pH 6.8. PMID:26395360

  14. High Gestational Folic Acid Supplementation Alters Expression of Imprinted and Candidate Autism Susceptibility Genes in a sex-Specific Manner in Mouse Offspring.

    PubMed

    Barua, Subit; Kuizon, Salomon; Ted Brown, W; Junaid, Mohammed A

    2016-02-01

    Maternal nutrients play critical roles in modulating epigenetic events and exert long-term influences on the progeny's health. Folic acid (FA) supplementation during pregnancy has decreased the incidence of neural tube defects in newborns, but the influence of high doses of maternal FA supplementation on infants' brain development is unclear. The present study was aimed at investigating the effects of a high dose of gestational FA on the expression of genes in the cerebral hemispheres (CHs) of 1-day-old pups. One week prior to mating and throughout the entire period of gestation, female C57BL/6J mice were fed a diet, containing FA at either 2 mg/kg (control diet (CD)) or 20 mg/kg (high maternal folic acid (HMFA)). At postnatal day 1, pups from different dams were sacrificed and CH tissues were collected. Quantitative RT-PCR and Western blot analysis confirmed sex-specific alterations in the expression of several genes that modulate various cellular functions (P < 0.05) in pups from the HMFA group. Genomic DNA methylation analysis showed no difference in the level of overall methylation in pups from the HMFA group. These findings demonstrate that HMFA supplementation alters offsprings' CH gene expression in a sex-specific manner. These changes may influence infants' brain development. PMID:26547318

  15. The effects of feeding rats diets deficient in folic acid and related methyl donors on the blood pressure and glucose tolerance of the offspring.

    PubMed

    Maloney, Christopher A; Hay, Susan M; Rees, William D

    2009-05-01

    In humans poor maternal folate status is associated with a decrease in infant birth weight. As low birth weight increases the risk of cardiovascular and metabolic disease in adults, an inadequate supply of folic acid in the mother's diet may increase the susceptibility of the offspring to disease. We have fed laboratory rats diets deficient in folic acid and the related methyl donors methionine and choline to examine the effects on growth, blood pressure and insulin action in the offspring. Poor folate status transiently increased fetal growth but did not produce a long-term change in body weight. There were, however, small changes in the hearts of the female offspring. When folate deficiency was combined with low intakes of methionine and choline, the kidneys of the male offspring were proportionately smaller, probably because of the limited availability of methionine. There was no effect on the blood pressure of either the male or female offspring. The pancreatic insulin content of fetuses from animals fed the folate-deficient diets were higher than those of the controls. Following an oral glucose challenge, there was a weak trend for glucose-stimulated insulin release to be increased in the offspring of dams fed the folate-deficient diet. The changes in insulin concentrations were, however, much smaller than the corresponding changes observed in the offspring of animals fed protein-deficient diets. These results suggest that folate deficiency during gestation causes modest changes to the insulin axis of the fetus. PMID:18782463

  16. Maternal Folic Acid Supplementation and the Risk of Congenital Heart Defects in Offspring: A Meta-Analysis of Epidemiological Observational Studies

    PubMed Central

    Feng, Yu; Wang, Song; Chen, Runsen; Tong, Xing; Wu, Zeyu; Mo, Xuming

    2015-01-01

    Epidemiological studies have reported conflicting results regarding the association between maternal folic acid supplementation and the risk of congenital heart defects (CHDs). However, a meta-analysis of the association between maternal folic acid supplementation and CHDs in offspring has not been conducted. We searched the MEDLINE and EMBASE databases for articles cataloged between their inceptions and October 10, 2014 and identified relevant published studies that assessed the association between maternal folate supplementation and the risk of CHDs. Study-specific relative risk estimates were pooled using random-effects or fixed-effects models. Out of the 1,606 articles found in our initial literature searches, a total of 1 randomized controlled trial, 1 cohort study, and 16 case-control studies were included in our final meta-analysis. The overall results of this meta-analysis provide evidence that maternal folate supplementation is associated with a significantly decreased risk of CHDs (RR = 0.72, 95% CI: 0.63–0.82). Statistically significant heterogeneity was detected (Q = 82.48, P < 0.001, I2 = 79.4%). We conducted stratified and meta-regression analyses to identify the origin of the heterogeneity among the studies, and a Galbraith plot was generated to graphically assess the sources of heterogeneity. This meta-analysis provides a robust estimate of the positive association between maternal folate supplementation and a decreased risk of CHDs. PMID:25687545

  17. Maternal Folic Acid Supplementation and the Risk of Congenital Heart Defects in Offspring: A Meta-Analysis of Epidemiological Observational Studies

    NASA Astrophysics Data System (ADS)

    Feng, Yu; Wang, Song; Chen, Runsen; Tong, Xing; Wu, Zeyu; Mo, Xuming

    2015-02-01

    Epidemiological studies have reported conflicting results regarding the association between maternal folic acid supplementation and the risk of congenital heart defects (CHDs). However, a meta-analysis of the association between maternal folic acid supplementation and CHDs in offspring has not been conducted. We searched the MEDLINE and EMBASE databases for articles cataloged between their inceptions and October 10, 2014 and identified relevant published studies that assessed the association between maternal folate supplementation and the risk of CHDs. Study-specific relative risk estimates were pooled using random-effects or fixed-effects models. Out of the 1,606 articles found in our initial literature searches, a total of 1 randomized controlled trial, 1 cohort study, and 16 case-control studies were included in our final meta-analysis. The overall results of this meta-analysis provide evidence that maternal folate supplementation is associated with a significantly decreased risk of CHDs (RR = 0.72, 95% CI: 0.63-0.82). Statistically significant heterogeneity was detected (Q = 82.48, P < 0.001, I2 = 79.4%). We conducted stratified and meta-regression analyses to identify the origin of the heterogeneity among the studies, and a Galbraith plot was generated to graphically assess the sources of heterogeneity. This meta-analysis provides a robust estimate of the positive association between maternal folate supplementation and a decreased risk of CHDs.

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

    NASA Astrophysics Data System (ADS)

    Hwang, Sun-Young

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

  19. Maternal diets deficient in folic acid and related methyl donors modify mechanisms associated with lipid metabolism in the fetal liver of the rat.

    PubMed

    McNeil, Christopher J; Hay, Susan M; Rucklidge, Garry J; Reid, Martin D; Duncan, Gary J; Rees, William D

    2009-11-01

    Previously we have examined the effects of diets deficient in folic acid ( - F) or folate deficient with low methionine and choline ( - F LM LC) on the relative abundance of soluble proteins in the liver of the pregnant rat. In the present study we report the corresponding changes in the fetal liver at day 21 of gestation. The abundance of eighteen proteins increased when dams were fed the - F diet. When dams were fed the - F LM LC diet, thirty-three proteins increased and eight decreased. Many of the differentially abundant proteins in the fetal liver could be classified into the same functional groups as those previously identified in the maternal liver, namely protein synthesis, metabolism, lipid metabolism and proteins associated with the cytoskeleton and endoplasmic reticulum. The pattern was consistent with reduced cell proliferation in the - F LM LC group but not in the - F group. Metabolic enzymes associated with lipid metabolism changed in both the - F and - F LM LC groups. The mRNA for carnitine palmitoyl transferase were up-regulated and CD36 (fatty acid translocase) down-regulated in the - F group, suggesting increased mitochondrial oxidation of fatty acids as an indirect response to altered maternal lipid metabolism. In the - F LM LC group the mRNA for acetyl CoA carboxylase was down-regulated, suggesting reduced fatty acid synthesis. The mRNA for transcriptional regulators including PPARalpha and sterol response element-binding protein-1c were unchanged. These results suggest that an adequate supply of folic acid and the related methyl donors may benefit fetal development directly by improving lipid metabolism in fetal as well as maternal tissues. PMID:19566968

  20. Folic Acid and Pregnancy

    MedlinePlus

    ... added to enriched grain products — so you can boost your intake by looking for breakfast cereals, breads, ... your body — and, therefore, your baby — an added boost of vitamins and minerals. Some health care providers ...

  1. Folic acid in diet

    MedlinePlus

    ... as pregnancy and illnesses, are also important. The Food and Nutrition Board of the Institute of Medicine Recommended Intakes ... For infants from birth to 12 months, the Food and Nutrition Board established an Acceptable Intake (AI) for folate ...

  2. Folic acid and its photoproducts, 6-formylpterin and pterin-6-carboxylic acid, as generators of reactive oxygen species in skin cells during UVA exposure.

    PubMed

    Juzeniene, Asta; Grigalavicius, Mantas; Ma, Li Wei; Juraleviciute, Marina

    2016-02-01

    Folic acid (FA) is the synthetic form of folate (vitamin B9), present in supplements and fortified foods. During ultraviolet (UV) radiation FA is degraded to 6-formylpterin (FPT) and pterin-6-carboxylic acid (PCA) which generate reactive oxygen species (ROS) and may be phototoxic. The aim of the present study was to investigate the production of ROS and phototoxicity of FA, FPT and PCA in skin cells during UVA exposure. The production of ROS and phototoxicity of FA, FPT and PCA were studied in the immortal human keratinocytes (HaCaT) and malignant skin cells (A431 and WM115) during UVA exposure. Increased ROS production and the photoinactivation of cells in vitro were observed during UVA exposure in the presence of FA, FPT and PCA. HPLC analysis revealed that 10μM FA photodegradation was around 2.1 and 5.8-fold faster than that of 5μM and 1μM FA. Photodegradation of FA is concentration dependent, and even non-phototoxic doses of FA and its photoproducts, FPT and PCA, generate high levels of ROS in vitro. FA, FPT and PCA are phototoxic in vitro. The photodegradation of topical or unmetabolized FA during UV exposure via sunlight, sunbeds or phototherapy may lead to ROS production, to the cutaneous folate deficiency, skin photocarcinogenesis and other deleterious skin effects. Further studies are needed to confirm whether UV exposure can decrease cutaneous and serum folate levels in humans taking FA supplements or using cosmetic creams with FA. PMID:26780587

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

    PubMed

    Girard, C L; Matte, J J

    2005-02-01

    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

  4. The hepatic Igf2/H19 locus is not altered in 1-day old pups born to obese-prone Sprague-Dawley rats fed a low protein diet containing adequate folic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gong et al. (Epigenetics, 2010) found, using diets low in folic acid, that compared to an 18% protein diet a 9% protein diet fed to pregnant Sprague-Dawley rats resulted in increased Igf2 and H19 gene expression in the liver of day 0 male offspring. In addition DNA methylation in the Imprinting Cont...

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

    PubMed Central

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

    2013-01-01

    Background Adequate folate supplementation in the periconceptional phase is recommended to reduce the risk of neural tube defects. Oral contraceptives may provide a reasonable delivery vehicle for folate supplementation before conception in women of childbearing potential. This study aimed to demonstrate that a fixed-dose combination of an oral contraceptive and levomefolate calcium leads to sustainable improvements in folate status compared with an oral contraceptive + folic acid. Methods This was a double-blind, randomized, parallel-group study in which 172 healthy women aged 1840 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 812 weeks) after cessation of EE-drospirenone-levomefolate calcium treatment. Plasma and RBC folate levels remained above baseline values in 41.3% and 89.3% of women, respectively, at the end of the 20-week elimination phase. Conclusion Improvements in folate status were comparable between EE-drospirenone-levomefolate calcium and EE-drospirenone + folic acid. Plasma and RBC folate levels remained elevated for several months following cessation of treatment with EE-drospirenone-levomefolate calcium. PMID:23610531

  6. 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

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

    2009-02-01

    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

  7. Gene polymorphisms as risk factors for predicting the cardiovascular manifestations in Marfan syndrome. Role of folic acid metabolism enzyme gene polymorphisms in Marfan syndrome.

    PubMed

    Benke, Kálmán; Ágg, Bence; Mátyás, Gábor; Szokolai, Viola; Harsányi, Gergely; Szilveszter, Bálint; Odler, Balázs; Pólos, Miklós; Maurovich-Horvat, Pál; Radovits, Tamás; Merkely, Béla; Nagy, Zsolt B; Szabolcs, Zoltán

    2015-10-01

    Folic acid metabolism enzyme polymorphisms are believed to be responsible for the elevation of homocysteine (HCY) concentration in the blood plasma, correlating with the pathogenesis of aortic aneurysms and aortic dissection. We studied 71 Marfan patients divided into groups based on the severity of cardiovascular involvement: no intervention required (n=27, Group A); mild involvement requiring intervention (n=17, Group B); severe involvement (n=27, Group C) subdivided into aortic dilatation (n=14, Group C1) and aortic dissection (n=13, Group C2), as well as 117 control subjects. We evaluated HCY, folate, vitamin B12 and the polymorphisms of methylenetetrahydrofolate reductase (MTHFR;c.665C>T and c.1286A>C), methionine synthase (MTR;c.2756A>G) and methionine synthase reductase (MTRR;c.66A>G). Multiple comparisons showed significantly higher levels of HCY in Group C2 compared to Groups A, B, C1 and control group (p<0.0001, p<0.0001, p=0.001 and p=0.003, respectively). Folate was lower in Group C2 than in Groups A, B, C1 and control subjects (p<0.0001, p=0.02, p<0.0001 and p<0.0001, respectively). Group C2 had the highest prevalence of homozygotes for all four gene polymorphisms. Multivariate logistic regression analysis revealed that HCY plasma level was an independent risk factor for severe cardiovascular involvement (Group C; odds ratio [OR] 1.85, 95% confidence interval [CI] 1.28-2.67, p=0.001) as well as for aortic dissection (Group C2; OR 2.49, 95%CI 1.30-4.78, p=0.006). In conclusion, severe cardiovascular involvement in Marfan patients, and especially aortic dissection, is associated with higher HCY plasma levels and prevalence of homozygous genotypes of folic acid metabolism enzymes than mild or no cardiovascular involvement. These results suggest that impaired folic acid metabolism has an important role in the development and remodelling of the extracellular matrix of the aorta. PMID:26063524

  8. Fabrication and spectroscopic studies of folic acid-conjugated Fe3O4@Au core-shell for targeted drug delivery application.

    PubMed

    Karamipour, Sh; Sadjadi, M S; Farhadyar, N

    2015-09-01

    Gold coated magnetite core shell is a kind of nanoparticle that include magnetic iron oxide core with a thin layer nanogold. Fe3O4-gold core-shell nanostructure can be used in biomedical applications such as magnetic bioseparation, bioimaging, targeting drug delivery and cancer treatment. In this study, the synthesis and characterization of gold coated magnetite nanoparticles were discussed. Magnetite nanoparticles with an average size of 6 nm in diameter were synthesized by the chemical co-precipitation method and gold-coated Fe3O4 core-shell nanostructures were produced with an average size of 11.5 nm in diameter by reduction of Au(3+) with citrate ion in the presence of Fe3O4. Folate-conjugated gold coated magnetite nanoparticles were synthesized to targeting folate receptor that is overexpressed on the surface of cancerous cells. For this purpose, we used l-cysteine, as a bi-functional linker for attachment to gold surface and it was linked to the gold nanoparticles surface through its thiol group. Then, we conjugated amino-terminated nanoparticles to folic acid with an amide-linkage formation. These gold magnetic nanoparticles were characterized by various techniques such as X-ray powder diffraction (XRD) analysis, Fourier transform infrared spectrometer (FT-IR), UV-visible spectroscopy, transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), dispersive analysis of X-ray (EDAX) and vibrating sample magnetometer (VSM) analysis. The magnetic and optical properties of Fe3O4 nanostructure were changed by gold coating and attachment of l-cysteine and folic acid to Fe3O4@Au nanoparticles. PMID:25879984

  9. Effectiveness and Feasibility of Weekly Iron and Folic Acid Supplementation to Adolescent Girls and Boys through Peer Educators at Community Level in the Tribal Area of Gujarat

    PubMed Central

    Shah, Shobha P; Shah, Pankaj; Desai, Shrey; Modi, Dhiren; Desai, Gaytri; Arora, Honey

    2016-01-01

    Background: Anemia during adolescence affects growth and development of girls and boys increasing their vulnerability to dropping out-of-school. Hence investing in preventing anemia during adolescence is critical for their survival, growth and development. Objective: To find out the burden of anemia on adolescent age group in the tribal area of Jhagadia block and to assess the change in the hemoglobin level through the weekly Iron and Folic Acid IFA (DOTS) directly observed treatment supplementation under Supervision by Peer Educators at Community level among adolescents. Methods: Community based intervention study conducted with adolescents (117 girls and 127 boys) aged 10-19 years, through supplementation of IFA (DOTS) by trained Peer Educators for 52 weeks in 5 tribal villages of Jhagadia. Hemoglobin level was determined by HemoCue method before and after intervention and sickle cell anemia by Electrophoresis method. Primary data on hemoglobin and number of tablets consumed was collected and statistically analyzed in SPSS 16.0 software by applying paired t-test. Results: The overall findings suggest that the prevalence of anemia reduced from 79.5% to 58% among adolescent girls and from 64% to 39% among boys. Mean rise of hemoglobin seen was 1.5 g/dl among adolescent boys and 1.3 g/dl among girls. A significant association was found in change in hemoglobin before and after intervention (P = 0.000) Conclusion: Prevalence of anemia among girls and boys can be reduced in their adolescent phase of life, through weekly supplementation of iron folic acid tablets under direct supervision and Nutrition Education by Peer Educator at community level. PMID:27051093

  10. Weekly Iron-Folic Acid Supplementation with Regular Deworming Is Cost-Effective in Preventing Anaemia in Women of Reproductive Age in Vietnam

    PubMed Central

    Horton, Susan E.; Phuc, Tran Q.; Phu, Luong B.; Thach, Dang T.; Dai, Tran C.; Fattore, Giovanni; Montresor, Antonio; Biggs, Beverley-A.

    2011-01-01

    Background To estimate the cost and cost-effectiveness of a project administering de-worming and weekly iron-folic acid supplementation to control anaemia in women of reproductive age in Yen Bai province, Vietnam. Methods and Findings Cost effectiveness was evaluated using data on programmatic costs based on two surveys in 2006 and 2009 and impact on anaemia and iron status collected in 2006, 2007, and 2008. Data on initial costs for training and educational materials were obtained from the records of the National Institute of Malariology, Parasitology and Entomology and the Yen Bai Malaria Control Program. Structured questionnaires for health workers at district, commune and village level were used to collect ongoing distribution and monitoring costs, and for participants to collect transport and loss of earnings costs. The cost per woman treated (defined as consuming at least 75% of the recommended intake) was USD0.76 per annum. This estimate includes financial costs (for supplies, training), and costs of health care workers' time. Prevalence of anaemia fell from 38% at baseline, to 20% after 12 months. Thus, the cost-effectiveness of the project is assessed at USD 4.24 per anaemia case prevented per year. Based on estimated productivity gains for adult women, the benefit:cost ratio is 6.7∶1. Cost of the supplements and anthelminthics was 47% of the total, while costs of training, monitoring, and health workers' time accounted for 53%. Conclusion The study shows that weekly iron-folic acid supplementation and regular de-worming is a low-cost and cost-effective intervention and would be appropriate for population-based introduction in settings with a high prevalence of anaemia and iron deficiency and low malaria infection rates. PMID:21931611

  11. Prevention of neural tube defects by the fortification of flour with folic acid: a population-based retrospective study in Brazil

    PubMed Central

    Lecca, Roberto Carlos Reyes; Cortez-Escalante, Juan Jose; Sanchez, Mauro Niskier; Rodrigues, Humberto Gabriel

    2016-01-01

    Abstract Objective To determine if the fortification of wheat and maize flours with iron and folic acid – which became mandatory in Brazil from June 2004 – is effective in the prevention of neural tube defects. Methods Using data from national information systems on births in central, south-eastern and southern Brazil, we determined the prevalence of neural tube defects among live births and stillbirths in a pre-fortification period – i.e. 2001–2004 – and in a post-fortification period – i.e. 2005–2014. We distinguished between anencephaly, encephalocele, meningocele, myelomeningocele and other forms of spina bifida. Findings There were 8554 neural tube defects for 17 925 729 live births notified between 2001 and 2014. For the same period, 2673 neural tube defects were reported for 194 858 stillbirths. The overall prevalence of neural tube defects fell from 0.79 per 1000 pre-fortification to 0.55 per 1000 post-fortification (prevalence ratio, PR: 1.43; 95% confidence interval, CI: 1.38–1.50). For stillbirths, prevalence fell from 17.74 per 1000 stillbirths pre-fortification to 11.70 per 1000 stillbirths post-fortification. The corresponding values among live births were 0.57 and 0.44, respectively. Conclusion The introduction of the mandatory fortification of flour with iron and folic acid in Brazil was followed by a significant reduction in the prevalence of neural tube defects in our study area. PMID:26769993

  12. Fabrication and spectroscopic studies of folic acid-conjugated Fe3O4@Au core-shell for targeted drug delivery application

    NASA Astrophysics Data System (ADS)

    Karamipour, Sh.; Sadjadi, M. S.; Farhadyar, N.

    2015-09-01

    Gold coated magnetite core shell is a kind of nanoparticle that include magnetic iron oxide core with a thin layer nanogold. Fe3O4-gold core-shell nanostructure can be used in biomedical applications such as magnetic bioseparation, bioimaging, targeting drug delivery and cancer treatment. In this study, the synthesis and characterization of gold coated magnetite nanoparticles were discussed. Magnetite nanoparticles with an average size of 6 nm in diameter were synthesized by the chemical co-precipitation method and gold-coated Fe3O4 core-shell nanostructures were produced with an average size of 11.5 nm in diameter by reduction of Au3+ with citrate ion in the presence of Fe3O4. Folate-conjugated gold coated magnetite nanoparticles were synthesized to targeting folate receptor that is overexpressed on the surface of cancerous cells. For this purpose, we used L-cysteine, as a bi-functional linker for attachment to gold surface and it was linked to the gold nanoparticles surface through its thiol group. Then, we conjugated amino-terminated nanoparticles to folic acid with an amide-linkage formation. These gold magnetic nanoparticles were characterized by various techniques such as X-ray powder diffraction (XRD) analysis, Fourier transform infrared spectrometer (FT-IR), UV-visible spectroscopy, transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), dispersive analysis of X-ray (EDAX) and vibrating sample magnetometer (VSM) analysis. The magnetic and optical properties of Fe3O4 nanostructure were changed by gold coating and attachment of L-cysteine and folic acid to Fe3O4@Au nanoparticles.

  13. Effect of vitamin B12 and folic acid supplementation on biomarkers of endothelial function and inflammation among elderly individuals with hyperhomocysteinemia.

    PubMed

    van Dijk, Suzanne C; Enneman, Anke W; Swart, Karin Ma; van Wijngaarden, Janneke P; Ham, Annelies C; de Jonge, R; Blom, Henk J; Feskens, Edith J; Geleijnse, Johanna Marianne; van Schoor, Natasja M; Dhonukshe-Rutten, Rosalie Am; de Jongh, Renate T; Lips, Paul; de Groot, Lisette Cpgm; Uitterlinden, Andre G; van den Meiracker, Ton H; Mattace-Raso, Francesco Us; van der Velde, Nathalie; Smulders, Yvo M

    2016-04-01

    B-vitamin trials failed to demonstrate beneficial effects on cardiovascular outcomes, but hyperhomocysteinemia still stands out as an independent cardiovascular risk factor, particularly in elderly individuals. B-vitamins may influence early vascular dysfunction, such as endothelial dysfunction, or may have adverse effects, for example on inflammation. We investigated the effect of B-vitamins on endothelial function and inflammation within an interventional study. This study was conducted within the framework of the B-PROOF trial, which included 2919 hyperhomocysteinemic elderly individuals, who received daily vitamin B12 (500 μg) and folic acid (400 μg) or placebo for 2 years. Using an electrochemiluminescence platform, we measured intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), serum amyloid A (SAA), vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) at baseline and follow-up in a subsample of 522 participants (271 intervention group; 251 placebo). Treatment effects were analyzed with ANCOVA. The participants had a mean age of 72 years, and 55% of them were male. At the 2-year follow-up, B-vitamins did not change the ICAM-1 (+36% change in the intervention group versus +32% change in the placebo group; p = 0.72), VCAM-1 (+27% vs +25%; p = 0.39), VEGF (-1% vs +4%; p = 0.40), SAA (+34% vs +38%; p = 0.85) or CRP levels (+26% vs +36%; p = 0.70) as compared to placebo. In conclusion, in elderly patients with hyperhomocysteinemia, vitamin B12 and folic acid are unlikely to influence either endothelial function or low-grade systemic inflammation. CLINICALTRIALSGOV IDENTIFIER NCT00696514. PMID:26774115

  14. A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis.

    PubMed

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

    2007-07-01

    Nationwide fortification of enriched uncooked cereal grains with folic acid began in the United States and Canada in 1996 and 1997, respectively, and became mandatory in 1998. The rationale was to reduce the number of births complicated by neural tube defects. Concurrently, the United States and Canada experienced abrupt reversals of the downward trend in colorectal cancer (CRC) incidence that the two countries had enjoyed in the preceding decade: absolute rates of CRC began to increase in 1996 (United States) and 1998 (Canada), peaked in 1998 (United States) and 2000 (Canada), and have continued to exceed the pre-1996/1997 trends by 4 to 6 additional cases per 100,000 individuals. In each country, the increase in CRC incidence from the prefortification trend falls significantly outside of the downward linear fit based on nonparametric 95% confidence intervals. The statistically significant increase in rates is also evident when the data for each country are analyzed separately for men and women. Changes in the rate of colorectal endoscopic procedures do not seem to account for this increase in CRC incidence. These observations alone do not prove causality but are consistent with the known effects of folate on existing neoplasms, as shown in both preclinical and clinical studies. We therefore hypothesize that the institution of folic acid fortification may have been wholly or partly responsible for the observed increase in CRC rates in the mid-1990s. Further work is needed to definitively establish the nature of this relationship. In the meantime, deliberations about the institution or enhancement of fortification programs should be undertaken with these considerations in mind. PMID:17626997

  15. Indole-3-acetic acid antagonists of the prostaglandin D2 receptor CRTH2.

    PubMed

    Armer, Richard E; Ashton, Mark R; Boyd, Edward A; Brennan, Chris J; Brookfield, Frederick A; Gazi, Lucien; Gyles, Shân L; Hay, Philip A; Hunter, Michael G; Middlemiss, David; Whittaker, Mark; Xue, Luzheng; Pettipher, Roy

    2005-10-01

    Prostaglandin D2 (PGD2) acting at the CRTH2 receptor (chemoattractant receptor-homologous molecule expressed on Th2 cells) has been linked with a variety of allergic and other inflammatory diseases. We describe a family of indole-1-sulfonyl-3-acetic acids that are potent and selective CRTH2 antagonists that possess good oral bioavailability. The compounds may serve as novel starting points for the development of treatments of inflammatory disease such as asthma, allergic rhinitis, and atopic dermatitis. PMID:16190744

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

    PubMed Central

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

    2010-01-01

    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. PMID:20802128

  17. In vitro competitive adhesion and production of antagonistic compounds by lactic acid bacteria against fish pathogens.

    PubMed

    Balcázar, José Luis; Vendrell, Daniel; de Blas, Ignacio; Ruiz-Zarzuela, Imanol; Gironés, Olivia; Múzquiz, José Luis

    2007-06-21

    The present study describes the screening of five lactic acid bacteria (LAB) for use as probiotics based on their competitive adhesion and production of antagonistic substances against some fish pathogens. A reduction of adhesion of all pathogenic strains tested was obtained with three of the LAB strains (Lactococcus lactis subsp. lactis CLFP100, Lactococcus lactis subsp. cremoris CLFP102 and Lactobacillus curvatus CLFP150). With the exception of fish pathogens Flavobacterium psychrophilum and Renibacterium salmoninarum that were not inhibited by LAB strains, production of antagonistic compounds by all tested LAB was observed against at least one of the indicator strains. Based on mucus adhesion, competitive exclusion, and suppression of fish pathogen growth, the selected LAB strains can be considered for future challenge experiments in fish as a very promising alternative to the use of chemotherapeutic agents. PMID:17336468

  18. Transcriptomic insights into antagonistic effects of gibberellin and abscisic acid on petal growth in Gerbera hybrida

    PubMed Central

    Li, Lingfei; Zhang, Wenbin; Zhang, Lili; Li, Na; Peng, Jianzong; Wang, Yaqin; Zhong, Chunmei; Yang, Yuping; Sun, Shulan; Liang, Shan; Wang, Xiaojing

    2015-01-01

    Petal growth is central to floral morphogenesis, but the underlying genetic basis of petal growth regulation is yet to be elucidated. In this study, we found that the basal region of the ray floret petals of Gerbera hybrida was the most sensitive to treatment with the phytohormones gibberellin (GA) and abscisic acid (ABA), which regulate cell expansion during petal growth in an antagonistic manner. To screen for differentially expressed genes (DEGs) and key regulators with potentially important roles in petal growth regulation by GA or/and ABA, the RNA-seq technique was employed. Differences in global transcription in petals were observed in response to GA and ABA and target genes antagonistically regulated by the two hormones were identified. Moreover, we also identified the pathways associated with the regulation of petal growth after application of either GA or ABA. Genes relating to the antagonistic GA and ABA regulation of petal growth showed distinct patterns, with genes encoding transcription factors (TFs) being active during the early stage (2 h) of treatment, while genes from the apoptosis and cell wall organization categories were expressed at later stages (12 h). In summary, we present the first study of global expression patterns of hormone-regulated transcripts in G. hybrida petals; this dataset will be instrumental in revealing the genetic networks that govern petal morphogenesis and provides a new theoretical basis and novel gene resources for ornamental plant breeding. PMID:25852718

  19. Transcriptomic insights into antagonistic effects of gibberellin and abscisic acid on petal growth in Gerbera hybrida.

    PubMed

    Li, Lingfei; Zhang, Wenbin; Zhang, Lili; Li, Na; Peng, Jianzong; Wang, Yaqin; Zhong, Chunmei; Yang, Yuping; Sun, Shulan; Liang, Shan; Wang, Xiaojing

    2015-01-01

    Petal growth is central to floral morphogenesis, but the underlying genetic basis of petal growth regulation is yet to be elucidated. In this study, we found that the basal region of the ray floret petals of Gerbera hybrida was the most sensitive to treatment with the phytohormones gibberellin (GA) and abscisic acid (ABA), which regulate cell expansion during petal growth in an antagonistic manner. To screen for differentially expressed genes (DEGs) and key regulators with potentially important roles in petal growth regulation by GA or/and ABA, the RNA-seq technique was employed. Differences in global transcription in petals were observed in response to GA and ABA and target genes antagonistically regulated by the two hormones were identified. Moreover, we also identified the pathways associated with the regulation of petal growth after application of either GA or ABA. Genes relating to the antagonistic GA and ABA regulation of petal growth showed distinct patterns, with genes encoding transcription factors (TFs) being active during the early stage (2 h) of treatment, while genes from the "apoptosis" and "cell wall organization" categories were expressed at later stages (12 h). In summary, we present the first study of global expression patterns of hormone-regulated transcripts in G. hybrida petals; this dataset will be instrumental in revealing the genetic networks that govern petal morphogenesis and provides a new theoretical basis and novel gene resources for ornamental plant breeding. PMID:25852718

  20. Effects of gamma-aminobutyric acid agonist and antagonist drugs on local cerebral glucose utilization

    SciTech Connect

    Palacios, J.M.; Kuhar, M.J.; Rapoport, S.I.; London, E.D.

    1982-07-01

    The (/sup 14/C)2-deoxy-D-glucose method of Sokoloff et al. was used to study local cerebral glucose utilization (LCGU) in rats treated with gamma-aminobutyric acid (GABA) agonist (muscimol and 4,5,6,7-tetrahydroisoxazolo(5,4-C)pyridin-3-ol, THIP) and antagonist (bicuculline) drugs. It was of interest to determine if the pattern of LCGU responses to GABA agonists and antagonists administered systemically in vivo would reflect the known distributions of markers for central GABAergic synapses. The patterns of LCGU responses to muscimol and THIP generally were similar. Most brain regions showed dose-dependent decreases in LCGU; others showed no effects; but the red nucleus showed an increase. The GABA antagonist bicuculline produced convulsions and variable LCGU responses, depending on the time of administration. Bicuculline also partially antagonized the depressant effects of muscimol of LCGU. The magnitudes and distribution of in vivo cerebral metabolic responses to specific GABA agonists were not correlated simply with markers for GABAergic synapses. This lack of correlation indicates that additional factors, such as neural circuitry, regulate the LCGU responses to GABAergic drugs.

  1. Effects of the putative antagonists phaclofen and delta-aminovaleric acid on GABAB receptor biochemistry.

    PubMed Central

    Robinson, T. N.; Cross, A. J.; Green, A. R.; Toczek, J. M.; Boar, B. R.

    1989-01-01

    1. Phaclofen and delta-aminovaleric acid (delta-AVA) have been reported to be antagonists at gamma-aminobutyric acidB (GABAB) receptors. Phaclofen, delta-AVA and related compounds were examined for potency and specificity at GABAB and GABAA receptors in rat cortical membranes labelled with [3H]-(-)-baclofen and [3H]-muscimol, respectively. Additionally phaclofen and delta-AVA were examined in two functional tests of central GABAB activity in rat cortical slices, namely the inhibition of forskolin-stimulated cyclic AMP accumulation, and the potentiation of isoprenaline-stimulated cyclic AMP accumulation. 2. delta-AVA (IC50 = 11.7 microM) was 20 fold more potent than phaclofen (IC50 = 229 microM) on GABAB receptor binding. All compounds possessing a phosphonic acid group, including phaclofen, which were active at GABAB receptors were inactive at GABAA receptors, while delta-AVA was equally potent at both receptors. Several compounds exhibited Hill coefficients of less than unity in displacing [3H]-(-)-baclofen binding. 3. (-)-Baclofen inhibited forskolin-stimulated cyclic AMP accumulation (IC50 = 7.9 microM) but this effect was not stereospecific. Phaclofen (1 mM) was inactive against this inhibition but produced a potentiation of the forskolin effect. delta-AVA (1 mM) failed to antagonize the effect of baclofen; rather it mimicked baclofen. 4. (-)-Baclofen (10 microM) potentiated isoprenaline-stimulated cyclic AMP accumulation, an effect antagonized by phaclofen (1 mM). delta-AVA (1 mM) may be a weak antagonist but also potentiated basal cyclic AMP accumulation. 5. We conclude that neither delta-AVA nor phaclofen are potent specific GABAB receptor antagonists. PMID:2556202

  2. Identification of Darmstoff analogs as selective agonists and antagonists of lysophosphatidic acid receptors.

    PubMed

    Gududuru, Veeresa; Zeng, Kui; Tsukahara, Ryoko; Makarova, Natalia; Fujiwara, Yuko; Pigg, Kathryn R; Baker, Daniel L; Tigyi, Gabor; Miller, Duane D

    2006-01-15

    Darmstoff describes a family of gut smooth muscle-stimulating acetal phosphatidic acids initially isolated and characterized from the bath fluid of stimulated gut over 50 years ago. Despite similar structural and biological profiles, Darmstoff analogs have not previously been examined as potential LPA mimetics. Here, we report a facile method for the synthesis of potassium salts of Darmstoff analogs. To understand the effect of stereochemistry on lysophosphatidic acid mimetic activity, synthesis of optically pure stereoisomers of selected Darmstoff analogs was achieved starting with chiral methyl glycerates. Each Darmstoff analog was evaluated for subtype-specific LPA receptor agonist/antagonist activity, PPARgamma activation, and autotaxin inhibition. From this study we identified compound 12 as a pan-antagonist and several pan-agonists for the LPA(1-3) receptors. Introduction of an aromatic ring in the lipid chain such as analog 22 produced a subtype-specific LPA(3) agonist with an EC(50) of 692 nM. Interestingly, regardless of their LPA(1/2/3) ligand properties all of the Darmstoff analogs tested activated PPARgamma. However, these compounds are weak inhibitors of autotaxin. The results indicate that Darmstoff analogs constitute a novel class of lysophosphatidic acid mimetics. PMID:16290140

  3. Bipiperidinyl carboxylic acid amides as potent, selective, and functionally active CCR4 antagonists.

    PubMed

    Kuhn, Cyrille F; Bazin, Marc; Philippe, Laurence; Zhang, Jiansu; Tylaska, Laurie; Miret, Juan; Bauer, Paul H

    2007-09-01

    A cell-based assay for the chemokine G-protein-coupled receptor CCR4 was developed, and used to screen a small-molecule compound collection in a multiplex format. A series of bipiperidinyl carboxylic acid amides amenable to parallel chemistry were derived that were potent and selective antagonists of CCR4. One prototype compound was shown to be active in a functional model of chemotaxis, making it a useful chemical tool to explore the role of CCR4 in asthma, allergy, diabetes, and cancer. PMID:17718722

  4. Adequately Diversified Dietary Intake and Iron and Folic Acid Supplementation during Pregnancy Is Associated with Reduced Occurrence of Symptoms Suggestive of Pre-Eclampsia or Eclampsia in Indian Women

    PubMed Central

    Agrawal, Sutapa; Fledderjohann, Jasmine; Vellakkal, Sukumar; Stuckler, David

    2015-01-01

    Background/Objective Pre-eclampsia or Eclampsia (PE or E) accounts for 25% of cases of maternal mortality worldwide. There is some evidence of a link to dietary factors, but few studies have explored this association in developing countries, where the majority of the burden falls. We examined the association between adequately diversified dietary intake, iron and folic acid supplementation during pregnancy and symptoms suggestive of PE or E in Indian women. Methods Cross-sectional data from India’s third National Family Health Survey (NFHS-3, 2005-06) was used for this study. Self-reported symptoms suggestive of PE or E during pregnancy were obtained from 39,657 women aged 15-49 years who had had a live birth in the five years preceding the survey. Multivariable logistic regression analysis was used to estimate the association between adequately diversified dietary intake, iron and folic acid supplementation during pregnancy and symptoms suggestive of PE or E after adjusting for maternal, health and lifestyle factors, and socio-demographic characteristics of the mother. Results In their most recent pregnancy, 1.2% (n=456) of the study sample experienced symptoms suggestive of PE or E. Mothers who consumed an adequately diversified diet were 34% less likely (OR: 0.66; 95% CI: 0.51-0.87) to report PE or E symptoms than mothers with inadequately diversified dietary intake. The likelihood of reporting PE or E symptoms was also 36% lower (OR: 0.64; 95% CI: 0.47-0.88) among those mothers who consumed iron and folic acid supplementation for at least 90 days during their last pregnancy. As a sensitivity analysis, we stratified our models sequentially by education, wealth, antenatal care visits, birth interval, and parity. Our results remained largely unchanged: both adequately diversified dietary intake and iron and folic acid supplementation during pregnancy were associated with a reduced occurrence of PE or E symptoms. Conclusion Having a adequately diversified dietary intake and iron and folic acid supplementation in pregnancy was associated with a reduced occurrence of symptoms suggestive of PE or E in Indian women. PMID:25785774

  5. Determinants of neural tube defect (NTD)-protective circulating concentrations of folate in women of child-bearing age in the US post-folic acid fortification era.

    PubMed

    Piyathilake, Chandrika; Eom, Sang Yong; Hyun, Taisun; Badiga, Suguna; Robinson, Constance; Rahman, Nuzhat; Kim, Heon; Johanning, Gary L

    2013-08-01

    We evaluated folate status of child-bearing age women diagnosed with abnormal pap smear in the US post-folic acid (FA) fortification era and assessed the determinants of NTD-protective and supra-physiologic (SP) concentrations of folate. The distribution of 843 women according to NTD-protective concentrations of RBC folate, plasma folate and SP concentrations of plasma folate were tested in relation to demographic and life-style factors. Logistic regression models specified NTD-protective concentrations of RBC and plasma folate or SP concentrations of plasma folate as dependent variables and demographic and life-style factors as independent predictors of interest. More than 82% reached NTD-protective concentrations of RBC and plasma folate and ~30% reached SP concentrations of plasma folate. FA supplement use was associated with having SP concentrations of plasma folate rather than NTD-protective concentrations of folate. African American (AA) women and smokers were significantly less likely to achieve NTD-protective concentrations of RBC and plasma folate. A large majority of women reached NTD-protective concentrations of folate with the current level of FA fortification without using supplementary FA. Therefore, the remaining disparities in AA women and in smokers should be addressed by targeted individual improvements in folate intake. PMID:23964320

  6. Determinants of neural tube defect (NTD)-protective circulating concentrations of folate in women of child-bearing age in the US post-folic acid fortification era

    PubMed Central

    Eom, Sang Yong; Hyun, Taisun; Badiga, Suguna; Robinson, Constance; Rahman, Nuzhat; Kim, Heon; Johanning, Gary L

    2013-01-01

    We evaluated folate status of child-bearing age women diagnosed with abnormal pap smear in the US post-folic acid (FA) fortification era and assessed the determinants of NTD-protective and supra-physiologic (SP) concentrations of folate. The distribution of 843 women according to NTD-protective concentrations of RBC folate, plasma folate and SP concentrations of plasma folate were tested in relation to demographic and life-style factors. Logistic regression models specified NTD-protective concentrations of RBC and plasma folate or SP concentrations of plasma folate as dependent variables and demographic and life-style factors as independent predictors of interest. More than 82% reached NTD-protective concentrations of RBC and plasma folate and ~30% reached SP concentrations of plasma folate. FA supplement use was associated with having SP concentrations of plasma folate rather than NTD-protective concentrations of folate. African American (AA) women and smokers were significantly less likely to achieve NTD-protective concentrations of RBC and plasma folate. A large majority of women reached NTD-protective concentrations of folate with the current level of FA fortification without using supplementary FA. Therefore, the remaining disparities in AA women and in smokers should be addressed by targeted individual improvements in folate intake. PMID:23964320

  7. A folic acid labelled carbon quantum dot-protoporphryin IX conjugate for use in folate receptor targeted two-photon excited photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Nicholas, Dean; Fowley, Colin; McHale, Anthony P.; Kamila, Sukanta; Sheng, Jason; Atchison, Jordan; Callan, John F.

    2015-03-01

    Folic acid (FA) has been used as a molecular targeting strategy to improve the specificity of a CQD-protoporphyrin IX (CQD-PPIX) conjugate to folate receptor positive (FR+) HeLa cells for use in two-photon excited Photodynamic Therapy (TPE-PDT). FA was covalently attached to the CQD-PPIX conjugate to form a FA-CQD-PPIX conjugate. The uptake of the FA-CQD-PPIX conjugate in FR+ HeLa cells was shown to be 7 times greater than the CQD-PPIX conjugate, while both conjugates showed a similar uptake in FR negative (FR-) HT-47 cells. TPE-PDT experiments, using HeLa cells as a target, revealed a 30% improved cytotoxicity for cells treated with the FA-CQD-PPIX conjugate and TPE compared to controls treated with the CQD-PPIX conjugate and TPE. Collectively, these results suggest the presence of FA can facilitate targeting of CQD-sensitiser conjugates to FR+ cells resulting in an improved PDT effect.

  8. Recoupling of eNOS with Folic Acid Prevents Abdominal Aortic Aneurysm Formation in Angiotensin II-Infused Apolipoprotein E Null Mice

    PubMed Central

    Siu, Kin Lung; Miao, Xiao Niu; Cai, Hua

    2014-01-01

    We have previously shown that eNOS uncoupling mediates abdominal aortic aneurysm (AAA) formation in hph-1 mice. In the present study we examined whether recoupling of eNOS prevents AAA formation in a well-established model of Angiotensin II-infused apolipoprotein E (apoE) null mice by targeting some common pathologies of AAA. Infusion of Ang II resulted in a 92% incidence rate of AAA in the apoE null animals. In a separate group, animals were treated orally with folic acid (FA), which is known to recouple eNOS through augmentation of dihydrofolate reductase (DHFR) function. This resulted in a reduction of AAA rate to 19.5%. Imaging with ultrasound showed that FA markedly inhibited expansion of abdominal aorta. FA also abolished elastin breakdown and macrophage infiltration in the AAA animals. The eNOS uncoupling activity, assessed by L-NAME-sensitive superoxide production, was minimal at baseline but greatly exaggerated with Ang II infusion, which was completely attenuated by FA. This was accompanied by markedly improved tetrahydrobiopterin and nitric oxide bioavailability. Furthermore, the expression and activity of DHFR was decreased in Ang II-infused apoE null mice specifically in the endothelial cells, while FA administration resulted in its recovery. Taken together, these data further establish a significant role of uncoupled eNOS in mediating AAA formation, and a universal efficacy of FA in preventing AAA formation via restoration of DHFR to restore eNOS function. PMID:24558445

  9. Iron-Folic Acid Supplementation During Pregnancy Reduces the Risk of Stunting in Children Less Than 2 Years of Age: A Retrospective Cohort Study from Nepal.

    PubMed

    Nisar, Yasir Bin; Dibley, Michael J; Aguayo, Victor M

    2016-01-01

    The aim of the study was to investigate the effect of antenatal iron-folic acid (IFA) supplementation on child stunting in Nepalese children age <2 years. A retrospective cohort study design was used, in which a pooled cohort of 5235 most recent live births 2 years prior to interview from three Nepal Demographic and Health Surveys (2001, 2006 and 2011) was analysed. The primary outcome was stunting in children age <2 years. The main exposure variable was antenatal IFA supplementation. Multivariate Poisson regression analysis was performed. In our sample, 31% and 10% of Nepalese children age <2 years were stunted and severely stunted, respectively. The adjusted relative risk of being stunted was 14% lower in children whose mothers used IFA supplements compared to those whose mothers did not use (aRR = 0.86, 95% CI = 0.77-0.97). Additionally, the adjusted relative risk of being stunted was significantly reduced by 23% when antenatal IFA supplementation was started ≤6 months with ≥90 IFA supplements used during pregnancy (aRR = 0.77, 95% CI = 0.64-0.92). Antenatal IFA supplementation significantly reduced the risk of stunting in Nepalese children age <2 years. The greatest impact on the risk reduction of child stunting was when IFA supplements were started ≤6 months with ≥90 supplements were used. PMID:26828515

  10. Polyethylenimine-capped silver nanoclusters as a fluorescence probe for highly sensitive detection of folic acid through a two-step electron-transfer process.

    PubMed

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

    2014-07-16

    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 μM. 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

  11. Fetal neural tube stem cells from Pax3 mutant mice proliferate, differentiate, and form synaptic connections when stimulated with folic acid.

    PubMed

    Ichi, Shunsuke; Nakazaki, Hiromichi; Boshnjaku, Vanda; Singh, Ravneet Monny; Mania-Farnell, Barbara; Xi, Guifa; McLone, David G; Tomita, Tadanori; Mayanil, Chandra Shekhar K

    2012-01-20

    Although maternal intake of folic acid (FA) prevents neural tube defects in 70% of the population, the exact mechanism of prevention has not been elucidated. We hypothesized that FA affects neural stem cell (NSC) proliferation and differentiation. This hypothesis was examined in a folate-responsive spina bifida mouse model, Splotch (Sp(-/-)), which has a homozygous loss-of-function mutation in the Pax3 gene. Neurospheres were generated with NSCs from the lower lumbar neural tube of E10.5 wild-type (WT) and Sp(-/-) embryos, in the presence and absence of FA. In the absence of FA, the number of neurospheres generated from Sp(-/-) embryos compared with WT was minimal (P<0.05). Addition of FA to Sp(-/-) cultures increased the expression of a Pax3 downstream target, fgfr4, and rescued NSC proliferative potential, as demonstrated by a significant increase in neurosphere formation (P<0.01). To ascertain if FA affected cell differentiation, FA-stimulated Sp(-/-) neurospheres were allowed to differentiate in the continued presence or absence of FA. Neurospheres from both conditions expressed multi-potent stem cell characteristics and the same differentiation potential as WT. Further, multiple neurospheres from both WT and FA-stimulated Sp(-/-) cell cultures formed extensive synaptic connections. On the whole, FA-mediated rescue of neural tube defects in Sp(-/-) embryos promotes NSC proliferation at an early embryonic stage. FA-stimulated Sp(-/-) neurospheres differentiate and form synaptic connections, comparable to WT. PMID:21521032

  12. Iron-Folic Acid Supplementation During Pregnancy Reduces the Risk of Stunting in Children Less Than 2 Years of Age: A Retrospective Cohort Study from Nepal

    PubMed Central

    Nisar, Yasir Bin; Dibley, Michael J.; Aguayo, Victor M.

    2016-01-01

    The aim of the study was to investigate the effect of antenatal iron-folic acid (IFA) supplementation on child stunting in Nepalese children age <2 years. A retrospective cohort study design was used, in which a pooled cohort of 5235 most recent live births 2 years prior to interview from three Nepal Demographic and Health Surveys (2001, 2006 and 2011) was analysed. The primary outcome was stunting in children age <2 years. The main exposure variable was antenatal IFA supplementation. Multivariate Poisson regression analysis was performed. In our sample, 31% and 10% of Nepalese children age <2 years were stunted and severely stunted, respectively. The adjusted relative risk of being stunted was 14% lower in children whose mothers used IFA supplements compared to those whose mothers did not use (aRR = 0.86, 95% CI = 0.77–0.97). Additionally, the adjusted relative risk of being stunted was significantly reduced by 23% when antenatal IFA supplementation was started ≤6 months with ≥90 IFA supplements used during pregnancy (aRR = 0.77, 95% CI = 0.64–0.92). Antenatal IFA supplementation significantly reduced the risk of stunting in Nepalese children age <2 years. The greatest impact on the risk reduction of child stunting was when IFA supplements were started ≤6 months with ≥90 supplements were used. PMID:26828515

  13. Microarray Analysis Reveals Higher Gestational Folic Acid Alters Expression of Genes in the Cerebellum of Mice Offspring—A Pilot Study

    PubMed Central

    Barua, Subit; Kuizon, Salomon; Chadman, Kathryn K.; Brown, W. Ted; Junaid, Mohammed A.

    2015-01-01

    Folate is a water-soluble vitamin that is critical for nucleotide synthesis and can modulate methylation of DNA by altering one-carbon metabolism. Previous studies have shown that folate status during pregnancy is associated with various congenital defects including the risk of aberrant neural tube closure. Maternal exposure to a methyl supplemented diet also can alter DNA methylation and gene expression, which may influence the phenotype of offspring. We investigated if higher gestational folic acid (FA) in the diet dysregulates the expression of genes in the cerebellum of offspring in C57BL/6 J mice. One week before gestation and throughout the pregnancy, groups of dams were supplemented with FA either at 2 mg/kg or 20 mg/kg of diet. Microarray analysis was used to investigate the genome wide gene expression profile in the cerebellum from day old pups. Our results revealed that exposure to the higher dose FA diet during gestation dysregulated expression of several genes in the cerebellum of both male and female pups. Several transcription factors, imprinted genes, neuro-developmental genes and genes associated with autism spectrum disorder exhibited altered expression levels. These findings suggest that higher gestational FA potentially dysregulates gene expression in the offspring brain and such changes may adversely alter fetal programming and overall brain development. PMID:25629700

  14. Effect of Folic Acid, Betaine, Vitamin B6, and Vitamin B12 on Homocysteine and Dimethylglycine Levels in Middle-Aged Men Drinking White Wine

    PubMed Central

    Rajdl, Daniel; Racek, Jaroslav; Trefil, Ladislav; Stehlik, Pavel; Dobra, Jana; Babuska, Vaclav

    2016-01-01

    Moderate regular consumption of alcoholic beverages is believed to protect against atherosclerosis but can also increase homocysteine or dimethylglycine, which are putative risk factors for atherosclerosis. We aimed (1) to investigate the effect of alcohol consumption on vitamins and several metabolites involved in one-carbon metabolism; and (2) to find the most effective way of decreasing homocysteine during moderate alcohol consumption. Methods: Male volunteers (n = 117) were randomly divided into five groups: the wine-only group (control, 375 mL of white wine daily for one month) and four groups combining wine consumption with one of the supplemented substances (folic acid, betaine, and vitamins B12 or B6). Significant lowering of homocysteine concentration after the drinking period was found in subjects with concurrent folate and betaine supplementation. Vitamin B12 and vitamin B6 supplementation did not lead to a statistically significant change in homocysteine. According to a multiple linear regression model, the homocysteine change in the wine-only group was mainly determined by the interaction between the higher baseline homocysteine concentration and the change in dimethylglycine levels. Folate and betaine can attenuate possible adverse effects of moderate alcohol consumption. Dimethylglycine should be interpreted together with data on alcohol consumption and homocysteine concentration. PMID:26771632

  15. Reduced folate and serum vitamin metabolites in patients with rectal carcinoma: an open-label feasibility study of pemetrexed with folic acid and vitamin B12 supplementation.

    PubMed

    Stoffregen, Clemens C; Odin, Elisabeth A; Carlsson, Göran U; Kurlberg, Göran K; Björkqvist, Hillevi G; Tångefjord, Maria T; Gustavsson, Bengt G

    2016-06-01

    The objectives of this single-center, open-label, phase II study were to evaluate (a) the feasibility and safety of neoadjuvant administration of pemetrexed with oral folic acid and vitamin B12 (FA/B12) in newly diagnosed patients with resectable rectal cancer and (b) intracellular and systemic vitamin metabolism. Patients were treated with three cycles of pemetrexed (500 mg/m, every 3 weeks) and FA/B12 before surgery. The reduced folates tetrahydrofolate, 5-methyltetrahydrofolate, and 5,10-methylenetetrahydrofolate were evaluated from biopsies in tumor tissue and in adjacent mucosa. Serum levels of homocysteine, cystathionine, and methylmalonic acid were also measured. All 37 patients received three cycles of pemetrexed; 89.2% completed their planned dosage within a 9-week feasibility time frame. Neither dose reductions nor study drug-related serious adverse events were reported. Reduced folate levels were significantly higher in tumor tissue compared with adjacent mucosa at baseline. After FA/B12 administration, tissue levels of reduced folates increased significantly and remained high during treatment in both tumor and mucosa until surgery. Serum levels of cystathionine increased significantly compared with baseline after FA/B12 administration, but then decreased, fluctuating cyclically during pemetrexed therapy. Homocysteine and methylmalonic acid levels decreased significantly after FA/B12 administration, and remained below baseline levels during the study. These results indicate that administration of three neoadjuvant cycles of single-agent pemetrexed, every 3 weeks, with FA/B12 in patients with resectable rectal cancer is feasible and tolerable. Tissue and serum vitamin metabolism results demonstrate the influence of pemetrexed and FA/B12 on vitamin metabolism and warrant further study. PMID:26825869

  16. Reduced folate and serum vitamin metabolites in patients with rectal carcinoma: an open-label feasibility study of pemetrexed with folic acid and vitamin B12 supplementation

    PubMed Central

    Odin, Elisabeth A.; Carlsson, Göran U.; Kurlberg, Göran K.; Björkqvist, Hillevi G.; Tångefjord, Maria T.; Gustavsson, Bengt G.

    2016-01-01

    The objectives of this single-center, open-label, phase II study were to evaluate (a) the feasibility and safety of neoadjuvant administration of pemetrexed with oral folic acid and vitamin B12 (FA/B12) in newly diagnosed patients with resectable rectal cancer and (b) intracellular and systemic vitamin metabolism. Patients were treated with three cycles of pemetrexed (500 mg/m2, every 3 weeks) and FA/B12 before surgery. The reduced folates tetrahydrofolate, 5-methyltetrahydrofolate, and 5,10-methylenetetrahydrofolate were evaluated from biopsies in tumor tissue and in adjacent mucosa. Serum levels of homocysteine, cystathionine, and methylmalonic acid were also measured. All 37 patients received three cycles of pemetrexed; 89.2% completed their planned dosage within a 9-week feasibility time frame. Neither dose reductions nor study drug-related serious adverse events were reported. Reduced folate levels were significantly higher in tumor tissue compared with adjacent mucosa at baseline. After FA/B12 administration, tissue levels of reduced folates increased significantly and remained high during treatment in both tumor and mucosa until surgery. Serum levels of cystathionine increased significantly compared with baseline after FA/B12 administration, but then decreased, fluctuating cyclically during pemetrexed therapy. Homocysteine and methylmalonic acid levels decreased significantly after FA/B12 administration, and remained below baseline levels during the study. These results indicate that administration of three neoadjuvant cycles of single-agent pemetrexed, every 3 weeks, with FA/B12 in patients with resectable rectal cancer is feasible and tolerable. Tissue and serum vitamin metabolism results demonstrate the influence of pemetrexed and FA/B12 on vitamin metabolism and warrant further study. PMID:26825869

  17. Homocysteine homeostasis in the rat is maintained by compensatory changes in cystathionine ?-synthase, betaine-homocysteine methyltransferase, and phosphatidylethanolamine N-methyltransferase gene transcription occurring in response to maternal protein and folic acid intake during pregnancy and fat intake after weaning.

    PubMed

    Chmurzynska, Agata; Malinowska, Anna M

    2011-07-01

    The reactions of the methionine/homocysteine pathway are mediated by several enzymes, including phosphatidylethanolamine N-methyltransferase, cystathionine ?-synthase, and betaine-homocysteine methyltransferase. Homocysteine homeostasis is regulated by these enzymes. We hypothesized here that the protein and folic acid content in the maternal diet affects methionine/homocysteine metabolism in the progeny. To test this hypothesis, pregnant rats were fed a diet with normal protein and normal folic acid levels (a modified casein-based AIN-93G diet), a protein-restricted and normal folic acid diet, a protein-restricted and folic acid-supplemented diet, or a normal protein and folic acid-supplemented diet. The progeny were fed either the modified AIN-93G diet or a high-fat lard-based diet. Progeny were analyzed for expression of the phosphatidylethanolamine N-methyltransferase, cystathionine ?-synthase, and betaine-homocysteine methyltransferase genes in the liver and for serum homocysteine concentration. Interactions between prenatal and postnatal nutrition were also determined. The progeny of the dams fed the diets supplemented with folic acid showed decreased expression of all 3 genes (P < .001). An interaction effect between the protein and folic acid content in the maternal diet contributed to this down-regulation (P < .001), and the postweaning diet modified these effects. Serum homocysteine concentrations were approximately 15% higher in the male rats (P < .01), but neither prenatal nutrition nor the postweaning diet affected it significantly. We conclude that maternal diet during gestation has an important effect on the transcription level of these 3 genes, but changes in gene expression were not associated with significant changes in progeny homocysteine concentrations. PMID:21840474

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

    PubMed

    Maeda, Yasuo; Mayanagi, Taira; Amagai, Aiko

    2009-03-01

    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

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

    SciTech Connect

    Bhandari, Deepak; Kertesz, Vilmos; Van Berkel, Gary J

    2013-01-01

    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.

  20. A Functionalized Congener Approach to Adenosine Receptor Antagonists: Amino Acid Conjugates of 1,3-Dipropylxanthine

    PubMed Central

    JACOBSON, KENNETH A.; KIRK, KENNETH L.; PADGETT, WILLIAM L.; DALY, JOHN W.

    2012-01-01

    SUMMARY 1,3-Dipropyl-8-phenylxanthine, a synthetic analog of theophylline and a potent antagonist of adenosine at A1 and A2-adenosine receptors, has been attached covalently through a functionalized chain to amino acids and oligopeptides. The xanthine conjugates have been studied as competitive inhibitors of the specific binding of [3H]N6-cyclohexyladenosine to A1-receptors of rat cerebral cortical membranes and for inhibition of cyclic AMP accumulation elicited by 2-chloroadenosine in guinea pig brain slices through A2-receptors. A free amino group on the extended chain generally resulted in high potency at A1-receptors. The potency (in some cases extending into the subnanomolar range) and selectivity for A1-receptors (up to 200-fold) suggest that this approach can yield a versatile class of “functionalized congeners” of adenosine receptor antagonists in which distal modifications of the attached moiety (“carrier”) can serve also to improve pharmacodynamic and pharmacokinetic parameters. The water solubility in many of the more potent analogs has been enhanced by two orders of magnitude over that of simple, uncharged 8-phenyl xanthine derivatives. Analogs in which the carrier contains d-tyrosine have potential for development of iodinated radioligands for adenosine receptors. The functionalized congener approach is potentially applicable to other drugs and for development of prodrugs. PMID:3005825

  1. Interactions between plasma concentrations of folate and markers of vitamin B(12) status with cognitive performance in elderly people not exposed to folic acid fortification: the Hordaland Health Study.

    PubMed

    Doets, Esmée L; Ueland, Per M; Tell, Grethe S; Vollset, Stein Emil; Nygård, Ottar K; Van't Veer, Pieter; de Groot, Lisette C P G M; Nurk, Eha; Refsum, Helga; Smith, A David; Eussen, Simone J P M

    2014-03-28

    A combination of high folate with low vitamin B12 plasma status has been associated with cognitive impairment in a population exposed to mandatory folic acid fortification. The objective of the present study was to examine the interactions between plasma concentrations of folate and vitamin B12 markers in relation to cognitive performance in Norwegian elderly who were unexposed to mandatory or voluntary folic acid fortification. Cognitive performance was assessed by six cognitive tests in 2203 individuals aged 72-74 years. A combined score was calculated using principal component analysis. The associations of folate concentrations, vitamin B12 markers (total vitamin B12, holotranscobalamin (holoTC) and methylmalonic acid (MMA)) and their interactions in relation to cognitive performance were evaluated by quantile regression and least-squares regression, adjusted for sex, education, apo-ɛ4 genotype, history of CVD/hypertension and creatinine. Cross-sectional analyses revealed an interaction (P= 0·009) between plasma concentrations of folate and vitamin B12 in relation to cognitive performance. Plasma vitamin B12 concentrations in the lowest quartile ( < 274 pmol/l) combined with plasma folate concentrations in the highest quartile (>18·5 nmol/l) were associated with a reduced risk of cognitive impairment compared with plasma concentrations in the middle quartiles of both vitamins (OR 0·22, 95 % CI 0·05, 0·92). The interaction between folate and holoTC or MMA in relation to cognitive performance was not significant. In conclusion, this large study population unexposed to mandatory folic acid fortification showed that plasma folate, but not plasma vitamin B12, was associated with cognitive performance. Among the elderly participants with vitamin B12 concentrations in the lower range, the association between plasma folate and cognitive performance was strongest. PMID:24229560

  2. In vivo targeted magnetic resonance imaging and visualized photodynamic therapy in deep-tissue cancers using folic acid-functionalized superparamagnetic-upconversion nanocomposites

    NASA Astrophysics Data System (ADS)

    Zeng, Leyong; Luo, Lijia; Pan, Yuanwei; Luo, Song; Lu, Guangming; Wu, Aiguo

    2015-05-01

    Multifunctional nanoprobes used in magnetic resonance imaging (MRI) and photodynamic therapy (PDT) also have potential applications in diagnosis and visualized therapy of cancers, and hence it is important to investigate the active-targeting ability and in vivo reliability of these nanoprobes. In this work, folic acid (FA)-targeted, photosensitizer (PS)-loaded Fe3O4@NaYF4:Yb/Er (FA-NPs-PS) nanocomposites were synthesized for in vivo T2-weighted MRI and visualized PDT of cancers by modeling MCF-7 tumor-bearing nude mice. By measuring the upconversion luminescence (UCL) and fluorescence emission spectra, the as-prepared FA-NPs-PS nanocomposites showed near-infrared (NIR)-triggered PDT performance due to the production of a singlet oxygen species. Moreover, by tracing PS fluorescence in MCF-7, HeLa cells and in MCF-7 tumors, the FA-targeted nanocomposites demonstrated good targeting ability both in vitro and in vivo. Under the irradiation of a 980 nm laser, the viabilities of MCF-7 and HeLa cells incubated with FA-NPs-PS nanocomposites could decrease to about 18.4% and 30.7%, respectively, and the inhibition of MCF-7 tumors could reach about 94.9%. The transverse MR relaxivity of 63.79 mM-1 s-1 (r2 value) and in vivo MR imaging of MCF-7 tumors indicated an excellent T2-weighted MR performance. This work demonstrated that FA-targeted MRI/PDT nanoprobes are effective for in vivo diagnosis and visualized therapy of breast cancers.Multifunctional nanoprobes used in magnetic resonance imaging (MRI) and photodynamic therapy (PDT) also have potential applications in diagnosis and visualized therapy of cancers, and hence it is important to investigate the active-targeting ability and in vivo reliability of these nanoprobes. In this work, folic acid (FA)-targeted, photosensitizer (PS)-loaded Fe3O4@NaYF4:Yb/Er (FA-NPs-PS) nanocomposites were synthesized for in vivo T2-weighted MRI and visualized PDT of cancers by modeling MCF-7 tumor-bearing nude mice. By measuring the upconversion luminescence (UCL) and fluorescence emission spectra, the as-prepared FA-NPs-PS nanocomposites showed near-infrared (NIR)-triggered PDT performance due to the production of a singlet oxygen species. Moreover, by tracing PS fluorescence in MCF-7, HeLa cells and in MCF-7 tumors, the FA-targeted nanocomposites demonstrated good targeting ability both in vitro and in vivo. Under the irradiation of a 980 nm laser, the viabilities of MCF-7 and HeLa cells incubated with FA-NPs-PS nanocomposites could decrease to about 18.4% and 30.7%, respectively, and the inhibition of MCF-7 tumors could reach about 94.9%. The transverse MR relaxivity of 63.79 mM-1 s-1 (r2 value) and in vivo MR imaging of MCF-7 tumors indicated an excellent T2-weighted MR performance. This work demonstrated that FA-targeted MRI/PDT nanoprobes are effective for in vivo diagnosis and visualized therapy of breast cancers. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr01932j