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1

Synergistic Antimicrobial Activities of Folic Acid Antagonists and Nucleoside Analogs?  

PubMed Central

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

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

2010-01-01

2

Folic Acid  

MedlinePLUS

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

3

Folic Acid  

MedlinePLUS

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

4

Folic acid  

MedlinePLUS

Folic acid is a water-soluble B vitamin. Since 1998, it has been added to cold cereals, flour, breads, ... law. Foods that are naturally high in folic acid include leafy vegetables (such as spinach, broccoli, and ...

5

Folic Acid  

MedlinePLUS

... acid. Talk to your doctor about how much folic acid you need if you: Are taking medicines used to treat: Epilepsy Type 2 diabetes Rheumatoid arthritis , lupus , psoriasis , asthma , and inflammatory bowel disease Have kidney disease ...

6

Folic acid - test  

MedlinePLUS

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

7

Folic Acid and Pregnancy  

MedlinePLUS

... Flu Pregnancy Precautions Checkups: What to Expect Folic Acid and Pregnancy KidsHealth > Parents > Pregnancy & Newborn Center > Your ... before conception and during early pregnancy . About Folic Acid Folic acid, sometimes called folate, is a B ...

8

Facts about Folic Acid  

MedlinePLUS

... Information For... Media Policy Makers Facts About Folic Acid Language: English Español (Spanish) Recommend on Facebook Tweet ... of the baby's brain and spine. About folic acid Folic acid is a B vitamin. Our bodies ...

9

Folic Acid Quiz  

MedlinePLUS

... Global Activities Information For... Media Policy Makers Folic Acid Quiz Language: English Español (Spanish) Recommend on Facebook ... button beside the question. Good Luck! 1. Folic acid is: A a B vitamin B a form ...

10

Folate Nutrigenetics: A Convergence of Dietary Folate Metabolism, Folic Acid Supplementation, and Folate Antagonist Pharmacogenetics  

Microsoft Academic Search

Folate (Vitamin B9, Folic acid, folinic acid, folacin, pteroyglutamic acid) is essential for life-sustaining proc- esses of DNA synthesis, replication, and repair which are naturally present in common foods such as peas, oranges, broc- coli, and whole-wheat products. Folate levels have been associated with birth defects, cardiovascular disease, and many other important healthcare issues, which has resulted in government-mandated food

Brian Meshkin; Kenneth Blum

2007-01-01

11

Folic Acid: Data and Statistics  

MedlinePLUS

... pregnancy. [ Read article ] Use of Supplements Containing Folic Acid Among Women of Childbearing Age -- United States 2007 ... women of childbearing age: 40% reported taking folic acid daily. 81% reported awareness of folic acid. 12% ...

12

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...

13

Folic Acid Questions and Answers  

MedlinePLUS

... smaller round pills. A single serving of many breakfast cereals also has the amount of folic acid ... vitamin when you: Brush your teeth, OR Eat breakfast, OR Finish your shower, OR Brush your hair, ...

14

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

Microsoft Academic Search

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

JANE C. WRIGHT

1952-01-01

15

Folic acid and birth defect prevention  

MedlinePLUS

Prevention of birth defects with folic acid (folate) ... There is good evidence that taking folic acid before and during pregnancy can reduce the risk of certain birth defects ( spina bifida , anencephaly , and some heart defects). Experts recommend taking 400 ...

16

21 CFR 172.345 - Folic acid (folacin).  

Code of Federal Regulations, 2011 CFR

...acid (folacin). Folic acid (CAS Reg. No. 59-30-3...conditions: (a) Folic acid is the chemical N ...amino]benzoyl]-L -glutamic acid. (b) Folic acid...acid may be added, at levels not to exceed 400...

2011-04-01

17

Homocysteine, Folic Acid and Cardiovascular Disease  

MedlinePLUS

Homocysteine, Folic Acid and Cardiovascular Disease Updated:Mar 18,2014 AHA Recommendation The American Heart Association has not yet called hyperhomocysteinemia ( ... We don't recommend widespread use of folic acid and B vitamin supplements to reduce the risk ...

18

Is folic acid good for everyone?  

Microsoft Academic Search

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

A David Smith; Young-in Kim; Helga Refsum

19

Intestinal transport of zinc and folic acid: a mutual inhibitory  

Microsoft Academic Search

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

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

20

Is folic acid good for everyone?  

PubMed

Fortification of food with folic acid to reduce the number of neural tube defects was introduced 10 y ago in North America. Many countries are considering whether to adopt this policy. When fortification is introduced, several hundred thousand people are exposed to an increased intake of folic acid for each neural tube defect pregnancy that is prevented. Are the benefits to the few outweighed by possible harm to some of the many exposed? In animals, a folic acid-rich diet can influence DNA and histone methylation, which leads to phenotypic changes in subsequent generations. In humans, increased folic acid intake leads to elevated blood concentrations of naturally occurring folates and of unmetabolized folic acid. High blood concentrations of folic acid may be related to decreased natural killer cell cytotoxicity, and high folate status may reduce the response to antifolate drugs used against malaria, rheumatoid arthritis, psoriasis, and cancer. In the elderly, a combination of high folate levels and low vitamin B-12 status may be associated with an increased risk of cognitive impairment and anemia and, in pregnant women, with an increased risk of insulin resistance and obesity in their children. Folate has a dual effect on cancer, protecting against cancer initiation but facilitating progression and growth of preneoplastic cells and subclinical cancers, which are common in the population. Thus, a high folic acid intake may be harmful for some people. Nations considering fortification should be cautious and stimulate further research to identify the effects, good and bad, caused by a high intake of folic acid from fortified food or dietary supplements. Only then can authorities develop the right strategies for the population as a whole. PMID:18326588

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

2008-03-01

21

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 ...

22

Folic acid in ruminant nutrition: a review.  

PubMed

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

Ragaller, Veronika; Hüther, Liane; Lebzien, Peter

2009-01-01

23

Folic acid in general medicine and dermatology.  

PubMed

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

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

2007-01-01

24

Neural Tube Defects, Folic Acid and Methylation  

PubMed Central

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

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

2013-01-01

25

Contemporary issues surrounding folic Acid fortification initiatives.  

PubMed

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

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

2014-12-01

26

Contemporary Issues Surrounding Folic Acid Fortification Initiatives  

PubMed Central

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

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

2014-01-01

27

Preconception counseling and women's compliance with folic acid supplementation.  

PubMed Central

QUESTION: I am counseling patients to take folic acid when they plan pregnancy and during early pregnancy. Is there any proof that counseling really causes women to comply? ANSWER: A recent Motherisk study showed that counseling women who were planning pregnancy about folic acid use is very effective: 71% of those counseled took folic acid, compared with only 17% of those who were not counseled. Images p2057-a PMID:10509214

Pastuszak, A.; Bhatia, D.; Okotore, B.; Koren, G.

1999-01-01

28

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

PubMed Central

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

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

2013-01-01

29

Folic acid fortification and colorectal cancer risk.  

PubMed

The U.S. has been reported as the only country experiencing a decline in incidence rates of colorectal cancer (CRC), despite increasing prevalence of CRC major risk factors, including the Western dietary pattern and obesity. This paper presents a hypothesis that improved folate status in the U.S. is the factor that could most likely explain the seemingly contradictory phenomenon, although a momentary increase in CRC incidence rates was observed in the later 1990s with the initiation of nationwide folic acid fortification. To corroborate this hypothesis, time trends in CRC incidence rates and death rates in the U.S. were plotted by age, race, and gender based on data from the Surveillance, Epidemiology, and End Results (SEER); data were analyzed by simultaneously addressing the following four critical factors: (1) a long induction period between improved folate status and potential protection of CRC; (2) a change in the U.S. Food and Drug Administration regulation in 1973 on the dose of folic acid allowed in supplements; (3) differential impacts of 1973 regulatory change and 1990s mandatory fortification by race; and (4) changes in CRC screening over time in the U.S. Although this type of analysis precludes a definitive conclusion, available evidence suggests that the increase in CRC incidence rates in the later 1990s is unlikely due to folic acid fortification and, assuming a time lag of a decade or longer to see a benefit on CRC, folate appears to be one of the most promising factors that could explain the downward trend of CRC incidence rates in the U.S. PMID:24512932

Keum, NaNa; Giovannucci, Edward L

2014-03-01

30

Folic acid complexes with human and bovine serum albumins.  

PubMed

The interaction of folic acid with human serum (HSA) and bovine serum albumins (BSA) at physiological conditions, using constant protein concentration and various folic acid contents was investigated. FTIR, UV-visible and fluorescence spectroscopic methods as well as molecular modelling were used to analyse folic acid binding sites, the binding constant and the effect on HSA and BSA stability and conformations. Structural analysis showed that folic acid binds HSA and BSA via both hydrophilic and hydrophobic contacts with overall binding constants of Kfolic acid-HSA=8.1 (±0.5)×10(4)M(-1) and Kfolic acid-BSA=1.0 (±0.3)×10(5)M(-1). The number of bound acid molecules per protein was 1.7 (±0.4) for HSA and 1.5 (±0.3) for BSA complexes. Molecular modelling showed participation of several amino acids in folic acid-protein complexes stabilised by hydrogen bonding network. Folic acid complexation altered protein secondary structure by major reduction of ?-helix from 59% (free HSA) to 35% (acid-complex) and 62% (free BSA) to 25% (acid-complex) with an increase in random coil, turn and ?-sheet structures indicating protein unfolding. The results suggest that serum albumins might act as carrier proteins for folic acid in delivering it to target molecules. PMID:25212350

Bourassa, P; Hasni, I; Tajmir-Riahi, H A

2011-12-01

31

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...

32

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

Microsoft Academic Search

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

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

1986-01-01

33

Folate during reproduction: the Canadian experience with folic acid fortification  

PubMed Central

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

Lindzon, Gillian

2007-01-01

34

The neurology of folic acid deficiency.  

PubMed

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

Reynolds, E H

2014-01-01

35

21 CFR 862.1295 - Folic acid test system.  

Code of Federal Regulations, 2011 CFR

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

2011-04-01

36

21 CFR 862.1295 - Folic acid test system.  

Code of Federal Regulations, 2013 CFR

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

2013-04-01

37

21 CFR 862.1295 - Folic acid test system.  

Code of Federal Regulations, 2012 CFR

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

2012-04-01

38

Folic Acid for the Prevention of Colorectal Adenomas  

Microsoft Academic Search

Results During the first 3 years, 987 participants (96.7%) underwent colonoscopic follow-up, and the incidence of at least 1 colorectal adenoma was 44.1% for folic acid (n=221) and 42.4% for placebo (n=206) (unadjusted risk ratio (RR), 1.04; 95% con- fidence interval (CI), 0.90-1.20; P=.58). Incidence of at least 1 advanced lesion was 11.4% for folic acid (n=57) and 8.6% for

A Randomized Clinical Trial; Bernard F. Cole; John A. Baron; Robert S. Sandler; Robert W. Haile; Dennis J. Ahnen; Robert S. Bresalier; Robert W. Summers; Richard I. Rothstein; Carol A. Burke; Dale C. Snover; Timothy R. Church; John I. Allen; Douglas J. Robertson; Gerald J. Beck; John H. Bond; Tim Byers; Jack S. Mandel; Leila A. Mott; Loretta H. Pearson; Elizabeth L. Barry; Judy R. Rees; Norman Marcon; Fred Saibil; Magne Ueland

2007-01-01

39

Chemiluminescence flow sensor for folic acid with immobilized reagents.  

PubMed

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

Song, Z; Zhou, X

2001-11-01

40

Folic Acid May Help Ward Off Stroke in People with High Blood Pressure  

MedlinePLUS

... features on this page, please enable JavaScript. Folic Acid May Help Ward Off Stroke in People With ... Monday, March 16, 2015 Related MedlinePlus Pages Folic Acid High Blood Pressure Stroke SUNDAY, March 15, 2015 ( ...

41

Metabolic interrelationships between folic acid, vitamin B12 and the citrovorum factor  

E-print Network

METABOLIC INTERRELATIONSHIPS BETWEEN FOLIC ACID, VITAMIN B AND THE CITROVORUM FACTOR A Thesis by Vasant Manilal Doctor Approved as to style and content by METABOLIC INTERRELATIONSHIPS BETWEEN FOLIC ACID, VITAMIN B12 AND THE CITROVORUM FACTOR... citrovorum factor (rep rin t )....................................................................... Conversion of folic acid to citrovorum factor by avian liver homogenates. I . Influence of reducing agents and anaerobiosis...

Doctor, Vasant Manilal

1953-01-01

42

Locating the binding sites of folic acid with milk ?- and ?-caseins.  

PubMed

We located the binding sites of folic acid with milk ?- and ?-caseins at physiological conditions, using constant protein concentration and various folic acid contents. FTIR, UV-visible, and fluorescence spectroscopic methods as well as molecular modeling were used to analyze folic acid binding sites, the binding constant, and the effect of folic acid interaction on the stability and conformation of caseins. Structural analysis showed that folic acid binds caseins via both hydrophilic and hydrophobic contacts with overall binding constants of K(folic acid-?-caseins) = 4.8 (±0.6) × 10(4) M(-1) and K(folic acid-?-caseins) = 7.0 (±0.9) × 10(4) M(-1). The number of bound acid molecules per protein was 1.5 (±0.4) for ?-casein and 1.4 (±0.3) for ?-casein complexes. Molecular modeling showed different binding sites for folic acid on ?- and ?-caseins. The participation of several amino acids in folic acid-protein complexes was observed, which was stabilized by hydrogen bonding network and the free binding energy of -7.7 kcal/mol (acid-?-casein) and -8.1 kcal/mol (acid-?-casein). Folic acid complexation altered protein secondary structure by the reduction of ?-helix from 35% (free ?-casein) to 33% (acid-complex) and 32% (free ?-casein) to 26% (acid-complex) indicating a partial protein destabilization. Caseins might act as carriers for transportation of folic acid to target molecules. PMID:22103859

Bourassa, P; Tajmir-Riahi, H A

2012-01-12

43

Indian perspective on clinical aspects, usage, and guidelines of folic Acid.  

PubMed

Folic acid (pteroylmonoglutamic acid) is the stable, fully oxidized form of folate which is used in food fortification and supplements. Keen interest has been generated in folic acid due to its suggested role in prevention of various disorders. Strong evidence from clinical trials indicates preventive effect of folic acid on both occurrence and recurrence of neural tube defects. It also plays a significant role in mitigating the risk of cardiovascular disorders through homocysteine regulation. In addition, the beneficial effect of folic acid in various types of cancers, neurological disorders, conditions affecting pregnancy, and other clinical conditions has been reported in literature. Various guidelines reinforce the need for women to obtain adequate amount of folic acid either through food fortification or supplements. In India, national guidelines on the proper dose of folic acid to pregnant women are not available. Given its significant beneficial effects on health, awareness should be spread among communities on the usage and benefits of folic acid. PMID:25368455

Paayal, Chobe; Ganesh, Uchit; Shaantanu, Donde

2014-10-01

44

Original article Effects of intramuscular injections of folic acid  

E-print Network

.006) feed intake while no effect (P0.13) of the vitamin supplementation was noted on average daily gain of age, suggesting that the supplement was suboptimal during the growing-finishing period. In a second characteristics. These results indicate that a supplement of folic acid administered by intramuscular injections

Paris-Sud XI, Université de

45

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

ERIC Educational Resources Information Center

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

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

2007-01-01

46

Folic acid-Functionalized Nanoparticles for Enhanced Oral Drug Delivery  

PubMed Central

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

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

2012-01-01

47

21 CFR 172.345 - Folic acid (folacin).  

Code of Federal Regulations, 2014 CFR

...107.100 of this chapter. (f) Folic acid may be added to a medical food, as defined in section 5(b)(3) of the Orphan Drug Act (21 U.S.C. 360ee(b)(3)), at levels not to exceed the amount necessary to meet the distinctive...

2014-04-01

48

21 CFR 172.345 - Folic acid (folacin).  

Code of Federal Regulations, 2012 CFR

...107.100 of this chapter. (f) Folic acid may be added to a medical food, as defined in section 5(b)(3) of the Orphan Drug Act (21 U.S.C. 360ee(b)(3)), at levels not to exceed the amount necessary to meet the distinctive...

2012-04-01

49

21 CFR 172.345 - Folic acid (folacin).  

Code of Federal Regulations, 2013 CFR

...107.100 of this chapter. (f) Folic acid may be added to a medical food, as defined in section 5(b)(3) of the Orphan Drug Act (21 U.S.C. 360ee(b)(3)), at levels not to exceed the amount necessary to meet the distinctive...

2013-04-01

50

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

PubMed Central

Although there is accumulating evidence regarding the additional protective effect of folic acid against adverse pregnancy outcomes other than neural tube defects, these effects have not been elucidated in detail. We evaluated whether folic acid supplementation is associated with favorable maternal and fetal outcomes. This was a secondary analysis of 215 pregnant women who were enrolled in our prior study. With additional data from telephone interviews regarding prenatal folic acid supplementation, existing demographic, maternal and fetal data were statistically analyzed. The concentration of folic acid in maternal blood was significantly higher following folic acid supplementation (24.6 ng/mL vs.11.8 ng/mL). In contrast, homocysteine level in maternal blood decreased with folic acid supplementation (5.5 µmol/mL vs. 6.8 µmol/mL). The rates of both preeclampsia (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.09–0.76) and small for gestational age (SGA; 9.2% vs. 20.0%; OR, 0.42; 95% CI, 0.18–0.99) were lower in the folic acid supplementation group than those in the control group. Other pregnancy outcomes had no association with folic acid supplementation. The findings indicate that folic acid supplementation may help to prevent preeclampsia and SGA. Further studies are warranted to elucidate the favorable effects of folic acid supplementation on pregnancy outcomes. PMID:24842467

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

51

Preventive effects of folic acid supplementation on adverse maternal and fetal outcomes.  

PubMed

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

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

52

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

PubMed

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

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

2014-06-01

53

Imaging Pancreatic Cancer with Folic Acid Terminated Luminescent Silicon Nanocrystals  

NASA Astrophysics Data System (ADS)

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

Erogbogbo, Folarin; Swihart, Mark T.

2010-10-01

54

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

Microsoft Academic Search

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

2002-01-01

55

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

MedlinePLUS

Folic Acid for the Prevention of Infant Neural Tube Defects: U.S. Preventive Services Task Force Recommendation Summaries for Patients ... modern medicine. The full reports are titled “Folic Acid for the Prevention of Neural Tube Defects: U.S. ...

56

The effect of folic acid on ovine fetuses in utero during late gestation.  

PubMed

To investigate whether folic acid would have toxic effects on fetal cardiac, hepatic, and renal functions, this was the first in utero fetal study testing acute effects of folic acid at the last third of gestation. Folic acid (5?mg/day) or 0.9% saline as the control was intragastricly administrated into pregnant ewes. Both maternal and fetal blood were analyzed for pH, PO(2), PCO(2), SO(2)%, hemoglobin, hematocrit, glucose, lactic acid, osmolality, Na(+), and K(+) concentrations. Maternal and fetal cardiovascular functions were assessed by examining cardiac enzymes and cardiovascular responses in vivo. Fetal hepatic and renal functions were examined by analysis of biochemistry index and renal excretion. Folic acid did not alter the blood values in both ewes and fetuses. Cardiac enzyme activities remained unchanged, and no alteration in cardiovascular responses was observed. Folic acid did not affect fetal urine volume, urine electrolytes, and osmolality. Enzyme activities related to hepatic and renal functions were not changed. In addition, maternal application of folic acid had no effect on maternal and fetal lipid profile. The results showed that folic acid used (5?mg/day) during the last third of gestation did not cause biochemical changes related to cardiac, hepatic, and renal functions in both maternal and fetal sheep, providing new information for use of folic acid during late pregnancy. PMID:21848402

Mao, Caiping; Liu, Yujuan; Jiang, Shan; Zhou, Anwen; Zhang, Peiwen; Shi, Aiping; Zhang, Hao; Xu, Xiaohui; Xu, Zhice

2012-04-01

57

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...

58

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

ERIC Educational Resources Information Center

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

deRosset, Leslie; Mullenix, Amy; Zhang, Lei

2009-01-01

59

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

ERIC Educational Resources Information Center

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

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

2006-01-01

60

[Fortification of food with folic acid diminishes the number of neural tube defects].  

PubMed

A recent study from a research group from Quebec showed a strong decrease in the number of births affected by a neural tube defect since folic acid fortification was introduced in Canada. The prevalence decreased from 1.58 neural tube defects per 1000 births before the introduction of folic acid fortification to 0.86 per 1000 births in the period of complete fortification. Although folic acid fortification of staple food is probably the most effective way to decrease the incidence of neural tube defects, more knowledge about possible health risks should be obtained before fortification is introduced. More research is needed to determine which population groups are at risk of possible negative effects of folic acid fortification and at which level of fortification. Until then, it is important to generate more attention and publicity in order to increase awareness and knowledge concerning folic acid and to promote its use before and after conception. PMID:18320941

Brouwer, I A

2008-01-26

61

Release of folic acid in mesoporous NFM-1 silica.  

PubMed

Mesoporous NFM-1 silica with folic acid as template was prepared taking advantage of the supramolecular self-assembly of pterin groups and their abilities to form hexagonal liquid crystal phases. NFM-1 materials with the varied morphologies such as fiber, chiral twisting long-rod, gyroid, and amorphous particles were prepared by varying the amount of the co-structure directing agent, stirring speed and changing pH value of the synthesis. The release kinetics of NFM-1 samples with different morphologies were studied in phosphate buffer with pH = 7.4 in 37 degrees C under stirring. All the release kinetic curves are fitted by the power law and Higuchi equations. The fitting of the power law equation was separately done as for the released amount up to 60% or 100%. The materials show slow, long-term and sustained release of folic acid from mesoporous NFM-1 silica, which establishes a new foundation for the potential application in drug delivery and bioimaging. PMID:21137944

Zhou, Chunfang; Garcia-Bennett, Alfonso E

2010-11-01

62

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...

63

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

PubMed Central

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

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

2014-01-01

64

[Does 5-methyltetrahydrofolate offer any advantage over folic acid?].  

PubMed

Almost half of the women do not follow the guidelines around folate suppletion before and during pregnancy, despite the proven benefit in the prevention of neural tube defects, miscarriages and premature births. The Belgian Superior Health Council recommends a minimum of 400 micrograms of folic acid or folate suppletion per day from 4 weeks before conception to 8 weeks thereafter. Many studies point to the importance of a wider intake period, more particularly at least 3 months before conception and throughout pregnancy and lactation. In high-risk women 4 mg is recommended until after the first 3 months of pregnancy. Afterwards the usual dose of 400 micrograms is sufficient. About half of the European population appears to have a gene mutation on the gene coding for the production of methylenetetrahydrofolate reductase, the enzyme that is involved in the formation of 5-methyltetrahydrofolate, which is, in his turn, responsible for the conversion of the toxic homocysteine in methionine. Women with such a gene polymorphism have a significantly higher risk to have a miscarriage or a baby with neural tube defects. For this reason, a search for an alternative form of synthetic folic acid supplement "pteroylmonoglutamic acid (PMG)" was conducted, particularly the calcium salt of 5-methyltetrahydrofolate (Metafolin). This offers the possibility to deliver the reduced folate immediately, which no longer needs to be converted by the reductase enzyme. Furthermore, this avoids free PMG in the circulation, lowers the risk for drug interactions and a vitamin B2 deficiency will not be masked. Despite clear guidelines regarding dietary supplements before and during pregnancy, their implementation is poor. Not only gynecologists but also GPs and pharmacists, should make more efforts to provide women of childbearing age with personal information. Especially risk groups such as adolescents, low-skilled or less well-off women and immigrants deserve special attention. PMID:23350208

Leemans, L

2012-12-01

65

Folic acid - vitamin and panacea or genetic time bomb?  

PubMed

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

Lucock, Mark; Yates, Zoë

2005-03-01

66

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

PubMed

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

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

2015-02-01

67

Methotrexate : Side effects and the role of folic acid supplementation in psoriasis - A study.  

PubMed

In 50 patients of psoriasis, side effects observed with methotrexate pulse were studied. Folic acid ameliorated majority of the side effects without compromising with the therapeutic efficacy of methotrexate. PMID:20944334

Masuria, B L; Mittal, A; Gupta, L K; Sharma, M; Bansal, N

1997-01-01

68

Partial villous atrophy in nutritional megaloblastic anaemia corrected by folic acid therapy  

PubMed Central

A patient with megaloblastic anaemia due to nutritional folate deficiency is described. Partial villous atrophy and malabsorption of xylose showed progressive improvement to normal with folic acid therapy. Images PMID:5551380

Dawson, D. W.

1971-01-01

69

Effects of preparation and cooking of folic acid-fortified foods on the availability of folic acid in a folate depletion/repletion rat model.  

PubMed

The practice of food fortification with folic acid offers the potential to increase the folate intake of the general population. To fully exploit the potential of fortification for raising folate nutriture, appropriate food vehicles need to be selected. Selection should involve determination of the availability of folic acid as affected by characteristics of the carrier food, food matrix, food preparation, and cooking. The present study investigated the effects of preparation and cooking of a range of folic acid-fortified foods on the folate status of folate-deficient rats. Fifty-six weanling male rats (Wistar strain) were fed a folate-deficient diet containing 1% succinyl sulfathiazole for 28 days. Following depletion, six rats were randomly assigned to each of eight repletion diets containing cooked or uncooked meringue mix, quick bread mix, brownie mix, or pizza base mix. The test foods were fortified with 1400 microg of folic acid/kg of food and incorporated as 19% of the repletion diets. Each of the first four groups was pair-fed a diet containing a cooked fortified food with another group fed the corresponding uncooked fortified food. After a further 28 days, plasma, liver, and kidney folate concentrations were determined by microbiological assay. Mean plasma and liver folate concentrations of rats fed diets containing cooked fortified foods were similar to those of rats fed uncooked fortified foods. Preparation and cooking did not affect the availability of folic acid from the selected cereal-based convenience foods in this rat model system, suggesting that these foods are appropriate vehicles for fortification with folic acid. PMID:11559162

O'Leary, K; Sheehy, P J

2001-09-01

70

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

PubMed Central

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

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

2014-01-01

71

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

PubMed

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

Santos, Leonor Maria Pacheco; Pereira, Michelle Zanon

2007-01-01

72

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

E-print Network

KETHIONINE ~ FOLIC ACID ~ VITAMIN Big AND UNIDENTIFIED FACTORS IN THE NUTRITION OF THE GROWING CHICK A Thesis by Billy E. Welch Appr ed o tyls and content by Chairman oi Committee YATHIONINE y FOLIC ACID ~ VITAMIN Big AND UNIDENTIFIED... factor(s) in these compounds would enhance the utili- sation of this;unino acid. . Becent reports have indicated that vit~n BIB and folic acid are concerned with protein metabolism. More specifically, reports by Stekol (1950) and Bennett (1950...

Welch, Billy E

1951-01-01

73

Development of electrochemical folic acid sensor based on hydroxyapatite nanoparticles  

NASA Astrophysics Data System (ADS)

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.

Kanchana, P.; Sekar, C.

2015-02-01

74

Deaza analogs of folic acid as antitumor agents.  

PubMed

Derivatives of the vitamin folic acid function in the body for the synthesis of thymidylate, purines and amino acids and are necessary for normal metabolism and growth. Methotrexate (MTX), an inhibitor of dihydrofolate reductase (DHFR) is the outstanding example of an antitumor antifolate. MTX is clinically useful in the treatment of childhood leukemia, choriocarcinoma and psoriasis, where it corrects abnormal growth, and in rheumatoid arthritis and other autoimmune diseases where it corrects abnormal immune function. Since 1949, when the chemical synthesis of MTX was reported by workers at the Lederle Laboratories of the American Cyanamid Company, much has been learned about the basis of antifolate cytotoxicity and selectivity. This review will focus on deaza antifolates which are: 1). presently under clinical development and 2). less developed compounds which represent novel approaches. Compounds will be grouped according to their enzyme targets; DHFR, thymidylate synthase (TS) and glycinamide ribonucleotide formyltransferase (GARFT). In addition to inhibition of target enzymes, antifolate membrane transport into cells and conversion to poly-L-gamma-glutamate forms are important considerations in drug design along with the reverse processes, cellular hydrolysis of antifolate poly-L-gamma-glutamates to monoglutamates and the extrusion of the monoglutamates through the cell membrane. These processes can be modulated by competition with folates. PMID:14529545

Kisliuk, R L

2003-01-01

75

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

Microsoft Academic Search

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

Rashmi Tupe; Vaishali Agte

2010-01-01

76

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

PubMed

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

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

2013-01-01

77

Folic acid attenuates hyperhomocysteinemia-induced glomerular damage in rats.  

PubMed

The present study investigated whether lowering plasma homocysteine (Hcy) with folic acid (FA) could attenuate hyperhomocysteinemia (HHcy)-associated glomerular damage and possible mechanisms. The HHcy animal model was established by intragastric administration with l-methionine in rats. FA was also given intragastrically. Plasma Hcy and creatinine and urinary albumin were measured. Histological and ultrastructural changes were observed by light and electron microscopes. The expression of alpha-smooth muscle actin (?-SMA), proliferating cell nuclear antigen (PCNA) and transforming growth factor-beta1 (TGF-?1) in the kidney was examined by immunohistochemical staining and western blot analysis. The administration of l-methionine induced HHcy in rats. The HHcy rats developed glomerulosclerosis and fibrosis. Plasma creatinine concentration and urinary albumin excretion were also significantly increased in HHcy rats. Effacement and extensively fusion of podocyte foot process was observed in HHcy rats, which was associated with decreased expression of nephrin protein in renal cortex of HHcy rats. Supplementation with FA lowered plasma Hcy significantly. Plasma creatinine concentration and urinary albumin excretion were also significantly attenuated by FA. Morphologically, HHcy-associated glomerulosclerosis, fibrosis, podocyte foot process effacement and loss of podocyte nephrin, were significantly improved by FA. The expressions of ?-SMA, PCNA and TGF-?1 were increased in renal cortex of HHcy rats, and which were also partially reversed by FA. These data suggest that elevated plasma Hcy is an important pathogenic factor for glomerular damage. Lowering plasma Hcy by FA can inhibit TGF-?1 expression and attenuate HHcy-induced glomerular damage. PMID:23859838

Cao, Lu; Lou, Xiaoying; Zou, Zhaoxia; Mou, Nana; Wu, Weikang; Huang, Xiongqing; Tan, Hongmei

2013-09-01

78

Folic acid intestinal absorption in newborn rats at 21 day postpartum: effects of maternal ethanol consumption.  

PubMed

This study was designed to examine the effects of prenatal and postnatal exposure of ethanol in the in vivo absorption of free folic acid in the small intestine in pups rats at the 21st day after birth. The rats were accustomed to increasing amounts of ethanol (5 to 20%, vol/vol) in tap water for 1 month. During pregnancy and suckling period, ethanol-fed dams were assigned again to ethanol 20% in drinking water. Two sets of experiments were performed. In the first set, jejunal free folic acid absorption in control group and litters nursed by dams receiving ethanol showed a gradual increase along with the increase of perfusion time at all the assayed concentrations. In general, in litters of ethanol-fed dams, jejunal free folic acid absorption expressed as nmol/intestinal surface, nmol/g tissue wet weight and nmol/g tissue dry weight were higher than in control animals. In the second set of experiments, in distal ileum loops, free folic acid absorption did not occur in control pups, but appeared in litters exposed to ethanol. Milk folic acid levels are significantly decreased in ethanol-treated dams. However, only a slight decrease in the serum folic acid levels occurs in litters of ethanol-fed dams. In conclusion, the results obtained in the present work suggested a different pattern of free folic acid absorption in distal ileum for the two groups. The exposure of rats to ethanol during the pregnancy and suckling period, can affect postnatal development of intestinal functions and could play a role in the genesis of malnutrition observed in the infant. PMID:10374925

Tavares, E; Gomez-Tubio, A; Murillo, M L; Carreras, O

1999-01-01

79

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

PubMed

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

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

2014-04-01

80

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

PubMed Central

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

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

2013-01-01

81

Folic acid and human reproduction—ten important issues for clinicians  

PubMed Central

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

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

2011-01-01

82

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...

83

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

Microsoft Academic Search

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

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

84

The use of folic acid supplementation in psoriasis patients receiving methotrexate: a survey in the United Kingdom.  

PubMed

There is little literature on the use of folic acid supplementation in psoriasis patients being treated with methotrexate. Under the auspices of the British Association of Dermatologists we surveyed, using a questionnaire, the use of folic acid supplementation with methotrexate therapy for psoriasis by dermatologists in the UK. Six-hundred and fifteen questionnaires were sent and 153 responses were received (25%). One-hundred and fourteen of the responders (75%) used folic acid supplementation with methotrexate in psoriasis patients. Thirty (26%) of these used folic acid supplementation in all patients taking methotrexate and 84 (74%) used folic acid only under certain circumstances, the most common of which was an elevated erythrocyte mean corpuscular volume. Forty-six per cent of respondents believed that folic acid supplementation reduced nausea and 60% believed that folic acid did not interfere with the efficacy of methotrexate. A wide variety of dosing regimens were used for folic acid supplementation. In the absence of guidelines and controlled trials, there is great variation in the indication for use, dosing regimens used and beliefs regarding methotrexate supplementation for psoriasis. Randomized controlled trials are necessary to address these questions. PMID:10971481

Kirby, B; Lyon, C C; Griffiths, C E; Chalmers, R J

2000-06-01

85

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

PubMed

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

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

2011-11-01

86

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

PubMed Central

A cross-sectional community-based study with analytic component was conducted among Ethiopian women during June-July 2005 to assess the magnitude of anaemia and deficiencies of iron and folic acid and to compare the factors responsible for anaemia among anaemic and non-anaemic cases. In total, 970 women, aged 15-19 years, were selected systematically for haematological and other important parameters. The overall prevalence of anaemia, iron deficiency, iron-deficiency anaemia, deficiency of folic acid, and parasitic infestations was 30.4%, 50.1%, 18.1%, 31.3%, and 13.7% respectively. Women who had more children aged less than five years but above two years, open-field toilet habits, chronic illnesses, and having intestinal parasites were positively associated with anaemia. Women who had no formal education and who did not use contraceptives were negatively associated with anaemia. The major determinants identified for anaemia were chronic illnesses [adjusted odds ratio (AOR)=1.1, 95% confidence interval (CI) 1.15-1.55), deficiency of iron (AOR=0.4, 95% CI 0.35-0.64), and deficiency of folic acid (AOR=0.5, 95% CI 0.50-0.90). The odds for developing anaemia was 1.1 times more likely among women with chronic illnesses, 60% more likely in the iron-deficient and 40% more likely in the folic acid-deficient than their counterparts. One in every three women had anaemia and deficiency of folic acid while one in every two had iron deficiency, suggesting that deficiencies of both folic acid and iron constitute the major micronutrient deficiencies in Ethiopian women. The risk imposed by anaemia to the health of women ranging from impediment of daily activities and poor pregnancy outcome calls for effective public-health measures, such as improved nutrient supplementation, health education, and timely treatment of illnesses. PMID:20824979

2010-01-01

87

Effects of intraperitoneally administered folic Acid on the healing of repaired tibial nerves in rats.  

PubMed

Background?Complete nerve regeneration and clinical healing remain a challenge despite considerable advances in the treatment of peripheral nerve injuries. To improve nerve regeneration, several experimental molecular procedures have been attempted. This study aimed to investigate the effects of folic acid on peripheral nerve healing after transection and end-to-end suture repair of the tibial nerve in rats. Methods?In this study, 20 adult male Wistar Albino rats weighing 225 to 250?g were used. The right tibial nerves of 20 rats were explored, transected, and sutured using the end-to-end technique. The rats were randomly allocated to either the intraperitoneally administered folic acid group (test group) or the control group. Preoperative and 6-week postoperative neurophysiological studies were performed by the same researcher. Myelin-sheathed axons were counted. Results?The results demonstrated that the folic acid-treated group exhibited improved electromyographic results compared with the control group. Histological evaluation revealed that the axons were well preserved and that the axon quantity and density were increased in the test group compared with the control group. Quantitative results also increased in the test group compared with the control group (p?=?0.001). Conclusion?In this study, 6-week intraperitoneal administration of 80 µg/kg of folic acid significantly improved peripheral nerve healing. Histological analysis of the group that received folic acid revealed increased axon myelination with little granular tissue or fibrosis. We propose that folic acid supplementation may be an effective component of peripheral nerve injury treatment. PMID:25423028

Harma, Ahmet; Sahin, Mehmet Sukru; Zorludemir, Suzan

2015-03-01

88

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...

89

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

PubMed Central

Monozygous twin 14-year-old mentally retarded boys with the fragile X syndrome were treated either with 10 mg folic acid by mouth daily or with a placebo for three test periods of 3-month duration each in a blind study. For each twin, tests of cognitive functioning, reading, spelling, and math skills, and linguistic and perceptual skills were compared. Although there was considerable variation in performance on these tests during the two baseline periods, there were no observable beneficial effects of therapy. The routine use of folic acid in patients with established mental retardation and the fragile X syndrome is not indicated. PMID:3890529

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

1985-01-01

90

Effect of folic acid supplementation on oxidative gastric mucosa damage and acid secretory response in the rat  

PubMed Central

Objective: This study investigated the antioxidative and antisecretory properties of folic acid in the rats’ stomach. Materials and Methods: Male Wistar rats were treated with 2 mg/kg diet of folic acid for 21 days. Gastric ulceration was induced by indomethacin, scored, and assayed to determine the concentration of total protein, mucus, malondialdehyde (MDA), catalase (CAT) and superoxide dismutase (SOD) in homogenized samples. Normal saline and Ranitidine treated group served as negative and positive control, respectively. Basal and stimulated acid secretion was measured by continuous perfusion method. Result: Indomethacin caused severe damage to the rats’ stomach with an ulcer index of 4.32 ± 0.13, increase in MDA concentration and reduction in the concentration of protein, mucus, catalase and superoxide dismutase (P < 0.001). Pre-treatment with folic acid prevented the formation of ulcers by 32%, and attenuated the inhibition of mucus by 14%, CAT, 51% and SOD, 150%. Ranitidine afforded 56% prevention in ulcer formation with 67%, 55% and 78% attenuation of the inhibition of mucus, CAT and SOD, respectively, by indomethacin. While indomethacin-induced lipid peroxidation was attenuated by 58% reduction in MDA concentration on pretreatment with folic acid, Ranitidine offered 65% reduction. Basal and stimulated acid secretions were significantly reduced in the treated when compared with control animals. Folic acid produced a 21% reduction in the basal acid output when compared with the control animals (P < 0.05), and 140% reduction in histamine-induced acid response. Conclusion: The results indicate the gastroprotective activity of folic acid due its antioxidative and anti-secretory properties. PMID:22022004

Ajeigbe, K. O.; Olaleye, S. B.; Oladejo, E. O.; Olayanju, A. O.

2011-01-01

91

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

SciTech Connect

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

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

2006-03-01

92

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

Microsoft Academic Search

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

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

93

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 ...

94

Serum folic acid and RFC A80G polymorphism in Alzheimer's disease and vascular dementia.  

PubMed

Low level of vitamin B12 and folic acid has been reported to play an important role in the pathogenesis of Alzheimer's disease (AD) and vascular dementia (VaD). Serum folic acid and vitamin B12 were assayed in 80 AD and 50 VaD cases and in 120 healthy controls. The reduced folate carrier (RFC1) gene, rs1051266, which encodes the RFC 1, protein was analyzed for polymorphism by polymerase chain reaction-restriction fragment length polymorphism. It was observed that the patients having folic acid <8.45 ng/mL had 2.4 (95% confidence interval [CI]: 1.4-4.5) times higher odds of having AD and 2.1 (95% CI: 1.1-4.2) times higher odds of having VaD than patients having folic acid ?8.45 ng/mL. Serum vitamin B12 level did not show any such statistically significant effect in altering the odds. No direct association was found between variant (G) allele or genotype of rs1051266 with AD and VaD cases. On serum folate level no association was observed with gene polymorphism. PMID:24554143

Mansoori, Nasim; Tripathi, Manjari; Alam, Rizwan; Luthra, Kalpana; Sharma, Sumit; Lakshmy, Ramakrishnan; Kalaivani, Mani; Mukhopadhyay, Asok K

2014-02-01

95

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...

96

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

Microsoft Academic Search

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

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

2006-01-01

97

Harvard study finds folic acid, vitamins B6 and 12 do not affect colorectal adenoma risk  

Cancer.gov

Combined folic acid, vitamin B6 and vitamin B12 supplements had no statistically significant effect on the risk of colorectal adenoma among women who were at high risk for cardiovascular disease, according to a Harvard Medical School study published October 12 in the Journal of the National Cancer Institute. The Harvard Medical School is a component of the Dana-Farber Cancer Institute.

98

Multi-institute study finds folic acid may reduce some childhood cancers  

Cancer.gov

Folic acid fortification of foods may reduce the incidence of the most common type of kidney cancer and a type of brain tumors in children, finds a new study from the University of Minnesota and Washington University in St. Louis. Incidence reductions were found for Wilms' tumor, a type of kidney cancer, and primitive neuroectodermal tumors (PNET), a type of brain cancer.

99

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...

100

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

PubMed

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

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

2005-12-01

101

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...

102

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...

103

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...

104

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

PubMed

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

Iyer, Ramya; Tomar, Sudhir Kumar

2013-05-01

105

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

PubMed Central

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

Mahajan, Sanket K.; Aundhakar, Swati C.

2015-01-01

106

Folic acid supplementation for the prevention of recurrence of colorectal adenomas: metaanalysis of interventional trials.  

PubMed

Conflicting data have emerged from preclinical and clinical studies that examined the relationship between folic acid and the risk of recurrence of colorectal adenomas. To determine precisely that relation, we planned this metaanalysis. We searched literature to identify interventional randomized, placebo-controlled studies where folic acid in specific dose and for specific duration was administered to evaluate its effect on the recurrence of adenomatous colorectal polyps. Five eligible trials were identified. The total number of patients with history of colorectal adenomas in the folate and the placebo groups was 805 and 775 patients, respectively. Our analysis showed that folate supplementation had no protective effects on the recurrence of colorectal adenomas [odds ratio = 1.08 (95% CI; 0.87, 1.33; P = 0.49)], nor has a positive outcome on the number of recurrent polyps per patient (P = 0.41). Examination of folic acid dose effect showed that the two studies that have used folic acid as 1 mg/day favored folic acid over placebo with an odds ratio of 0.62 (95% CI; 0.48, 0.80). However, the overall effect for all included studies was not significant [odds ratio = 0.78 (95% CI; 0.49, 1.24; P = 0.30)]. We found significant heterogeneity between trials, moreover, included trials exhibit inconsistency in methodological quality. The present metaanalysis has failed to show potential benefit for folate supplementation. Future trials should examine the effect of different dosage and duration. Moreover, the confounding effect of dietary and life style habits should be carefully controlled. PMID:19757214

Ibrahim, Ezzeldin M; Zekri, Jamal M

2010-09-01

107

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

PubMed

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

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

2010-01-01

108

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

NASA Astrophysics Data System (ADS)

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

Nan, Alexandrina; Turcu, Rodica; Liebscher, Jürgen

2013-11-01

109

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

SciTech Connect

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

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

2013-11-13

110

Folic acid supplementation, dietary folate intake during pregnancy and risk for spontaneous preterm delivery: a prospective observational cohort study  

PubMed Central

Background Health authorities in numerous countries recommend periconceptional folic acid to pregnant women to prevent neural tube defects. The objective of this study was to examine the association of folic acid supplementation during different periods of pregnancy and of dietary folate intake with the risk of spontaneous preterm delivery (PTD). Methods The Norwegian Mother and Child Cohort Study is a population-based prospective cohort study. A total of 65,668 women with singleton pregnancies resulting in live births in 1999–2009 were included. Folic acid supplementation was self-reported from 26 weeks before pregnancy until week 24 during pregnancy. At gestational week 22, the women completed a food frequency questionnaire, which allowed the calculation of their average total folate intake from foods and supplements for the first 4–5 months of pregnancy. Spontaneous PTD was defined as the spontaneous onset of delivery between weeks 22+0 and 36+6 (n?=?1,628). Results The median total folate intake was 266 ?g/d (interquartile range IQR 154–543) in the overall population and 540 ?g/d (IQR 369–651) in the supplement users. Eighty-three percent reported any folic acid supplementation from <8 weeks before to 24 weeks after conception while 42% initiated folic acid supplementation before their pregnancy. Cox regression analysis showed that the amount of folate intake from the diet (hazard ratio HR 1.16; confidence interval CI 0.65-2.08) and from the folic acid supplements (HR 1.04; CI 0.95-1.13) was not significantly associated with the risk of PTD. The initiation of folic acid supplementation more than 8 weeks before conception was associated with an increased risk for PTD (HR 1.19; CI 1.05-1.34) compared to no folic acid supplementation pre-conception. There was no significant association with PTD when supplementation was initiated within 8 weeks pre-conception (HR 1.01; CI 0.88-1.16). All analyses were adjusted for maternal characteristics and socioeconomic, health and dietary variables. Conclusions Our findings do not support a protective effect of dietary folate intake or folic acid supplementation on spontaneous PTD. Pre-conceptional folic acid supplementation starting more than 8 weeks before conception was associated with an increased risk of PTD. These results require further investigation before discussing an expansion of folic acid supplementation guidelines. PMID:23937678

2013-01-01

111

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

PubMed

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

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

2011-02-01

112

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

PubMed Central

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

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

2014-01-01

113

The effect of folic acid deficiency and MTHFR C677T polymorphism on chromosome damage in human lymphocytes in vitro.  

PubMed

We performed a comprehensive study on the genotoxic and cytotoxic effects of in vitro folic acid deficiency on primary human lymphocytes. Lymphocytes were cultured in medium containing 12-120 nM folic acid for 9 days in a novel cytokinesis-block micronucleus (CBMN) assay system (n = 20). Besides identifying optimal folic acid concentrations for in vitro genomic stability, we tested the hypothesis that lymphocytes from individuals homozygous for the C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism (TTs, n = 10) are protected against chromosome damage relative to controls (CCs, n = 10) under conditions of folic acid deficiency. This hypothesis is based on the assumption that reduced MTHFR activity in TT lymphocytes causes a diversion of 5,10-methylene tetrahydrofolate toward thymidine synthesis, which minimizes uracil-induced double-stranded DNA breakage. Cells were scored for micronuclei, apoptosis, necrosis, nucleoplasmic bridges, and nuclear budding. The latter two endpoints are indicative of chromosome rearrangements and gene amplification, respectively, and to the best of our knowledge, this is the first report of their association with folic acid concentration. Folic acid concentration correlated significantly (P < 0.0001) and negatively (r, -0.63 to -0.74) with all markers of chromosome damage, which were minimized at 60-120 nM folic acid, much greater than concentrations assumed "normal," but not necessarily optimal in plasma. Two-way ANOVA revealed no effect of the MTHFR genotype on any of the endpoints. Results show that the C677T polymorphism does not affect the ability of a cell to resist chromosome damage induced by folic acid deficiency in this in vitro system. PMID:11588136

Crott, J W; Mashiyama, S T; Ames, B N; Fenech, M

2001-10-01

114

Effect of methionine, methionine hydroxy analogue, vitamin B?? and folic acid on blood and liver glutathione content in chicks  

E-print Network

~ GF METHIOEIEE~ METHIOEIEE ZQRGKY AEALOGUE~ ~ B~ AED FOLIC ACID OE BLOOD AED LXVER GAGEE COETEET IE CHICKS A Thesis Approved ss o tyle and. content by: / irmgn Q C~ttee Nsy 1954 LIBRARY 4 & N COLLEGE OF TEXAS ~ OF NETBIOEIEE, NETBIONINE... HYDROXY AEALOGUE~ VITAlGTI BIB AND FOLIC ACID 05 BLOOD AHD LIVER GIVBLHBOTIE COTITERT III CHICKS A Thesis Sabit Gsbsy Submitted to the Graduate School of the Agricultural and Mechanical College of Texas in partial fulfillment of the requirements...

Gabay, Sabit

1954-01-01

115

Dietary folic acid activates AMPK and improves insulin resistance and hepatic inflammation in dietary rodent models of the metabolic syndrome.  

PubMed

The AMP activated kinase plays an important role in metabolic control, and pharmacologic enhancement of AMPK activity is used to improve insulin resistance. We hypothesized that high dose of folic acid supplementation might improve insulin sensitivity and hepatic inflammation and examined this by a dietary intervention in (a) the high fat fed rat model of the metabolic syndrome, which shows sole hepatic steatosis as well as (b) in rats fed with a high cholesterol, high cholate diet inducing nonalcoholic steatohepatitis (NASH). Male Wistar rats were fed with folic acid supplemented (40?mg/kg) high fat diet [based on lard, fat content 25% (wt/wt)] or NASH inducing diet (containing 15% fat, 1.25% cholesterol, 0.5% sodium cholate). Metabolic profiling was performed by measuring the animals' visceral fat pads, fasting plasma glucose, insulin, and adipokines as well as in vivo insulin tolerance tests. Hepatic steatosis and inflammation were analyzed semiquantitatively by histological analysis. Folic acid supplementation reduced visceral obesity and improved plasma adiponectin levels. In vivo insulin sensitivity was improved, and in HF-FA rats folic acid increased activation of hepatic AMPK. Further, folic acid supplementation improved hepatic inflammation in animals fed with NASH-inducing diet. Dietary folic acid improved parameters of insulin resistance and hepatic inflammation in rodent models. This might be due to an increased AMK activation. PMID:20803414

Buettner, R; Bettermann, I; Hechtl, C; Gäbele, E; Hellerbrand, C; Schölmerich, J; Bollheimer, L C

2010-10-01

116

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

PubMed Central

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

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

2014-01-01

117

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

PubMed

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

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

2014-12-01

118

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

PubMed

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

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

2013-10-01

119

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

PubMed Central

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

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

2013-01-01

120

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

Microsoft Academic Search

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

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

2011-01-01

121

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

Microsoft Academic Search

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

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

2005-01-01

122

Effect of narrowband ultraviolet B phototherapy on serum folic acid levels in patients with psoriasis  

Microsoft Academic Search

Narrowband ultraviolet B phototherapy (NB-UVB) is a widely used modality in the treatment of psoriasis and is generally accepted\\u000a as safe in pregnancy. Previous studies have described photodegradation of serum folate after exposure to UVA radiation but\\u000a the effect of UVB is not known. We studied the effect of NB-UVB phototherapy on serum folic acid levels in patients with psoriasis

Lotfy Taha El-Saie; Ali Ramadan Rabie; Mohammed Ismail Kamel; Ahmad Kamel Seddeik; Mohamed L. Elsaie

2011-01-01

123

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

Microsoft Academic Search

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

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

2010-01-01

124

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

PubMed Central

OBJECTIVE: Epidemiologic evidence indicates that prenatal vitamin supplementation reduces risk for some childhood cancers; however, a systematic evaluation of population-based childhood cancer incidence trends after fortification of enriched grain products with folic acid in the United States in 1996–1998 has not been previously reported. Here we describe temporal trends in childhood cancer incidence in association with US folic acid fortification. METHODS: Using Surveillance, Epidemiology, and End Results program data (1986–2008), we calculated incidence rate ratios and 95% confidence intervals to compare pre- and postfortification cancer incidence rates in children aged 0 to 4 years. Incidence trends were also evaluated by using joinpoint and loess regression models. RESULTS: From 1986 through 2008, 8829 children aged 0 to 4 years were diagnosed with malignancies, including 3790 and 3299 in utero during the pre- and postfortification periods, respectively. Pre- and postfortification incidence rates were similar for all cancers combined and for most specific cancer types. Rates of Wilms tumor (WT), primitive neuroectodermal tumors (PNETs), and ependymomas were significantly lower postfortification. Joinpoint regression models detected increasing WT incidence from 1986 through 1997 followed by a sizable decline from 1997 through 2008, and increasing PNET incidence from 1986 through 1993 followed by a sharp decrease from 1993 through 2008. Loess curves indicated similar patterns. CONCLUSIONS: These results provide support for a decrease in WT and possibly PNET incidence, but not other childhood cancers, after US folic acid fortification. PMID:22614769

Johnson, Kimberly J.; Ross, Julie A.

2012-01-01

125

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

PubMed

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

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

2012-07-01

126

Impact of administration of folic acid on selected indicators of inflammation in patients with primary arterial hypertension.  

PubMed

The results of epidemiological and clinical tests have shown that in patients with primary arterial hypertension, a chronic mild inflammation develops. The purpose of the study was to determine whether administration of folic acid to patients with primary arterial hypertension influences concentrations of indicators of inflammation: hsCRP, sICAM-1 and sVCAM-1. The examination was carried out in 41 patients with primary arterial hypertension, aged 19-65 (21 men and 20 women), without complications of hypertension and/or coexisting diseases. The examined patients were administered 15 mg of folic acid once a day for 45 days. Before and after administration of folic acid, concentrations of folic acid, homocysteine, hsCRP, sICAM-1 and sVCAM-1 in serum were assessed. Concentrations of folic acid and homocysteine were determined using the immunoenzymatic method (Abbott) on an AxSYM analyzer. The level of C-reactive protein (CRP) was determined with an ultra-sensitive turbidimetric assay on a Dimension analyzer (Siemens). Next, concentrations of adhesion particles sICAM-1 and sVCAM-1 were assessed with the ELISA technique (R&D). After the administration of folic acid in patients with primary arterial hypertension, a significant decrease in median concentrations of homocysteine in blood was observed. Simultaneously, the median hsCRP, ICAM-1 and VCAM-1 concentrations in serum in patients with primary arterial hypertension were significantly reduced. Administration of folic acid to persons with primary arterial hypertension in a dose of 15 mg/ day for 45 days caused a decrease in the concentration of homocysteine in serum. That could indirectly result in the decrease in concentrations of the indicators of inflammation (hsCRP, ICAM-1 and VCAM-1), as it is apparent from previous studies that hyperhomocysteinemia stimulates the synthesis of CRP and the expression of adhesion molecules. PMID:25897102

Baszczuk, Aleksandra; Kopczy?ski, Zygmunt; Kopczy?ski, Jaros?aw; Cymerys, Maciej; Thielemann, Anna; Bielawska, Lena; Banaszewska, Anna

2015-01-01

127

Synthesis of folic acid functionalized redox-responsive magnetic proteinous microcapsules for targeted drug delivery.  

PubMed

Folic acid (FA) functionalized magnetic bovine serum albumin (BSA) microcapsules (FA-MBMCs) were prepared by a facile sonochemical method, in which FA molecule was immobilized onto the outer walls of microcapsules as a targeting ligand and oleic acid (OA) modifying Fe3O4 magnetic nanoparticles (OA-Fe3O4 MNPs) were wrapped into the microcapsules. The obtained FA-MBMCs possessed a nice spherical morphology with the mean size of 1.4?m. FA-MBMCs also showed an excellent magnetic and molecular dual-targeted property. Besides, the reductant-triggered diffusion of coumarin 6 suggested superior drug controlled release of FA-MBMCs. PMID:25840270

Li, Zhanfeng; Liu, Songfeng; Wang, Shurong; Qiang, Linhui; Yang, Ting; Wang, Hongyan; Möhwald, Helmuth; Cui, Xuejun

2015-07-15

128

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

Microsoft Academic Search

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

Padmarajaiah Nagaraja; Ramanathapura A Vasantha; Hemmige S Yathirajan

2002-01-01

129

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

PubMed

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

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

2015-01-16

130

Folic acid and melatonin ameliorate carbon tetrachloride-induced hepatic injury, oxidative stress and inflammation in rats  

PubMed Central

This study investigated the protective effects of melatonin and folic acid against carbon tetrachloride (CCl4)-induced hepatic injury in rats. Oxidative stress, liver function, liver histopathology and serum lipid levels were evaluated. The levels of protein kinase B (Akt1), interferon gamma (IFN-?), programmed cell death-receptor (Fas) and Tumor necrosis factor-alpha (TNF-?) mRNA expression were analyzed. CCl4 significantly elevated the levels of lipid peroxidation (MDA), cholesterol, LDL, triglycerides, bilirubin and urea. In addition, CCl4 was found to significantly suppress the activity of both catalase and glutathione (GSH) and decrease the levels of serum total protein and HDL-cholesterol. All of these parameters were restored to their normal levels by treatment with melatonin, folic acid or their combination. An improvement of the general hepatic architecture was observed in rats that were treated with the combination of melatonin and folic acid along with CCl4. Furthermore, the CCl4-induced upregulation of TNF-? and Fas mRNA expression was significantly restored by the three treatments. Melatonin, folic acid or their combination also restored the baseline levels of IFN-? and Akt1 mRNA expression. The combination of melatonin and folic acid exhibited ability to reduce the markers of liver injury induced by CCl4 and restore the oxidative stability, the level of inflammatory cytokines, the lipid profile and the cell survival Akt1 signals. PMID:23374533

2013-01-01

131

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

PubMed Central

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

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

2013-01-01

132

Active tumor targeting of nanomaterials using folic acid, transferrin and integrin receptors.  

PubMed

Folic acid, transferrin and integrin alpha v beta 3 (?v?3) receptors are overexpressed in various cancer cell lines. Ligands having high affinity for these receptors are often conjugated to nanocarriers to facilitate the tumor localization of therapeutic agents. In this review the use of these ligands for targeted delivery using liposomes, dendrimers and (N-(2-hydroxypropyl) methacrylamide) (HPMA) copolymers is discussed. Emphasis is placed on discussing drug delivery systems that have been optimized for in-vitro binding as well as in-vivo pharmacokinetics. Our aim is to understand the various factors influencing the targeting ability of nanocarriers. PMID:21696360

Kolhatkar, Rohit; Lote, Asawari; Khambati, Hiren

2011-09-01

133

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

PubMed

Folic acid plays a critical role in the prevention of chromosome breakage and hypomethylation of DNA. This activity is compromised when Vitamin B12 (B12) concentration is low because methionine synthase activity is reduced, lowering the concentration of S-adenosyl methionine (SAM) which in turn may diminish DNA methylation and cause folate to become unavailable for the conversion of dUMP to dTMP. The most plausible explanation for the chromosome-breaking effect of low folate is excessive uracil misincorporation into DNA, a mutagenic lesion that leads to strand breaks in DNA during repair. Both in vitro and in vivo studies with human cells clearly show that folate deficiency causes expression of chromosomal fragile sites, chromosome breaks, excessive uracil in DNA, micronucleus formation and DNA hypomethylation. In vivo studies show that Vitamin B12 deficiency and elevated plasma homocysteine are significantly correlated with increased micronucleus formation. In vitro experiments indicate that genomic instability in human cells is minimised when folic acid concentration in culture medium is >227nmol/l. Intervention studies in humans show: (a) that DNA hypomethylation, chromosome breaks, uracil misincorporation and micronucleus formation are minimised when red cell folate concentration is >700nmol/l folate; and (b) micronucleus formation is minimised when plasma concentration of Vitamin B12 is >300pmol/l and plasma homocysteine is <7.5micromol/l. These concentrations are achievable at intake levels in excess of current RDIs i.e. more than 200-400microgram folic acid per day and more than 2microgram Vitamin B12 per day. A placebo-controlled study with a dose-response suggests that based on the micronucleus index in lymphocytes, an RDI level of 700microgram/day for folic acid and 7microgram/day for Vitamin B12 would be appropriate for genomic stability in young adults. Dietary intakes above the current RDI may be particularly important in those with extreme defects in the absorption and metabolism of these Vitamins, for which ageing is a contributing factor. PMID:11295154

Fenech, M

2001-04-18

134

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

PubMed Central

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

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

2014-01-01

135

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

PubMed

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

Hamner, Heather C; Tinker, Sarah C

2014-04-01

136

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

E-print Network

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

Ahmad, Sajjad

137

Effects of Prenatal and\\/or Postnatal (Maternal and\\/or Child) Folic Acid Supplementation on the Mental Performance of Children  

Microsoft Academic Search

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

Agata Skórka; Dorota Gieruszczak-Bia?ek; Ma?gorzata Pie?cik; Hania Szajewska

2012-01-01

138

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

Microsoft Academic Search

ABSTRACTIt 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

Agata Skórka; Dorota Gieruszczak-Bia?ek; Ma?gorzata Pie?cik; Hania Szajewska

2011-01-01

139

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

Microsoft Academic Search

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

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

1998-01-01

140

Effect of vitamin C and folic acid on seed vigour response and phenolic-linked antioxidant activity.  

PubMed

Folic acid and vitamin C were used in the concentration range of 0-500muM as exogenous growth enhancers to stimulate pea (Pisum sativum) seedling vigour. The results suggest that a concentration of 50muM folic acid and 500muM vitamin C were optimum in maximally enhancing seed vigour and potentially seedling performance according to both agronomic and biochemical seed vigour parameters. Results indicated that germination percentage, shoot weight, shoot height, and root length were enhanced in folic acid and vitamin C treated plants compared to control plants. The levels of enhanced phenolic content in response to folic acid and vitamin C treatments were highest on days 8 and 10. Evaluation of critical biochemical parameters indicated that the average glucose-6-phosphate dehydrogenase (G6PDH) activity and proline content in response to treatments were higher than control and correlated to enhanced phenolic content and DPPH-based antioxidant activity. Key enzymes, guaiacol peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT) were also higher in response to treatments and correlated to enhanced phenolic content and DPPH-based antioxidant activity. Taken together, these studies support the hypothesis that the proline-linked pentose phosphate pathway stimulates phenolic synthesis and related free-radical scavenging antioxidant activity. Further, this proline-linked pentose phosphate pathway stimulation in response to folic acid and vitamin C was also correlated to antioxidant enzyme response indicated by the stimulation of GPX, SOD, and CAT activities. Therefore, this study indicates the enhancement of seed vigour response by folic acid and vitamin C as reflected in both agronomic and biochemical responses, and this occurred through the stimulation of phenolic-linked antioxidant response that is likely positively modulated through the proline-linked pentose phosphate pathway. PMID:16876400

Burguieres, Elizabeth; McCue, Patrick; Kwon, Young-In; Shetty, Kalidas

2007-05-01

141

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

PubMed Central

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

Sarmah, Swapnalee; Marrs, James A.

2014-01-01

142

Zebrafish retinal defects induced by ethanol exposure are rescued by retinoic acid and folic acid supplement.  

PubMed

Fetal Alcohol Spectrum Disorder (FASD) is caused by prenatal alcohol exposure, producing craniofacial, sensory, motor, and cognitive defects. FASD is highly prevalent in low socioeconomic populations, which are frequently accompanied by malnutrition. FASD-associated ocular pathologies include microphthalmia, optic nerve hypoplasia, and cataracts. The present study characterizes specific retinal tissue defects, identifies ethanol-sensitive stages during retinal development, and dissects the effect of nutrient supplements, such as retinoic acid (RA) and folic acid (FA) on ethanol-induced retinal defects. Exposure to pathophysiological concentrations of ethanol (during midblastula transition through somitogenesis; 2-24 h post fertilization [hpf]) altered critical transcription factor expression involved in retinal cell differentiation, and produced severe retinal ganglion cell, photoreceptor, and Müller glial differentiation defects. Ethanol exposure did not alter retinal cell differentiation induction, but increased retinal cell death and proliferation. RA and FA nutrient co-supplementation rescued retinal photoreceptor and ganglion cell differentiation defects. Ethanol exposure during retinal morphogenesis stages (16-24 hpf) produced retinal defects like those seen with ethanol exposure between 2 and 24 hpf. Significantly, during an ethanol-sensitive time window (16-24 hpf), RA co-supplementation moderately rescued these defects, whereas FA co-supplementation showed significant rescue of optic nerve and photoreceptor differentiation defects. Interestingly, RA, but not FA, supplementation after ethanol exposure could reverse ethanol-induced optic nerve and photoreceptor differentiation defects. Our results indicate that various ethanol-sensitive events underlie FASD-associated retinal defects. Nutrient supplements like retinoids and folate were effective in alleviating ethanol-induced retinal defects. PMID:25541501

Muralidharan, Pooja; Sarmah, Swapnalee; Marrs, James A

2015-03-01

143

Oral supplementation of folic acid for two months reduces total serum homocysteine levels in hyperhomocysteinemic Greek children  

PubMed Central

Background & Aim: Hyperhomocysteimemia is a cardiovascular risk factor even among children. Supplementation of oral folic acid may reduce homocysteine levels to normal. However, data is limited at this point for healthy children and adolescents. Methods: Five hundre and twenty four children participated in the study; Twenty six of them were found to be hyperho mocysteinemic(>95th percentile for age). Twenty of them received 5 mg of folic acid twice per week for two consecutive months while the other six received a diet rich in dietary folate. Results: Serum homocysteine levels were statistically significantly decreased from 13.1 (10-24.2 µmol/L ) to 7.7 (4.9- 15.2 µmol/L), p<0.001. Serum folate levels were significantly rose from 4.3 (3-20 ng/mL) to 16.8 (7-20 ng/mL), p<0.001. On the contrary, no important changes were observed in the above parameters in children to whom a diet rich in folic acid was recommended. Homocysteine levels were found to be positively associated with age (r=0.314, p<0.001), BMI (r=0.192, p<0.001), WC (r = 0.215, p<0.001), simple sugars (r= 0.182, p<0.001 ) and negatively associated with folic acid (r = -0.331, p<0.001), vitamin B12 (r = -0.214, p<0.001) and dietary folic acid (r= -0.228, p=0.003). Conclusions: Oral folic acid 5 mg twice per week may efficiently reduce serum homocysteine levels and increase serum folic acid levels in healthy children with increased homocysteine levels (>95th percentile for age). Hyperhomocysteinemia in childhood may be a predictive factor of cardiovascular disease. In addition, these results may offer more help to health practioners in order to establish more prospective studies to elucidate the relationship between homocysteine, folic acid and heart disease in children. PMID:20596265

Papandreou, D; Malindretos, P; Arvanitidou, M; Makedou, A; Rousso, I

2010-01-01

144

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

PubMed Central

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

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

2013-01-01

145

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

PubMed Central

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

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

2011-01-01

146

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

NASA Astrophysics Data System (ADS)

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

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

2014-04-01

147

Folic Acid  

MedlinePLUS

... and breads. Supplements are sold in tablet and powder form in drug stores and health food stores. ... older women showed that women who drank more alcohol were more likely to have breast cancer. But ...

148

Folic Acid  

MedlinePLUS Videos and Cool Tools

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149

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

150

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

Microsoft Academic Search

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

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

2009-01-01

151

Autocatalytic amplified detection of DNA based on a CdSe quantum dot/folic acid electrochemiluminescence energy transfer system.  

PubMed

In this work, electrochemiluminescence energy transfer (ECL-ET) from CdSe quantum dots (QDs) to folic acid is reported for the first time and applied for amplified detection of DNA by using a novel DNAzyme-mediated autocatalytic system. PMID:25347434

Jie, Guifen; Qin, Yingqiang; Meng, Qingmin; Wang, Jialin

2015-01-01

152

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...

153

Molar ratio iron: zinc and folic acid in Brazilian biscuits and snacks and test for classification using principal component analyses.  

PubMed

The aim of the present work was to evaluate molar ratio iron: zinc and the levels of folic acid in biscuit and snacks commercialized in Brazil, prepared with folic acid and iron fortified flours. These nutrients are important for human nutrition; however, iron can have a negative effect on zinc absorption. Molar ratio iron:zinc can indicate if there will be any problems for absorption of these nutrients. The folic acid content varied from 58 to 433 ?g/100 g and iron and zinc levels varied from 2.9 to 9.4 mg/100 g and from 0.2 to 1.3 mg/100 g, respectively, for 75 analyzed samples. The average iron contents observed in the products and molar ratio iron:zinc (in average 8:1 for biscuits and 12.8:1 for snacks) could result in problems with the zinc absorption. Moreover, principal compo- nent analyses (PCA) indicated low uniformity in the distribution of minerals and vitamin in the majority of the samples, mainly among brands. The results indicated that for the majority of the samples tested folic acid and iron content was higher than expected for flours and could be useful to governmental authorities in their evaluation program of flour fortification. PMID:25799687

Godoy, Adriana Teixeira; Rebelatto, Ana Paula; Borin-Nogueira, Alessandra; Lima-Pallone, Juliana Azevedo

2014-06-01

154

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

Microsoft Academic Search

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

DIMITRI A. CHRISTAKIS; HAROLD P. LEHMANN

155

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

PubMed Central

Many anticancer drugs have been established clinically, but their efficacy can be compromised by nonspecific toxicity and an inability to reach the desired cancerous intracellular spaces. In order to address these issues, researchers have explored the use of folic acid as a targeted moiety to increase specificity of chemotherapeutic drugs. To expand upon such research, we have conjugated folic acid to functionalized poly(ethylene glycol) and subsequently decorated the surface of L-tyrosine polyphosphate (LTP) nanoparticles. These nanoparticles possess the appropriate size (100–500 nm) for internalization as shown by scanning electron microscopy and dynamic light scattering. Under simulated physiological flow, LTP nanoparticles decorated with folic acid (targeted nanoparticles) show a 10-fold greater attachment to HeLa, a cervical cancer cell line, compared to control nanoparticles and to human dermal fibroblasts. The attachment of these targeted nanoparticles progresses at a linear rate, and the strength of this nanoparticle attachment is shown to withstand shear stresses of 3.0 dynes/cm2. These interactions of the targeted nanoparticles to HeLa are likely a result of a receptor-ligand binding, as a competition study with free folic acid inhibits the nanoparticle attachment. Finally, the targeted nanoparticles encapsulated with a silver based drug show increased efficacy in comparison to non-decorated (plain) nanoparticles and drug alone against HeLa cells. Thus, targeted nanoparticles are a promising delivery platform for developing anticancer therapies that over-express the folate receptors (FRs). PMID:22957928

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

2012-01-01

156

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 ...

157

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

Microsoft Academic Search

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

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

2009-01-01

158

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

Microsoft Academic Search

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

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

2009-01-01

159

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...

160

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

PubMed Central

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

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

2011-01-01

161

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

PubMed Central

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

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

162

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

PubMed Central

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-?g 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

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

2014-01-01

163

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

PubMed Central

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

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

2009-01-01

164

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

PubMed

In this work, electrochemically synthesized gold nanoparticles (AuNPs) and ?-polyoxometalate (?-POM) (K7PMO2W9O39 · H2O) were simultaneously doped into electropolymerized polypyrrole (PPy) film using the cyclic voltammetry (CV) technique. Scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS) and CVs were used to characterize the composite films. The PPy-?-POM-AuNPs modified gold (Au) electrode was used to determine folic acid (FA) using square-wave voltammetry (SWV). The modified electrode exhibited excellent electrocatalytic ability to the reduction of FA at 0.3 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

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

2014-10-15

165

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

PubMed

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

Barua, Subit; Kuizon, Salomon; Junaid, Mohammed A

2014-01-01

166

Folic acid attenuates cognitive dysfunction in streptozotocin-induced diabetic rats.  

PubMed

Diabetic cognitive dysfunction is common in patients with diabetes but its pathogenesis is not clear. The aim of the present study is to investigate the role of 5', 10' methylene tetrahydrofolate reductase (MTHFR) in the development of diabetic cognitive impairment and test whether folic acid (FA) supplementation prevents cognitive dysfunction in diabetic rats. In the current study, three months after streptozotocin-induced diabetes onset, rats showed cognitive dysfunction including the prolonged escape latency, the decreased time spent in the target quadrant and the declined number of crossing the platform in Morris water maze test. Diabetic rats also presented elevated plasma homocysteine level and downregulation of MTHFR in hippocampus revealed by Western blotting. The diabetic cognitive dysfunction was attenuated by 30-day dietary FA treatment with a significantly decreased homocysteine level. In conclusion, these results suggest that MTHFR plays a crucial role in diabetic cognitive dysfunction and folate fortification might become a potent therapeutic strategy against diabetic cognitive impairment. PMID:25550933

Yang, Rui; Chen, Rong-Ping; Chen, Hong; Zhang, Hua; Cai, De-Hong

2014-01-01

167

Soft structure formation and cancer cell transport mechanisms of a folic acid-dipeptide conjugate.  

PubMed

Folic acid (FA) is a low-molecular-weight micronutrient, which plays a critical role in the prevention of birth defects and cancers. It is also essential for biochemical pathways responsible for DNA synthesis and maintenance and for the generation of new red blood cells. Cellular trafficking of FA and folate is based on its high-affinity binding to cognate folate receptor, a protein commonly expressed in several human cancers. Thus, folate conjugates of drugs, plasmids, biosensors, contrast, and radiodiagnostic imaging agents have been used for assisted delivery in folate receptor-positive cancer cells, via endocytosis pathways. This report describes morphologies of soft structures from a fully characterized FA-dipeptide conjugate and detailed mechanistic studies of its cancer cell uptake, as tracked by the inherent fluorescence of the conjugate. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd. PMID:25645907

Kaur, Gagandeep; Shukla, Akansha; Sivakumar, Sri; Verma, Sandeep

2015-03-01

168

Folic acid supplementation in pregnancy and implications in health and disease  

PubMed Central

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

2014-01-01

169

Folic acid attenuates cognitive dysfunction in streptozotocin-induced diabetic rats  

PubMed Central

Diabetic cognitive dysfunction is common in patients with diabetes but its pathogenesis is not clear. The aim of the present study is to investigate the role of 5’, 10’ methylene tetrahydrofolate reductase (MTHFR) in the development of diabetic cognitive impairment and test whether folic acid (FA) supplementation prevents cognitive dysfunction in diabetic rats. In the current study, three months after streptozotocin-induced diabetes onset, rats showed cognitive dysfunction including the prolonged escape latency, the decreased time spent in the target quadrant and the declined number of crossing the platform in Morris water maze test. Diabetic rats also presented elevated plasma homocysteine level and downregulation of MTHFR in hippocampus revealed by Western blotting. The diabetic cognitive dysfunction was attenuated by 30-day dietary FA treatment with a significantly decreased homocysteine level. In conclusion, these results suggest that MTHFR plays a crucial role in diabetic cognitive dysfunction and folate fortification might become a potent therapeutic strategy against diabetic cognitive impairment. PMID:25550933

Yang, Rui; Chen, Rong-Ping; Chen, Hong; Zhang, Hua; Cai, De-Hong

2014-01-01

170

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

PubMed

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

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

2014-03-12

171

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

PubMed

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

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

2015-03-01

172

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

PubMed

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

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

2013-12-01

173

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

PubMed

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

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

2014-04-01

174

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

Microsoft Academic Search

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

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

2008-01-01

175

[6S]5-methyltetrahydrofolate or folic acid supplementation and absorption and initial elimination of folate in young and middle-aged adults  

Microsoft Academic Search

Objectives:To assess the effects of supplementation with the diastereoisomer of 5-methyltetrahydrofolate ([6S]5-methylTHF), as an alternative supplement for folic acid, on folate absorption and elimination, in two age groups.Design:A randomized, double-blind intervention study.Subjects:A total of 12 young (<30 y) and 12 middle-aged (?50 y) healthy volunteers were recruited.Methods:Volunteers were randomized to receive daily supplementation with 400 ?g folic acid or equimolar

Meer van der K; Y. M. Smulders; J. R. Dainty; D E C Smith; R. M. Kok; C. D. A. Stehouwer; P. M. Finglas; C. A. J. M. Jakobs; K de Meer

2005-01-01

176

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

PubMed Central

BACKGROUND Folic acid intake during pregnancy can reduce the risk of neural tube defects (NTDs) and perhaps also oral facial clefts. Maternal autoantibodies to folate receptors can impair folic acid binding. We explored the relationship of these birth defects to inhibition of folic acid binding to folate receptor ? (FR?), as well as possible effects of parental demographics or prenatal exposures. METHODS We conducted a nested case–control study within the Norwegian Mother and Child Cohort Study. The study included mothers of children with an NTD (n= 11), cleft lip with or without cleft palate (CL/P, n= 72), or cleft palate only (CPO, n= 27), and randomly selected mothers of controls (n= 221). The inhibition of folic acid binding to FR? was measured in maternal plasma collected around 17 weeks of gestation. On the basis of prior literature, the maternal age, gravidity, education, smoking, periconception folic acid supplement use and milk consumption were considered as potential confounding factors. RESULTS There was an increased risk of NTDs with increased binding inhibition [adjusted odds ratio (aOR) = 1.4, 95% confidence interval (CI) 1.0–1.8]. There was no increased risk of oral facial clefts from inhibited folic acid binding to FR? (CL/P aOR = 0.7, 95% CI 0.6–1.0; CPO aOR = 1.1, 95% CI 0.8–1.4). No association was seen between smoking, folate supplementation or other cofactors and inhibition of folic acid binding to FR?. CONCLUSIONS Inhibition of folic acid binding to FR? in maternal plasma collected during pregnancy was associated with increased risk of NTDs but not oral facial clefts. PMID:21576080

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

2011-01-01

177

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

NASA Astrophysics Data System (ADS)

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.

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

2014-07-01

178

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

PubMed Central

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

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

2013-01-01

179

Use of multivitamins, folic acid and herbal supplements among breast cancer survivors: the black women's health study  

Microsoft Academic Search

Background  Complementary and alternative medicine (CAM) use, including herbals and multivitamin supplements, is quite common in the U.S.,\\u000a and has been shown to be highest in breast cancer survivors. However, limited data are currently available for CAM usage among\\u000a African Americans. Thus, we sought to determine the prevalence of multivitamins, folic acid and herbal supplement usage in\\u000a African American breast cancer

Mireille Bright-Gbebry; Kepher H Makambi; JoyAnn Phillips Rohan; Adana A Llanos; Lynn Rosenberg; Julie R Palmer; Lucile L Adams-Campbell

2011-01-01

180

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

NASA Astrophysics Data System (ADS)

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 ?A 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.

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

2012-08-01

181

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

PubMed Central

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

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

2013-01-01

182

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

PubMed

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

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

2015-04-01

183

Targeted delivery of Doxorubicin by folic acid-decorated dual functional nanocarrier.  

PubMed

Doxorubicin (DOX) is one of the most commonly used antineoplastic agents, but its clinical application is oftentimes coupled with severe side effects. Selective delivery of DOX to tumors via nanosized drug carrier represents an attractive approach to this problem. Previously, we developed a dual functional nanomicellar carrier, PEG5K-embelin2 (PEG5K-EB2), which was able to deliver paclitaxel (PTX) selectively to tumors and to achieve an enhanced therapeutic effect. In the present study, we examined the utility of PEG5K-EB2 to deliver DOX to tumors. In addition, folic acid (FA) was coupled to the surface of the PEG5K-EB2 micelles (FA-PEG5K-EB2) to further improve the selective targetability of the system. DOX-loaded PEG5K-EB2 micelles were uniformly spherical particles with a diameter of approximately 20 nm. Incorporation of FA had minimal effect on the size of the particles. The DOX loading efficiency was as high as 91.7% and 93.5% for PEG5K-EB2 and FA-PEG5K-EB2, respectively. DOX formulated in PEG5K-EB2 micelles (with or without FA decoration) demonstrated sustained kinetics of DOX release compared to free DOX. FA-PEG5K-EB2 significantly facilitated the intracellular uptake of DOX over free DOX and PEGylated liposomal DOX (Doxil) in breast cancer cells, 4T1.2, and drug resistant cells, NCI/ADR-RES. P-gp ATPase assay showed that PEG5K-EB2 significantly inhibited the function of the P-gp efflux pump. The maximum tolerated dose of DOX-loaded PEG5K-EB2 micelles was 15 mg/kg in mice, which was 1.5-fold greater than that for free DOX. Pharmacokinetics (PK) and biodistribution studies showed that both types of DOX-loaded micelles, especially FA-PEG5K-EB2, were able to significantly prolong the blood circulation time of DOX and facilitate its preferential accumulation at the tumor tissue. Finally, DOX/PEG5K-EB2 mixed micelles demonstrated significantly enhanced tumor growth inhibitory effect with minimal toxicity in comparison to free DOX and Doxil and the antitumor activity was further enhanced after the decoration by folic acid. Our data suggest that FA-PEG5K-EB2 micelles represent a promising DOX delivery system that warrants more study in the future. PMID:25265550

Lu, Jianqin; Zhao, Wenchen; Huang, Yixian; Liu, Hao; Marquez, Rebecca; Gibbs, Robert B; Li, Jiang; Venkataramanan, Raman; Xu, Liang; Li, Shulin; Li, Song

2014-11-01

184

Neuroprotective Effects of Glutamate Antagonists and Extracellular Acidity  

NASA Astrophysics Data System (ADS)

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 ?-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.

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

1993-06-01

185

Bioinformatic analysis of endothelial progenitor cells exposed to folic acid in type 1 diabetes mellitus.  

PubMed

We investigated the effects of type 1 diabetes mellitus (T1DM) on endothelial progenitor cells (EPCs) at the molecular level and assessed the therapeutic potential of folic acid (FA) in DM. We downloaded the gene expression profile of the EPCs from T1DM patients before and after treatment with FA and from healthy controls. We identified the differentially expressed genes (DEGs) in the EPCs from T1DM patients before and after a four-week period of FA treatment and compared them with those obtained from the healthy subjects by using limma package in R language. Then, functional annotation of the DEGs was performed using the online tool Database for Annotation, Visualization and Integrated Discovery (DAVID) based on the Kyoto Encyclopedia of Genes and Genomes database. The expression of 696 genes was altered in the EPCs from T1DM patients compared to those from the healthy controls. These genes were mainly involved in the pathways associated with immune response. FA can normalize majority of the altered gene expression profiles of EPCs from T1DM patients to resemble those of healthy subjects, albeit with some side effects. FA can be a potential therapeutic agent for the treatment of T1DM. However, focused efforts are required to ensure that the dose of FA falls within the permissible pharmacological range. PMID:24421150

Fang, D N; He, X D; Li, X H; Jia, H; Li, P Y; Lu, Q; Quan, Z; Wang, Q L

2014-01-01

186

Folic Acid-conjugated europium complexes as luminescent probes for selective targeting of cancer cells.  

PubMed

We report the synthesis of three optical probes (Eu(3+)?1, Eu(3+)?2, and Eu(3+)?3) having a luminescent Eu complex (signaling unit) bonded in different positions to folic acid (FA), the folate receptor (FR) targeting unit. The structures of the two regioisomers Eu(3+)?1 and Eu(3+)?2 were assigned by mass spectrometric experiments. The optical properties and stability of these probes were assessed in phosphate-buffered saline, cell culture medium, rat serum, and cellular lysate, and results indicated that they are chemically and photophysically stable. Cytotoxicity was studied with ovarian cancer cells having high (SKOV-3), intermediate (OVCAR-3), low (IGROV-1), or null (A2780) expression of FRs. The internalized probe, evaluated in SKOV-3, IGROV-1, and A2780 cells, was in the order Eu(3+)?2 > Eu(3+)?1 > Eu(3+)?3. No internalization was observed for A2780 cells. Such results, together with those obtained in competition experiments of FA versus Eu(3+)?2 and FA or Eu(3+)?2 versus (3)H-FA, indicate that internalization is receptor-mediated and that Eu(3+)?2 shows high selectivity and specificity for FR. PMID:25602505

Quici, Silvio; Casoni, Alessandro; Foschi, Francesca; Armelao, Lidia; Bottaro, Gregorio; Seraglia, Roberta; Bolzati, Cristina; Salvarese, Nicola; Carpanese, Debora; Rosato, Antonio

2015-02-26

187

Estimation of dietary folic acid intake in three generations of females in Southern Spain.  

PubMed

An adequate folic acid intake has been related to female fertility. The recommended intake of this vitamin was recently increased to 400?g/day, with an additional 200?g/day during pregnancy. The Mediterranean Diet includes sources of folate such as pulses, green-leaf vegetables, fruit, cereals, and dried fruits; other foods of interest are liver and blue fish. The objectives were to determine the foods that contribute most to folate intake and analyze the factors that influence their consumption by three generations in a female population (n=898; age, 10-75yrs) from Southern Spain: 230 adolescents (10-16yrs), 296 healthy pregnant women (19-45yrs), and 372 menopausal women (>45yrs). Participants completed a previously validated semi-quantitative food frequency questionnaire. Over 90% of their folate intake was supplied by cereals, fruit, natural juice, pulses, and cooked and raw vegetables. The mean (SD) daily intake of folate was 288.27(63.64) ?g. A higher Mediterranean Diet Score (MDS) was significantly related to a greater folate intake. The daily folate intake was not significantly influenced by educational level, number of children, or place of residence (rural vs. urban). In logistic regression analysis, the factors related to an adequate folate intake (>2/3 of recommendations) were higher age, higher MDS, and lower BMI. PMID:23587520

Monteagudo, C; Mariscal-Arcas, M; Palacin, A; Lopez, M; Lorenzo, M L; Olea-Serrano, F

2013-08-01

188

Folic acid-functionalized human serum albumin nanocapsules for targeted drug delivery to chronically activated macrophages.  

PubMed

Activated synovial macrophages play a key role in Rheumatoid Arthritis (RA). Recent studies have shown that folate receptor beta (FR?) is specifically expressed by activated macrophages. Therefore a folate-based nanodevice would provide the possibility of delivering therapeutic agents to activated macrophages without affecting normal cells and tissues. This study shows for the first time the sonochemical preparation of HSA nanocapsules avoiding toxic cross linking chemicals and emulsifiers used in other methods. Production of HSA nanocapsules was optimized leading to a diameter of 443.5 ± 9.0 nm and a narrow size distribution indicated by a polydispersity index (PDI) of 0.066 ± 0.080. Nanocapsules were surface modified with folic acid (FA) and the FA content was determined to be 0.38 and 6.42 molecules FA per molecule HSA, depending on the surplus of FA employed. Dynamic light scattering was used to determine size, PDI and zetapotential of the produced nanocapsules before and after surface modification. FA distribution on the surface of HSA nanocapsules was localized three-dimensionally after fluorescence labeling using confocal laser scanning microscopy (CLSM). Furthermore, specific binding and internalization of HSA nanocapsules by FR?-positive and FR?-negative macrophages, obtained from human peripheral blood mononuclear cells, was demonstrated by flow cytometry. FR?-expressing macrophages showed an increased binding for FA-modified capsules compared with those without FA. PMID:22374516

Rollett, Alexandra; Reiter, Tamara; Nogueira, Patricia; Cardinale, Massimiliano; Loureiro, Ana; Gomes, Andreia; Cavaco-Paulo, Artur; Moreira, Alexandra; Carmo, Alexandre M; Guebitz, Georg M

2012-05-10

189

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

PubMed Central

Over the last four decades, abnormalities in the methionine-homocysteine cycle and associated folate metabolism have garnered great interest due to the reported link between hyperhomocysteinemia and human pathology, especially atherothrombotic cardiovascular disease. However, clinical trials of B-vitamin supplementation including high doses of folic acid have not demonstrated any benefit in preventing or treating cardiovascular disease. In addition to the fact that these clinical trials may have been shorter in duration than appropriate for modulating chronic disease states, it is likely that reduction of the blood homocysteine level may be an oversimplified approach to a complex biologic perturbation. The methionine-homocysteine cycle and folate metabolism regulate redox and methylation reactions and are, in turn, regulated by redox and methylation status. Under normal conditions, a normal redox-methylation balance, or “methoxistasis”, exists, coordinated by the methionine-homocysteine cycle. An abnormal homocysteine level seen in pathologic states may reflect a disturbance of methoxistasis. We propose that future research should be targeted at estimating the deviation from methoxistasis and how best to restore it. This approach could lead to significant advances in preventing and treating cardiovascular diseases, including heart failure. PMID:23955381

Joseph, Jacob; Loscalzo, Joseph

2013-01-01

190

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

PubMed Central

The aim of the present study was to conduct an updated meta-analysis of relevant randomized controlled trials (RCTs) in order to estimate the effect of folic acid supplementation on endothelial function and the concentration of plasma homocysteine in patients with coronary artery disease (CAD). An extensive search of PubMed was conducted to identify RCTs that compared folic acid with placebo therapy. The mean difference (MD) and 95% confidence interval (CI) were used as a measure of the correlation between folic acid supplementation and endothelial function/plasma homocysteine concentration. Of the 377 patients included in this analysis, 191 patients underwent folic acid supplementation and 186 individuals underwent placebo treatment. Compared with the use of a placebo, folic acid supplementation alone exhibited significant efficacy on increasing flow-mediated dilation (FMD; MD, 57.72 ?m; 95% CI, 50.14–65.31; P<0.05) and lowering the concentration of plasma homocysteine (MD, ?3.66 ?mol/l; 95% CI, ?5.44–?1.87; P<0.05; I2, 87%). There was no significant change in the response to end diastolic diameter, glyceryl-trinitrate diameter, heart rate, baseline and peak hyperemic flow and systolic and diastolic blood pressure between the folic acid and placebo groups (P>0.05). Therefore, the meta-analysis indicated that 5 mg folic acid daily supplementation for >4 weeks significantly improved FMD and lowered the concentration of plasma homocysteine in patients with CAD. However, more RCTs are required in order to confirm these observations. PMID:24940394

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

2014-01-01

191

[Hematologic changes in patients under long-term hemodialysis and hemofiltration treatment with special reference to serum concentrations of folic acid and vitamin B 12].  

PubMed

The incidence of macrocytic anemia has been investigated in 32 patients on maintenance hemodialysis (mean age 46 years, mean duration of dialysis treatment 27.5 months), in 18 patients with combined hemodialysis (HD) and hemofiltration (HF) treatment (mean age 42 years, mean duration of combined HD and HF treatment 6.3 months) and in 32 patients after renal transplantation (mean age 41 years, mean observation period since successful renal transplantation 55.2 months). Also investigated were serum levels of vitamin B12 (radioassay kit 57Co) and folic acid (radioassay kit 125J). Macrocytosis (MCV greater than 96 fl) was observed in 38% of the patients on maintenance hemodialysis, in 44% of the patients with combined HD and HF treatment, and in 47% of the renal transplant recipients. In the chronically dialysed patients, in contrast to the patients with combined HD and HF treatment, the mean serum folic acid level was significantly lower (p less than 0.005) than that of healthy controls. Serum levels of vitamin B12 were within the normal range in all patients. There were no significant differences in serum levels of folic acid and vitamin B12 between the patients with MCV greater than 96 fl and MCV less than or equal to 96 fl. Nor was there a correlation between the serum levels of folic acid or vitamin B12 and mean corpuscular volume. These results suggest that folic acid deficiency is of minor importance in the complex pathogenesis of anemia in hemodialysed patients. PMID:6367027

Minar, E; Zazgornik, J; Bayer, P M; Lanschützer, H; Mengele, K; Marosi, L

1984-01-14

192

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

PubMed

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

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

2013-04-01

193

Ion-transfer voltammetric determination of folic acid at meso-liquid-liquid interface arrays.  

PubMed

Voltammetric studies on the simple ion transfer (IT) behaviors of an important water-soluble B-vitamin, folic acid (FA), at the liquid-liquid (L-L) interface were firstly performed and then applied as a novel detection method for FA under physiological conditions. Meso-water-1,6-dichlorohexane (W-DCH) and meso-water-organogel interface arrays were built by using a hybrid mesoporous silica membrane (HMSM) with a unique structure of pores-in-pores and employed as the new platforms for the IT voltammetric study. In view of the unique structure of the HMSM, the impact of the ionic surfactant cetyltrimethylammonium bromide (CTAB), self-assembled within the silica nanochannels of the HMSM, was investigated. In particular, its effect on the IT voltammetric behavior and detection of FA at meso-L-L interface arrays was systematically examined by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and differential pulse stripping voltammetry (DPSV). It was found that all the voltammetric responses of CV, DPV, and DPSV and the corresponding detection limit of FA at such meso-L-L interface arrays are closely related to the CTAB in the HMSM. Significantly, the calculated detection limit of FA could be improved to 80 nM after the combination of the DPSV technique with the additional preconcentration of FA in the silica-CTAB nanochannels, achieved through an anion-exchange process between FA(-) and the bromide of CTAB in HMSM. This provides a new and attractive strategy for the detection of those biological anions. PMID:25730302

Jiang, Xuheng; Gao, Kui; Hu, Daopan; Wang, Huanhuan; Bian, Shujuan; Chen, Yong

2015-04-21

194

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

PubMed Central

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

Lawal, Taiwo Akeem; Adeleye, Amos Olufemi

2014-01-01

195

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

PubMed Central

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

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

2013-01-01

196

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

PubMed

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

Sun, Conroy; Sze, Raymond; Zhang, Miqin

2006-09-01

197

Effect of narrowband ultraviolet B phototherapy on serum folic acid levels in patients with psoriasis.  

PubMed

Narrowband ultraviolet B phototherapy (NB-UVB) is a widely used modality in the treatment of psoriasis and is generally accepted as safe in pregnancy. Previous studies have described photodegradation of serum folate after exposure to UVA radiation but the effect of UVB is not known. We studied the effect of NB-UVB phototherapy on serum folic acid levels in patients with psoriasis and the relationship between changes in serum folate levels and the total cumulative dose of NB-UVB. Included in the study were 30 psoriatic patients between 13 and 55 years of age. Serum folate levels were measured at baseline, and after exposure to 18 and 36 sessions of NB-UVB irradiation. There were significant decreases in mean serum folate levels after NB-UVB exposure. After exposure to 18 and 36 sessions the decreases were 19% and 27%, respectively. After 18 sessions, the mean serum folate level had decreased in 18 patients (60%) from 8.64 ng/ml at baseline to 7.02 ng/ml (mean NB-UVB cumulative dose 40.02 J/cm(2); P?=?0.019). After 36 sessions, the mean serum folate levels had decreased in 22 patients (73%) to 6.32 ng/ml (mean NB-UVB cumulative dose 118.16 J/cm(2); P?=?0.002). The present study showed that high cumulative NB-UVB doses can induce folate photodegradation and decrease serum folate levels in patients with psoriasis and that this effect is directly related to the total cumulative dose of NB-UVB. PMID:21344249

El-Saie, Lotfy Taha; Rabie, Ali Ramadan; Kamel, Mohammed Ismail; Seddeik, Ahmad Kamel; Elsaie, Mohamed L

2011-07-01

198

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

PubMed Central

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

2014-01-01

199

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

Microsoft Academic Search

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

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

2011-01-01

200

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

PubMed Central

Background A novel dual ligand–modified liposome, folic acid-tethered Pep-1 peptide-conjugated liposomal nanocarrier (FP-Lipo), was designed to overcome the nonselectivity of conventional penetrating peptide-tagged nanoparticulates and to provide the advantage of selective targeting of the folic acid receptor, which is frequently overexpressed on epithelial cancer cells. Methods FP-Lipo was prepared by a sequential process of formation of a maleimide-derivatized small unilamellar vesicle, postinsertion of distearoyl phosphatidyl ethanolamine-polyethylene glycol 2000–folate to the vesicle, and Pep-1 peptide conjugation via thiol-maleimide linkage. Conformational and physical characteristics of the FP-Lipo nanocarriers were investigated for the extent of Pep-1 peptide and folic acid on the surface, vesicle size, and zeta potential. In vitro cellular uptake behaviors of the novel carrier containing a fluorescein dextran isothiocyanate probe were examined by spectrophotometry or by confocal laser scanning microscopy. Results A novel nanocarrier bearing approximately 750 folate ligands and 100 penetrating peptides per vesicle was successfully prepared. The physical properties were as follows: 140 nm in size; 5 mV in zeta potential; less than 0.3 in polydispersity index. An in vitro cellular uptake study revealed that the FP-Lipo nanocarrier system exhibited more than twofold enhanced translocation into the folic acid receptor–positive HeLa cells compared with the single Pep-1 peptide–modified liposome. Meanwhile, its cellular association and internalization into the folic acid receptor–negative normal HaCaT cells was comparable with that of Pep-1 peptide–modified liposome. Conclusion An advanced dual ligand-modified liposome is potentially useful for the treatment of folic acid receptor–positive tumors with high translocation capability of the penetrating peptide–modified liposome. PMID:23515421

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

2013-01-01

201

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

PubMed Central

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

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

2014-01-01

202

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

PubMed

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

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

2015-02-01

203

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

SciTech Connect

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

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

1990-02-26

204

Baseline Characteristics of Participants in the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial  

PubMed Central

Background Hyperhomocysteinemia may be a modifiable risk factor for the prevention of arteriosclerotic outcomes in chronic kidney disease (CKD). Few clinical trials of homocysteine lowering have been conducted in persons with CKD prior to reaching end-stage renal disease. Kidney transplant recipients are considered individuals with CKD. Objectives To describe the baseline characteristics of renal transplant recipients (RTRs) enrolled in a clinical trial of homocyteine lowering with a standard multivitamin containing high doses of folic acid, vitamins B6 and B12 aimed at reducing arteriosclerotic outcomes. Factors considered were level of kidney function, total homocysteine (tHcy) concentrations, and the prevalence of diabetes and previous cardiovascular disease (CVD). Study Design Cross sectional survey within a randomized controlled trial (RCT) cohort. Setting and Participants Participants were recruited from kidney transplant clinics in the U.S., Canada, and Brazil. Eligible participants had elevated levels of homocysteine (?12.0 ?mol/L in men and ?11.0 ?mol/L in women) and kidney function measured by Cockroft Gault estimated creatinine clearance of 30 mL/min or greater. Results Among 4,110 randomized participants 38.9% had diabetes, and 19.5% had previous CVD. Mean (± standard deviation) tHcy concentrations were 17.1 ± 6.3 ?mol/L, while the mean (± standard deviation) creatinine clearance was 66.4 ± 23.2 mL/min. Approximately 90% of the trial cohort had an estimated glomerular filtration rate (eGFR) consistent with stage 2-3 CKD (i.e., eGFR 30-89 mL/min). Limitations Analysis is based on cross-sectional data from a RCT, self-report of co-morbid illnesses, and level of kidney function was estimated. Conclusions A large population of stable RTRs who are at high risk for the development of CVD (both de novo and recurrent) has been recruited into FAVORIT and are likely to experience a sufficient number of events to address the primary hypothesis of the trial. PMID:19022547

Bostom, Andrew G.; Carpenter, Myra A.; Hunsicker, Lawrence; Jacques, Paul F.; Kusek, John W.; Levey, Andrew S.; McKenney, Joyce L.; Mercier, Renee Y.; Pfeffer, Marc A.; Selhub, Jacob

2009-01-01

205

Acetylation of p-aminobenzoylglutamate, a folic acid catabolite, by recombinant human arylamine N-acetyltransferase and U937 cells.  

PubMed Central

N-acetyl-p-aminobenzoylglutamate is a major urinary metabolite of folic acid. It is formed by acetylation of p-aminobenzoylglutamate following cleavage of the C9-N10 bond of folic acid. Using recombinant human type 1 (NAT1) and type 2 (NAT2) arylamine N-acetyltransferase, we have shown that p-aminobenzoylglutamate is a specific NAT1 substrate. At an acetyl-CoA concentration of 50 microM, the Km for p-aminobenzoylglutamate (pABG) acetylation by recombinant NAT1 was 130 +/- 13 microM. For the human pro-monocytic cell-line U937, the apparent Km was slightly higher (333 +/- 17 microM). Inhibitor studies supported NAT1-dependent acetylation of pABG by U937 cell cytosols. These studies are the first to identify a potential endogenous substrate for human NAT1 and suggest that this enzyme may be important in the cellular clearance of pABG. PMID:7717963

Minchin, R F

1995-01-01

206

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

PubMed Central

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

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

2014-01-01

207

A novel folic acid-conjugated TiO?-SiO? photosensitizer for cancer targeting in photodynamic therapy.  

PubMed

In this paper, a novel folic acid-conjugated silica-coated titanium dioxide (TiO2-SiO2) photosensitizer was synthesized and characterized using various analytical instruments. The photosensitizer was further assessed with regards to its photoreactivity, cellular and hemocompatibility, cell internalization, and phototoxicity. Conjugating folic acid with TiO2-SiO2 has shown a significantly improved compatibility of the nanoparticles with the mouse fibroblast cells (L929) at 24 h. An improved compatibility with the human nasopharyngeal epidermoid cancer (KB) cells was also demonstrated, but to a slightly reduced degree. Enhanced cell internalization was well demonstrated in the TiO2-SiO2 folate nanoparticles. Upon exposure to UV light, TiO2-SiO2 folate nanoparticles maintained a high level photodynamic reactivity and yielded a 38-43% photo-killing of KB cells. The photo-killing effect increased with increasing dosage in the investigated concentration range of 50-100 ?g ml(-1). PMID:25497292

Feng, Xiaohui; Zhang, Shaokun; Wu, Hong; Lou, Xia

2015-01-01

208

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

Microsoft Academic Search

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

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

1999-01-01

209

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...

210

Effect of niacin and folic acid in feed rations on growth and live weights of Green catfish (Mystus nemurus Valenciennes 1840).  

PubMed

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

Hien, D V; Doolgindachbaporn, S

2011-01-01

211

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...

212

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...

213

The Role of Zinc and Iron-Folic Acid Supplementation on Early Child Temperament and Eating Behaviors in Rural Nepal: A Randomized Controlled Trial  

PubMed Central

Child eating behaviors play an important role in nutrient intake, ultimately affecting child growth and later outcomes in adulthood. The study assessed the effects of iron-folic acid and zinc supplementation on child temperament and child eating behaviors in rural Nepal. Children (N = 569) aged 4–17 months in Sarlahi district, southern Nepal were randomized to receive daily supplements of placebo, iron-folic acid, zinc, or zinc plus iron-folic acid and followed for approximately 1 year. At baseline and four follow-up visits mothers completed questionnaires including information on demographic characteristics and child temperament and eating behaviors. The main effects of zinc and iron-folic acid supplementation on temperament and eating behaviors were assessed through crude and adjusted differences in mean cumulative score changes between visits 1 and 5. The adjusted rate-of-change for these outcomes was modeled using generalized estimating equations. Mean changes in temperament scores and in eating behavior scores between visits 1 and 5 were not significant in either the zinc or non-zinc group. Children in the iron-folic acid group increased temperament scores by 0.37 points over 5 visits (95% CI 0.02, 0.7), which was not significant after adjustment. Neither the adjusted rate-of-change in temperament scores between zinc and non-zinc (? = ?0.03, 95% CI ?0.3, 0.2) or iron-folic acid and non-iron-folic acid (? = 0.08, 95% CI ?0.2, 0.3) were significantly different. Adjusted rate of change analysis showed no significant difference between zinc and non-zinc (? = ?0.14, 95% CI ?0.3, 0.04) or between iron and non-iron eating behavior scores (? = ?0.11, 95% CI ?0.3, 0.1). Only among children with iron-deficiency anemia at baseline was there a significant decrease in eating behavior score, indicating better eating behaviors, when supplemented with zinc (? = ?0.3, 95% CI ?0.6, ?0.01), Ultimately, this effect of zinc on eating behaviors was the only effect we observed after approximately one year of micronutrient supplementation. Trial Registration ClinicalTrials.gov NCT00109551 PMID:25821959

Surkan, Pamela J.; Charles, Mary Katherine; Katz, Joanne; Siegel, Emily H.; Khatry, Subarna K.; LeClerq, Steven C.; Stoltzfus, Rebecca J.; Tielsch, James M.

2015-01-01

214

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

PubMed Central

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

Morse, Nancy L.

2012-01-01

215

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

PubMed

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

Kovaleva, V I; Bagatskaia, N V

2013-01-01

216

Photodynamic therapy effect of zinc monoamino phthalocyanine-folic acid conjugate adsorbed on single walled carbon nanotubes on melanoma cells.  

PubMed

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/cm(2) at 5 J/cm(2) 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. PMID:25305603

Ogbodu, Racheal O; Ndhundhuma, Ivy; Karsten, Aletta; Nyokong, Tebello

2015-02-25

217

Photodynamic therapy effect of zinc monoamino phthalocyanine-folic acid conjugate adsorbed on single walled carbon nanotubes on melanoma cells  

NASA Astrophysics Data System (ADS)

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.

Ogbodu, Racheal O.; Ndhundhuma, Ivy; Karsten, Aletta; Nyokong, Tebello

2015-02-01

218

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

PubMed

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

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

2015-03-01

219

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

PubMed Central

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

2013-01-01

220

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

PubMed Central

Background Hookworm infections are significant public health issues in South-East Asia. In women of reproductive age, chronic hookworm infections cause iron deficiency anaemia, which, upon pregnancy, can lead to intrauterine growth restriction and low birth weight. Low birth weight is an important risk factor for neonatal and infant mortality and morbidity. Methodology We investigated the association between neonatal birth weight and a 4-monthly deworming and weekly iron-folic acid supplementation program given to women of reproductive age in north-west Vietnam. The program was made available to all women of reproductive age (estimated 51,623) in two districts in Yen Bai Province for 20 months prior to commencement of birth weight data collection. Data were obtained for births at the district hospitals of the two intervention districts as well as from two control districts where women did not have access to the intervention, but had similar maternal and child health indicators and socio-economic backgrounds. The primary outcome was low birth weight. Principal Findings The birth weights of 463 infants born in district hospitals in the intervention (168) and control districts (295) were recorded. Twenty-six months after the program was started, the prevalence of low birth weight was 3% in intervention districts compared to 7.4% in control districts (adjusted odds ratio 0.29, 95% confidence interval 0.10 to 0.81, p?=?0.017). The mean birth weight was 124 g (CI 68 - 255 g, p<0.001) greater in the intervention districts compared to control districts. Conclusions/Significance The findings of this study suggest that providing women with regular deworming and weekly iron-folic acid supplements before pregnancy is associated with a reduced prevalence of low birth weight in rural Vietnam. The impact of this health system-integrated intervention on birth outcomes should be further evaluated through a more extensive randomised-controlled trial. PMID:22509421

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

2012-01-01

221

Neural tube defects in costa rica, 1987-2012: origins and development of birth defect surveillance and folic Acid fortification.  

PubMed

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

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

222

The Restrained Expression of NF-kB in Renal Tissue Ameliorates Folic Acid Induced Acute Kidney Injury in Mice  

PubMed Central

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

Kumar, Dev; Singla, Surinder K.; Puri, Veena; Puri, Sanjeev

2015-01-01

223

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

PubMed Central

Summary Introduction Iron deficiency is widespread in the developing world and is especially common in young children who live on the Indian subcontinent. Supplementation with iron and folic acid alleviates severe anaemia and enhances neurodevelopment in deficient populations, but little is known about the risks of mortality and morbidity associated with supplementation. Methods We did a community-based, cluster-randomised, double-masked, placebo-controlled, 2• 2 factorial trial in children aged 1?36 months and residing in southern Nepal. We randomly assigned children daily oral supplementation to age 36 months with: iron (12·5 mg) and folic acid (50 • g; n=8337), zinc alone (10 mg), iron, folic acid, and zinc (n=9230), or placebo (n=8683); children aged 1?11 months received half the dose. Our primary outcome measure was all-cause mortality, and our secondary outcome measures included cause-specific mortality and incidence and severity of diarrhoea, dysentery, and acute respiratory illness. Analyses were by intention to treat. This study is registered at clinicaltrials.gov, number NCT00109551. Findings The iron and folic acid-containing groups of the study were stopped early in November, 2003, on the recommendation of the data and safety monitoring board; mortality in these groups did not differ from placebo and there was low power to detect positive or negative effects by the time enrolment was completed. We continued to enrol children to the placebo and zinc alone groups. 25 490 children participated and analyses are based on 29 097·3 person-years of follow-up. There was no difference in mortality between the groups who took iron and folic acid without or with zinc when compared with placebo (HR 1·03, 95% CI 0·78?1·37, and 1·00, 0·74?1·34, respectively). There were no significant differences in the attack rates for diarrhoea, dysentery, or respiratory infections between groups, although all the relative risks except one indicated modest, non-significant protective effects. Interpretation Daily supplementation of young children in southern Nepal with iron and folic acid with or without zinc has no effect on their risk of death, but might protect against diarrhoea, dysentery, and acute respiratory illness. PMID:16413878

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

2008-01-01

224

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

PubMed

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

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

2014-03-25

225

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

PubMed

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

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

2014-03-01

226

Maternal exposure to fluoxetine during gestation and lactation affects the DNA methylation programming of rat's offspring: modulation by folic acid supplementation.  

PubMed

Fluoxetine is an antidepressant that has been largely used for treatment of depression in pregnancy. In the present study we evaluated the effects of the exposure to fluoxetine during gestation and lactation on DNA methylation of rat brain regions. Female Wistar rats were treated with 5mg/kg of fluoxetine during pregnancy and lactation. In order to assess the effects of fluoxetine in the context of maternal folic acid supplementation we performed an additional combined treatment composed by folic acid (8 mg/kg/day) and fluoxetine (5 mg/kg/day). On the postnatal day 22, male rats were euthanized and hippocampus, cortex, hypothalamus, and periaqueductal gray area were removed. Global DNA methylation was quantified using a high-throughput ELISA-based method. Neurofunctional changes were addressed using validated behavioral tests: hot plate, elevated plus maze and open field. A decrease in the global DNA methylation profile of hippocampus was associated to the exposure to fluoxetine, whereas an increase in methylation was observed in cortex. The combined treatment induced an increase in the methylation of hippocampus indicating the potential of folic acid to modulate this epigenetic alteration. Increase in the latency to the thermal nociceptive response was observed in animals exposed to fluoxetine whereas this effect was abolished in animals from the combined treatment. In summary we demonstrated that exposure to fluoxetine during gestation and lactation affect the DNA methylation of brain and the nociceptive response of rats. Furthermore our data reveal the potential of folic acid to modulate epigenetic and functional changes induced by early exposure to fluoxetine. PMID:24583191

Toffoli, L V; Rodrigues, G M; Oliveira, J F; Silva, A S; Moreira, E G; Pelosi, G G; Gomes, M V

2014-05-15

227

Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil-DNA glycosylase impair learning in a mouse model of vascular cognitive impairment.  

PubMed

Dietary deficiencies in folic acid result in elevated levels of plasma homocysteine, which has been associated with the development of dementia and other neurodegenerative disorders. Previously, we have shown that elevated levels of plasma homocysteine in mice deficient for a DNA repair enzyme, uracil-DNA glycosylase (UNG), result in neurodegeneration. The goal of this study was to evaluate how deficiencies in folic acid and UNG along with elevated levels of homocysteine affect vascular cognitive impairment, via chronic hypoperfursion in an animal model. Ung(+/+) and Ung(-/-) mice were placed on either control (CD) or folic acid deficient (FADD) diets. Six weeks later, the mice either underwent implantation of microcoils around both common carotid arteries. Post-operatively, behavioral tests began at 3-weeks, angiography was measured after 5-weeks using MRI to assess vasculature and at completion of study plasma and brain tissue was collected for analysis. Learning impairments in the Morris water maze (MWM) were observed only in hypoperfused Ung(-/-) FADD mice and these mice had significantly higher plasma homocysteine concentrations. Interestingly, Ung(+/+) FADD produced significant remodeling of the basilar artery and arterial vasculature. Increased expression of GFAP was observed in the dentate gyrus of Ung(-/-) hypoperfused and FADD sham mice. Chronic hypoperfusion resulted in increased cortical MMP-9 protein levels of FADD hypoperfused mice regardless of genotypes. These results suggest that elevated levels of homocysteine only, as a result of dietary folic acid deficiency, don't lead to memory impairments and neurobiochemical changes. Rather a combination of either chronic hypoperfusion or UNG deficiency is required. PMID:25655513

Jadavji, Nafisa M; Farr, Tracy D; Lips, Janet; Khalil, Ahmed A; Boehm-Sturm, Philipp; Foddis, Marco; Harms, Christoph; Füchtemeier, Martina; Dirnagl, Ulrich

2015-04-15

228

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)

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.

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

2014-03-01

229

Homocysteine, MTHFR C677T gene polymorphism, folic acid and vitamin B 12 in patients with retinal vein occlusion  

PubMed Central

Background Many available data have suggested that hyperhomocysteinaemia, an established independent risk factor for thrombosis (arterial and venous), may be associated with an increased risk of retinal vein occlusion (RVO). Aim of the study To evaluate homocysteine metabolism in consecutive caucasian patients affected by RVO from Northern Italy. Patients and Methods 69 consecutive patients from Northern Italy (mean age 64.1 ± 14.6 yy) with recent RVO, were tested for plasma levels of homocysteine (tHcy: fasting and after loading with methionine), cyanocobalamine and folic acid levels (CMIA-Abbot) and looking for MTHFR C677T mutation (Light Cycler-Roche) and compared to 50 volunteers, enrolled as a control group. Results Fasting levels of tHcy were significantly higher in patients than in controls: mean value 14.7 ± 7.7 vs 10.2 ± 8 nmol/ml. Post load levels were also significantly higher: mean value 42.7 ± 23.7 vs 30.4 ± 13.3 nmol/ml; Total homocysteine increase was also evaluated (i.e. ?-tHcy) after methionine load and was also significantly higher in patients compared to control subjects: mean ?-tHcy 27.8 ± 21.5 vs 21.0 ± 16 nmol/ml (normal value < 25 nmol/ml). Furthermore, patients affected by RVO show low folic acid and/or vitamin B12 levels, although differences with control group did not reach statistical significance. Heterozygous and homozygous MTHFR mutation were respectively in study group 46% and 29% vs control group 56% and 4%. Conclusion our data confirm that hyperhomocysteinaemia is a risk factor for RVO, and also that TT genotype of MTHFR C677T is more frequently associated with RVO: if the mutation per se is a risk factor for RVO remains an open question to be confirmed because another study from US did not reveal this aspect. Hyperomocysteinemia is modifiable risk factor for thrombotic diseases. Therefore, a screening for tHcy plasma levels in patients with recent retinal vein occlusion could allow to identify patients who might benefit from supplementation with vitamins and normalization of homocysteine levels, in fasting and after methionine load. PMID:16144556

Ferrazzi, Paola; Di Micco, Pierpaolo; Quaglia, Ilaria; Rossi, Lisa Simona; Bellatorre, Alessandro Giacco; Gaspari, Giorgio; Rota, Lidia Luciana; Lodigiani, Corrado

2005-01-01

230

Folic acid conjugated cross-linked acrylic polymer (FA-CLAP) hydrogel for site specific delivery of hydrophobic drugs to cancer cells  

PubMed Central

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

2014-01-01

231

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

PubMed Central

Background A critical disadvantage for successful chemotherapy with paclitaxel (PTX) is its nontargeting nature to cancer cells. Folic acid has been employed as a targeting ligand of various anticancer agents to increase their cellular uptake within target cells since the folate receptor is overexpressed on the surface of such tumor cells. In this study, a novel biodegradable deoxycholic acid-O-carboxymethylated chitosan–folic acid conjugate (DOMC-FA) was used to form micelles for encapsulating the anticancer drug PTX. Methods and results The drug-loading efficiency, encapsulation efficiency, in vitro drug release and physicochemical properties of PTX-loaded micelles were investigated in detail. In vitro cell culture studies were carried out in MCF-7 cells, a human breast carcinoma cell line, with folate receptor overexpressed on its surface. An increased level of uptake of folate-conjugated micelles compared to plain micelles in MCF-7 cells was observed, and the enhanced uptake of folate-micelles mainly on account of the effective process of folate receptor-mediated endocytosis. The MTT assay, morphological changes, and apoptosis test implied that the folate-conjugated micelles enhanced the cell death by folate-mediated active internalization, and the cytotoxicity of the FA-micellar PTX (DOMC-FA/PTX) to cancer cells was much higher than micelles without folate (DOMC/PTX) or the commercially available injectable preparation of PTX (Taxol). Conclusion Results indicate that the PTX-loaded DOMC-FA micelle is a successful anticancertargeted drug-delivery system for effective cancer chemotherapy. PMID:22287842

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

2012-01-01

232

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

PubMed

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

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

2013-01-01

233

Single-base resolution of mouse offspring brain methylome reveals epigenome modifications caused by gestational folic acid  

PubMed Central

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

2014-01-01

234

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

SciTech Connect

Apoptosis (APO) and necrosis (NEC) are two different types of cell death occurring in response to cellular stress factors. Cells with DNA damage may undergo APO or NEC. Folate is an essential micronutrient associated with DNA synthesis, repair and methylation. Methylenetetrahydrofolate reductase (MTHFR) regulates intracellular folate metabolism. Folate deficiency and MTHFR C677T polymorphisms have been shown to be related to DNA damage. To verify the cytotoxic effects of folate deficiency on cells with different MTHFR C677T genotypes, 15 human peripheral lymphocyte cases with different MTHFR C677T genotypes were cultured in folic acid (FA)-deficient and -sufficient media for 9 days. Cytotoxicity was quantified using the frequencies of APO and NEC as endpoints, the nuclear division index (NDI), and the number of viable cells (NVC). These results showed that FA is an important factor in reducing cytotoxicity and increasing cell proliferation. Lymphocytes with the TT genotype proliferated easily under stress and exhibited different responses to FA deficiency than lymphocytes with the CC and CT genotypes. A TT individual may accumulate more cytotoxicity under cytotoxic stress, suggesting that the effects of FA deficiency on cytotoxicity are greater than the effects in individuals with the other MTHFR C677T variants.

Wu Xiayu; Liang Ziqing [School of Life Sciences, Yunnan Normal University, Kunming Yunnan 650092 (China); Zou Tianning [Thirdary Affiliated hospital of Kunming Medical College, Kunming Yunnan 650101 (China); Wang Xu [School of Life Sciences, Yunnan Normal University, Kunming Yunnan 650092 (China)], E-mail: wangxu@fudan.edu.cn

2009-02-13

235

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

NASA Astrophysics Data System (ADS)

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

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

2013-04-01

236

Folic acid functionalized silver nanoparticles with sensitivity and selectivity colorimetric and fluorescent detection for Hg2+ and efficient catalysis.  

PubMed

In this research, folic acid functionalized silver nanoparticles (FA-AgNPs) were selected as a colorimetric and a 'turn on' fluorescent sensor for detecting Hg(2+). After being added into Hg(2+), AgNPs can emit stable fluorescence at 440 nm when the excitation wavelength is selected at 275 nm. The absorbance and fluorescence of the FA-AgNPs could reflect the concentration of the Hg(2+) ions. Thus, we developed a simple, sensitive analytical method to detect Hg(2+) based on the colorimetric and fluorescence enhancement of FA-AgNPs. The sensor exhibits two linear response ranges between absorbance and fluorescence intensity with Hg(2+) concentration, respectively. Meanwhile, a detection limit of 1 nM is estimated based on the linear relationship between responses with a concentration of Hg(2+). The high specificity of Hg(2+) with FA-AgNPs interactions provided the excellent selectivity towards detecting Hg(2+) over other metal ions (Pb(2+), Mg(2+), Zn(2+), Ni(2+), Cu(2+), Co(2+), Ca(2+), Mn(2+), Fe(2+), Cd(2+), Ba(2+), Cr(6+) and Cr(3+)). This will provide a simple, effective and multifunctional colorimetric and fluorescent sensor for on-site and real-time Hg(2+) ion detection. The proposed method can be applied to the analysis of trace Hg(2+) in lake water. Additionally, the FA-AgNPs can be used as efficient catalyst for the reduction of 4-nitrophenol and potassium hexacyanoferrate (III). PMID:25116278

Su, Dongyue; Yang, Xin; Xia, Qingdong; Zhang, Qi; Chai, Fang; Wang, Chungang; Qu, Fengyu

2014-09-01

237

Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD1 mice  

Microsoft Academic Search

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

Jennifer E. Dawson; Angela M. Raymond; Louise M.. Winn

2006-01-01

238

Intermediate states in the binding process of folic acid to folate receptor ?: insights by molecular dynamics and metadynamics.  

PubMed

Folate receptor ? (FR?) is a cell surface, glycophosphatidylinositol-anchored protein which has focussed attention as a therapeutic target and as a marker for the diagnosis of cancer. It has a high affinity for the dietary supplemented folic acid (FOL), carrying out endocytic transport across the cell membrane and delivering the folate at the acidic pH of the endosome. Starting from the recently reported X-ray structure at pH 7, 100 ns classical molecular dynamics simulations have been carried out on the FR?-FOL complex; moreover, the ligand dissociation process has been studied by metadynamics, a recently reported method for the analysis of free-energy surfaces (FES), providing clues on the intermediate states and their energy terms. Multiple dissociation runs were considered to enhance the configurational sampling; a final clustering of conformations within the averaged FES provides the representative structures of several intermediate states, within an overall barrier for ligand escape of about 75 kJ/mol. Escaping of FOL to solvent occurs while only minor changes affect the FR? conformation of the binding pocket. During dissociation, the FOL molecule translates and rotates around a turning point located in proximity of the receptor surface. FOL at this transition state assumes an "L" shaped conformation, with the pteridin ring oriented to optimize stacking within W102 and W140 residues, and the negatively charged glutamate tail, outside the receptor, interacting with the positively charged R103 and R106 residues, that contrary to the bound state, are solvent exposed. We show that metadynamics method can provide useful insights at the atomistic level on the effects of point-mutations affecting functionality, thus being a very promising tool for any study related to folate-targeted drug delivery or cancer therapies involving folate uptake. PMID:25323390

Della-Longa, Stefano; Arcovito, Alessandro

2015-01-01

239

Control of prostate cancer associated with withdrawal of a supplement containing folic acid, L-methyltetrahydrofolate and vitamin B12: a case report  

PubMed Central

Introduction This is the first report of possible direct stimulation of hormone-resistant prostate cancer or interference of docetaxel cytotoxicity of prostate cancer in a patient with biochemical relapse of prostatic-specific antigen. This observation is of clinical and metabolic importance, especially at a time when more than 80 countries have fortified food supplies with folic acid and some contemplate further fortification with vitamin B12. Case presentation Our patient is a 71-year-old Caucasian man who had been diagnosed in 1997 with prostate cancer, stage T1c, and Gleason score 3+4 = 7. His primary treatment included intermittent androgen deprivation therapy including leuprolide + bicalutamide + deutasteride, ketoconazole + hydrocortisone, nilandrone and flutamide to resistance defined as biochemical relapse of PSA. While undergoing docetaxel therapy to treat a continually increasing prostate-specific antigen level, withdrawal of 10 daily doses of a supplement containing 500 ?g of vitamin B12 as cyanocobalamin, as well as 400 ?g of folic acid as pteroylglutamic acid and 400 ?g of L-5-methyltetrahydrofolate for a combined total of 800 ?g of mixed folates, was associated with a return to a normal serum prostatic-specific antigen level. Conclusion This case report illustrates the importance of the effects of supplements containing large amounts of folic acid, L-5-methyltetrahydrofolate, and cyanocobalamin on the metabolism of prostate cancer cells directly and/or B vitamin interference with docetaxel efficacy. Physicians caring for patients with prostate cancer undergoing watchful waiting, hormone therapy, and/or chemotherapy should consider the possible acceleration of tumor growth and/or metastasis and the development of drug resistance associated with supplement ingestion. We describe several pathways of metabolic and epigenetic interactions that could affect the observed changes in serum levels of prostate-specific antigen. PMID:21867542

2011-01-01

240

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

SciTech Connect

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

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

1986-03-05

241

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

PubMed Central

We have reported that folic acid, vitamin B12, and omega-3 fatty acids are interlinked in the one carbon cycle and have implications for fetal programming. Our earlier studies demonstrate that an imbalance in maternal micronutrients influence long chain polyunsaturated fatty acid metabolism and global methylation in rat placenta. We hypothesize that these changes are mediated through micronutrient dependent regulation of enzymes in one carbon cycle. Pregnant dams were assigned to six dietary groups with varying folic acid and vitamin B12 levels. Vitamin B12 deficient groups were supplemented with omega-3 fatty acid. Placental mRNA levels of enzymes, levels of phospholipids, and glutathione were determined. Results suggest that maternal micronutrient imbalance (excess folic acid with vitamin B12 deficiency) leads to lower mRNA levels of methylene tetrahydrofolate reductase (MTHFR) and methionine synthase , but higher cystathionine b-synthase (CBS) and Phosphatidylethanolamine-N-methyltransferase (PEMT) as compared to control. Omega-3 supplementation normalized CBS and MTHFR mRNA levels. Increased placental phosphatidylethanolamine (PE), phosphatidylcholine (PC), in the same group was also observed. Our data suggests that adverse effects of a maternal micronutrient imbalanced diet may be due to differential regulation of key genes encoding enzymes in one carbon cycle and omega-3 supplementation may ameliorate most of these changes. PMID:25003120

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

2014-01-01

242

Size control in the synthesis of 1-6 nm gold nanoparticles using folic acid-chitosan conjugate as a stabilizer  

NASA Astrophysics Data System (ADS)

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.

Liu, Lili; Zhang, Xianwen; Chaudhuri, Jharna

2014-09-01

243

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

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

Warad, Shivaraj; Kalburgi, Nagaraj B; Kalburgi, Veena C; Koregol, Arati C; Patanashetti, Jyoti; Rao, Subramaniam; Kokatnur, M. Vijayalaxmi

2014-01-01

244

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

PubMed

Methotrexate (MTX) is an anti-metabolite widely used in the treatment of neoplastic disorders, rheumatoid arthritis and psoriasis. The basis for its therapeutic efficacy is the inhibition of dihydrofolate reductase (DHFR), a key enzyme in the folic acid (FA) metabolism. FA is a water-soluble vitamin which is involved in the synthesis of purines and pyrimidines, the essential precursors of DNA. Folinic acid (FNA) is the reduced form of FA that circumvents the inhibition of DHFR. Folate supplementation during MTX therapy for psoriasis and inflammatory arthritis reduces both toxicity and side effects without compromising the efficacy. Further, FNA supplementation reduces the common side effects of MTX in the treatment of juvenile idiopathic arthritis. FA and FNA are reported to have protective effects on MTX-induced genotoxicity in the somatic cells; however their protective effects on the germ cells have not been much explored. Previously, we evaluated the cytotoxic and genotoxic effects of MTX in the germ cells of mice. In the present study, we have intervened FA and FNA for the protection of germ cell toxicity induced by MTX in male swiss mice. The animals were pre-treated with FA at the doses of 50, 100 and 200 microg/kg for 4 consecutive days per week and on day five; MTX was administered at the dose of 20mg/kg once. FNA was administered at the doses of 2.5, 5 and 10 mg/kg, 6 h (h) after single administration of MTX at the dose of 20 mg/kg. The dosing regimen was continued up to 10 weeks. The germ cell toxicity was evaluated using testes weight (wt), sperm count, sperm head morphology, sperm comet assay, histology, TUNEL and halo assay in testis. The results clearly demonstrate that prior administration of FA and post-treatment with FNA reduces the germ cell toxicity induced by MTX as evident from the decreased sperm head abnormalities, seminiferous tubule damage, sperm DNA damage, TUNEL positive cells and increased sperm counts. In the present study, we report that FA and FNA ameliorate the germ cell toxicity of MTX in mice. PMID:19110071

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

2009-02-19

245

Combating Iron Deficiency Anemia among School Going Adolescent Girls in a Hilly State of North India: Effectiveness of Intermittent Versus Daily Administration of Iron Folic Acid Tablets  

PubMed Central

Background: National surveys in India have documented an increasing number of adolescent girls suffering from anemia. Efforts to build iron stores in adolescent girls will help them improve their prepregnancy hemoglobin level. To assess the effectiveness of school-based supervised weekly, bi–weekly, and daily regimen of iron folic tablets in the treatment of anemia among adolescent girls. Methods: This randomized clinical trial included 331 anemic school going adolescent girls of Shimla district of North India. Study subjects were randomized to once weekly, bi–weekly, and daily iron folic acid regimen group. An intent-to-treat approach was used to analyze the change in hemoglobin level and serum ferritin levels at the end of the trial period. Results: The rate of change of hemoglobin and serum ferritin levels from baseline to the end of the intervention was found to be similar in all the three groups (P = 0.64 and 0.98 for change in hemoglobin and serum ferritin). Bi-weekly treatment regimen results in comparatively more increase in hemoglobin levels (3.1 g/dl) as compared to once weekly (2.4 g/dl) and daily groups (2.3 g/dl) (ANOVA F statistics = 6.08, P = 0.003). Among the study subjects who reported side effects, more were from daily regimen group (55%) as compared to intermittent regimen group (25% in bi-weekly group; 18% in weekly group; P < 0.001). Conclusions: In Shimla hills of North India, school-based intermittent iron-folic acid therapy is a feasible and effective intervention for increasing hemoglobin and serum ferritin levels of anemic adolescent girls. PMID:25538845

Gupta, Anmol; Parashar, Anupam; Thakur, Anita; Sharma, Deepak; Bhardwaj, Parveen; Jaswal, Saroj

2014-01-01

246

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

PubMed

Data on the effect of combined genetic polymorphisms, involved in folate metabolism, on the concentration of serum folate after folic acid supplementation are scarce. Therefore, we investigated the impact of seven gene polymorphisms on the concentration of serum folate and p-tHcy in healthy subjects after short-term folic acid supplementation. In a randomized, double blind, crossover study, apparently healthy subjects were given either 0.8 mg folic acid per day (n = 46) or placebo (n = 45) for 14 days. The washout period was 14 days. Fasting blood samples were collected on day 1, 15, 30 and 45. Data on subjects on folic acid supplementation (n = 91) and on placebo (n = 45) were used for the statistical analysis. The concentration of serum folate increased higher in subjects with higher age (53.5 ± 7.0 years) than in subjects with lower age (24.3 ± 3.2 years) after folic acid supplementation (p = 0.006). The baseline concentration of serum folate in subjects with polymorphism combination, reduced folate carrier protein, RFC1-80 GA and methylenetetrahydrofolate reductase, MTHFR677 CT+TT, was lower than RFC1-80 AA and MTHFR677 CT+TT (p = 0.002). After folic acid supplementation, a higher increase in the concentration of serum folate was detected in subjects with polymorphism combination RFC1-80 GA and MTHFR677 CC than RFC1-80 GG and MTHFR CT+TT combination (p < 0.0001). The baseline concentration of plasma total homocysteine (p-tHcy) was altered by combined polymorphisms in genes associated with folate metabolism. After folic acid supplementation, in subjects with combined polymorphisms in methylenetetrahydrofolate dehydrogenase, MTHFD1-1958 and MTHFR-677 genes, the concentration of p-tHcy was changed (p = 0.002). The combination of RFC1-80 and MTHFR-677 polymorphisms had a profound affect on the concentration of serum folate in healthy subjects before and after folic acid supplementation. PMID:25758536

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

2015-05-01

247

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

PubMed Central

Background Studies have indicated that altered maternal micronutrients and vitamins influence the development of newborns and altered nutrient exposure throughout the lifetime may have potential health effects and increased susceptibility to chronic diseases. In recent years, folic acid (FA) exposure has significantly increased as a result of mandatory FA fortification and supplementation during pregnancy. Since FA modulates DNA methylation and affects gene expression, we investigated whether the amount of FA ingested during gestation alters gene expression in the newborn cerebral hemisphere, and if the increased exposure to FA during gestation and throughout the lifetime alters behavior in C57BL/6J mice. Methods Dams were fed FA either at 0.4 mg or 4 mg/kg diet throughout the pregnancy and the resulting pups were maintained on the diet throughout experimentation. Newborn pups brain cerebral hemispheres were used for microarray analysis. To confirm alteration of several genes, quantitative RT-PCR (qRT-PCR) and Western blot analyses were performed. In addition, various behavior assessments were conducted on neonatal and adult offspring. Results Results from microarray analysis suggest that the higher dose of FA supplementation during gestation alters the expression of a number of genes in the newborns’ cerebral hemispheres, including many involved in development. QRT-PCR confirmed alterations of nine genes including down-regulation of Cpn2, Htr4, Zfp353, Vgll2 and up-regulation of Xist, Nkx6-3, Leprel1, Nfix, Slc17a7. The alterations in the expression of Slc17a7 and Vgll2 were confirmed at the protein level. Pups exposed to the higher dose of FA exhibited increased ultrasonic vocalizations, greater anxiety-like behavior and hyperactivity. These findings suggest that although FA plays a significant role in mammalian cellular machinery, there may be a loss of benefit from higher amounts of FA. Unregulated high FA supplementation during pregnancy and throughout the life course may have lasting effects, with alterations in brain development resulting in changes in behavior. PMID:25006883

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

2014-01-01

248

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

PubMed Central

Background In most patients, acute kidney injury (AKI) represents the combined effects of ischemic, toxic and inflammatory insults. No effective pharmacologic interventions have been developed to prevent AKI or to improve outcomes to date. Cyclosporine A (CsA) is a calcineurin inhibitor that mediates T-cell receptor signaling, suppresses inflammatory cytokine expression and inhibits leukocyte migration. It is also a potent inhibitor of mitochondrial permeability, protecting cells from death. These properties make it a potentially valuable drug to prevent or treat AKI. It does, however, carry a significant risk of nephrotoxicity, especially with chronic use. By contrast, a single dose of CsA may be protective while limiting the risk of nephrotoxicity. Methods We conducted a controlled animal experiment in male CD-1 mice. Specifically, mice were subjected to folic acid (FA)-induced AKI and then randomly assigned to sham operation or one of three dosage of CsA treatment groups. Results Intraperitoneal injection of FA consistently induced AKI. Serum interleukin (IL)-6 and urinary neutrophil gelatinase-associated lipocalin (NGAL) rose 1 day after FA injection. Compared to sham treatment, one dose (1 and 5 mg/kg body weight) of CsA significantly reduced kidney tubular cell apoptosis, serum creatinine, blood urea, serum IL-6 and urinary NGAL 2 days after FA injection. It was also shown to block the inflammatory mediator tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) expression, nuclear factor kappa-B (NF?B) activation, inflammatory cell infiltration and interstitial fibrosis 14 days after treatment in a dose-dependent fashion. By contrast, a dose of 10 mg/kg body weight CsA resulted in nephrotoxicity in the setting of FA-induced AKI. Conclusions A single dose of CsA, currently used for organ transplant, significantly protects mice from FA-induced AKI, presumably through inhibition of cell death, inflammatory reaction, interstitial cell infiltration and fibrosis. The protective effects have the potential to open a completely new line of investigation in the prevention and treatment of AKI. PMID:22294776

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

2012-01-01

249

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

PubMed Central

Drug targeting is an active area of research and nano-scaled drug delivery systems hold tremendous potential for the treatment of neoplasms. In this study, a novel cyclodextrin (CD)-based nanoparticle drug delivery system has been assembled and characterized for the therapy of folate receptor-positive [FR(+)] cancer. Water-soluble folic acid (FA)-conjugated CD carriers (FACDs) were successfully synthesized and their structures were confirmed by 1D/2D nuclear magnetic resonance (NMR), matrix-assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS), high performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR), and circular dichroism. Drug complexes of adamatane (Ada) and cytotoxic doxorubicin (Dox) with FACD were readily obtained by mixed solvent precipitation. The average size of FACD-Ada-Dox was 1.5–2.5 nm. The host-guest association constant Ka was 1,639 M?1 as determined by induced circular dichroism and the hydrophilicity of the FACDs was greatly enhanced compared to unmodified CD. Cellular uptake and FR binding competitive experiments demonstrated an efficient and preferentially targeted delivery of Dox into FR-positive tumor cells and a sustained drug release profile was seen in vitro. The delivery of Dox into FR(+) cancer cells via endocytosis was observed by confocal microscopy and drug uptake of the targeted nanoparticles was 8-fold greater than that of non-targeted drug complexes. Our docking results suggest that FA, FACD and FACD-Ada-Dox could bind human hedgehog interacting protein that contains a FR domain. Mouse cardiomyocytes as well as fibroblast treated with FACD-Ada-Dox had significantly lower levels of reactive oxygen species, with increased content of glutathione and glutathione peroxidase activity, indicating a reduced potential for Dox-induced cardiotoxicity. These results indicate that the targeted drug complex possesses high drug association and sustained drug release properties with good biocompatibility and physiological stability. The novel FA-conjugated ?-CD based drug complex might be promising as an anti-tumor treatment for FR(+) cancer. PMID:23658721

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

250

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

PubMed

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

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

2008-01-01

251

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

PubMed Central

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

2014-01-01

252

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)

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.

Feng, Yu; Wang, Song; Chen, Runsen; Tong, Xing; Wu, Zeyu; Mo, Xuming

2015-02-01

253

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

NASA Astrophysics Data System (ADS)

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

Hwang, Sun-Young

254

Maternal Folic Acid Supplementation and the Risk of Congenital Heart Defects in Offspring: A Meta-Analysis of Epidemiological Observational Studies  

PubMed Central

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

Feng, Yu; Wang, Song; Chen, Runsen; Tong, Xing; Wu, Zeyu; Mo, Xuming

2015-01-01

255

Maternal folic Acid supplementation and the risk of congenital heart defects in offspring: a meta-analysis of epidemiological observational studies.  

PubMed

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, I(2) = 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

Feng, Yu; Wang, Song; Chen, Runsen; Tong, Xing; Wu, Zeyu; Mo, Xuming

2015-01-01

256

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...

257

Positive impact of a weekly iron-folic acid supplement delivered with social marketing to Cambodian women: compliance, participation, and hemoglobin levels increase with higher socioeconomic status.  

PubMed

A social marketing program promoting weekly iron-folic acid supplementation improved hemoglobin levels in women of reproductive age in Cambodia. Supplementation was increasingly effective among women of higher socioeconomic status (SES). Among higher SES schoolgirls, 58% took the supplements, compared with 49% for lower SES (P = 0.07). Garment factory workers with an 11th- or 12th-grade education had a mean improvement in hemoglobin of 0.72 g/dL over those with a 5th-grade education or less (P = 0.04). The percentage of rural village women taking supplements increased with increasing SES (linear trend P = 0.046). These results suggest that women with lower SES be given special attention for future programs. PMID:16466089

Crape, Byron L; Kenefick, Eric; Cavalli-Sforza, Tommaso; Busch-Hallen, Jennifer; Milani, Silvano; Kanal, Koum

2005-12-01

258

Weekly Iron-Folic Acid Supplementation with Regular Deworming Is Cost-Effective in Preventing Anaemia in Women of Reproductive Age in Vietnam  

PubMed Central

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

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

259

Discovery of a Novel Series of CRTH2 (DP2) Receptor Antagonists Devoid of Carboxylic Acids  

PubMed Central

Antagonism of the CRTH2 receptor represents a very attractive target for a variety of allergic diseases. Most CRTH2 antagonists known to date possess a carboxylic acid moiety, which is essential for binding. However, potential acid metabolites O-acyl glucuronides might be linked to idiosynchratic toxicity in humans. In this communication, we describe a new series of compounds that lack the carboxylic acid moiety. Compounds with high affinity (Ki < 10 nM) for the receptor have been identified. Subsequent optimization succeeded in reducing the high metabolic clearance of the first compounds in human and rat liver microsomes. At the same time, inhibition of the CYP isoforms was optimized, giving rise to stable compounds with an acceptable CYP inhibition profile (IC50 CYP2C9 and 2C19 > 1 ?M). Taken together, these data show that compounds devoid of carboxylic acid groups could represent an interesting alternative to current CRTH2 antagonists in development. PMID:24900284

2011-01-01

260

Folic acid-conjugated MnO nanoparticles as a T1 contrast agent for magnetic resonance imaging of tiny brain gliomas.  

PubMed

Detection of brain gliomas at the earliest stage is of great importance to improve outcomes, but it remains a most challenging task. In this study, oleic acid capped manganese oxide (MnO) nanoparticles (NPs) were prepared by the thermal decomposition of manganese oleate precursors and then transformed to water-dispersible MnO NPs by replacing oleic acid with N-(trimethoxysilylpropyl) ethylene diamine triacetic acid (TETT) silane. The covalently bonded TETT silane offers MnO NPs colloidal stability and abundant carboxylic functional groups allowing the further conjugation of the glioma-specific moiety, folic acid (FA). Moreover, the thin layer of TETT silane ensures a short distance between external Mn ion and water proton, which endows the FA-conjugated, TETT modified MnO (MnO-TETT-FA) NPs a longitudinal relaxivity as high as 4.83 mM(-1) s(-1). Accordingly, the in vivo magnetic resonance (MR) images demonstrated that MnO-TETT-FA NPs could efficiently enhance the MRI contrast for tiny brain gliomas. More importantly, due to the specificity of FA, MnO-TETT-FA NPs led to a clearer margin of the tiny glioma. This together with the good biocompatibility discloses the great potential of MnO-TETT-FA NPs as effective MRI contrast agents for the early diagnosis of brain gliomas. PMID:25335117

Chen, Ning; Shao, Chen; Qu, Yanming; Li, Shuai; Gu, Wei; Zheng, Tingting; Ye, Ling; Yu, Chunjiang

2014-11-26

261

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

PubMed

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

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

2013-01-01

262

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

PubMed

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

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

2010-11-01

263

Low Vitamin B6 but Not Homocyst(e)ine Is Associated With Increased Risk of Stroke and Transient Ischemic Attack in the Era of Folic Acid Grain Fortification  

Microsoft Academic Search

Background and Purpose—The introduction of cereal grain folic acid fortification in 1998 has reduced homocyst(e)ine (tHcy) concentrations in the US population. We performed a case-control study to determine the risk of stroke and transient ischemic attack (TIA) associated with tHcy and low vitamin status in a postfortification US sample. Methods—Consecutive cases with new ischemic stroke\\/TIA were compared with matched controls.

Peter J. Kelly; Vivian E. Shih; J. Philip Kistler; Megan Barron; Hang Lee; Roseann Mandell; Karen L. Furie

2010-01-01

264

An Excitatory Amino Acid Antagonist Blocks Cone Input to Sign-Conserving Second-Order Retinal Neurons  

Microsoft Academic Search

cis-2,3-Piperidinedicarboxylic acid (PDA), an excitatory amino acid antagonist, reversibly blocked cone input to OFF bipolars and horizontal cells, whereas ON bipolars were relatively unaffected. Kainic acid effects were also blocked, indicating a postsynaptic mechanism of action. The use of PDA helps to characterize one of two classes of excitatory amino acid synaptic receptors that mediate cone influence in the outer

Malcolm M. Slaughter; Robert F. Miller

1983-01-01

265

Design, synthesis, and preliminary activity evaluation of novel pyrimidine derivatives as Acid pump antagonists.  

PubMed

Acid-related diseases of the upper gastrointestinal tract, especially gastroesophageal reflux disease (GERD), remain a widespread problem worldwide. In this paper, we reported the design, synthesis, and preliminary gastric antisecretory activity evaluation of novel pyrimidine derivatives as acid pump antagonists. The gastric antisecretory activity assay results showed that all compounds displayed potent gastric antisecretory activity when gastric secretion was stimulated by histamine. The most potent compound 5g exhibited even similar gastric antisecretory activity compared with the control revaprazan, and the relative inhibition rate was 93.0%, which was worthy of further investigation. PMID:24995399

Song, Weiguo; Zhang, Xiaopan; Li, Shutao; Xu, Wenfang

2015-03-01

266

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

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

Agrawal, Sutapa; Fledderjohann, Jasmine; Vellakkal, Sukumar; Stuckler, David

2015-01-01

267

Estimation of serum and erythrocyte folate concentrations in the New Zealand adult population within a background of voluntary folic acid fortification.  

PubMed

National data on the blood folate status of New Zealand adults is lacking. The objective of this study was to describe the blood folate status and examine the predictors of blood folate status in a national sample of adults from New Zealand, a country with voluntary folic acid fortification. The 2008/09 New Zealand Adult Nutrition Survey was a nationwide multistage systematic random cross-sectional survey. Serum and erythrocyte folate concentrations were measured by microbiologic assay. The survey included 4721 participants aged ?15 y, 3359 of whom provided a nonfasting blood sample. Biochemical folate status was measured in 3277 participants. The median serum and erythrocyte folate concentrations were 23 and 809 nmol/L, respectively. The prevalence of biochemical folate deficiency, defined as plasma folate <6.8 nmol/L or erythrocyte folate <305 nmol/L, was 2%. Having breakfast daily compared with never eating breakfast was associated with 53% higher serum and 25% higher erythrocyte folate concentrations; consumers of fortified yeast extract spread had 17% higher serum and 14% higher erythrocyte folate concentrations than nonconsumers; daily users of folate-containing supplements compared with nonusers had 48% higher serum and 28% higher erythrocyte folate concentrations. The prevalence of biochemical folate deficiency in New Zealand adults is low. Participants who ate breakfast more frequently, consumed folate-fortified yeast, or used a daily folate supplement had higher blood folate concentrations. PMID:24174623

Bradbury, Kathryn E; Williams, Sheila M; Mann, Jim I; Brown, Rachel C; Parnell, Winsome; Skeaff, C Murray

2014-01-01

268

Inhibition Against Growth of Glioblastoma Multiforme In Vitro Using Etoposide-Loaded Solid Lipid Nanoparticles with p-Aminophenyl-?-d-Manno-Pyranoside and Folic Acid.  

PubMed

Solid lipid nanoparticles (SLNs) grafted with p-aminophenyl-?-d-manno-pyranoside (APMP) and folic acid (FA) (APMP-FA-SLNs) were applied to encapsulate 4'-demethylepipodophyllotoxin 9-(4,6-O-ethylidene-?-d-glucopyranoside) (etoposide) (ETP) for promoting the antiproliferation of malignant glioblastoma multiforme. ETP-loaded APMP-FA-SLNs (APMP-FA-ETP-SLNs) were used to penetrate the blood-brain barrier (BBB) and retard the propagation of U87MG cells. An incorporation of APMP and FA increased the particle size, the cytotoxicity to U87MG cells, and the permeability coefficient for propidium iodide and ETP across the BBB. In addition, an increase in the APMP and FA concentration reduced the zeta potential, the grafting efficiency of APMP and FA, the dissolution rate of ETP, and the transendothelial electrical resistance. Immunochemical staining images evidenced that APMP-FA-ETP-SLNs could infiltrate the BBB via glucose transporter 1 and recognize U87MG cells via folate receptor. APMP-FA-ETP-SLNs can be an effective pharmacotherapeutic formulation in targeting delivery to the brain and in inhibitory efficacy against tumorous cells for cancer therapy. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:1804-1814, 2015. PMID:25694089

Kuo, Yung-Chih; Lee, Chia-Hao

2015-05-01

269

Differential regulation of hepatic transcription factors in the Wistar rat offspring born to dams fed folic acid, vitamin B12 deficient diets and supplemented with omega-3 fatty acids.  

PubMed

Nutritional status of the mother is known to influence various metabolic adaptations required for optimal fetal development. These may be mediated by transcription factors like peroxisome proliferator activated receptors (PPARs), which are activated by long chain polyunsaturated fatty acids. The objective of the current study was to examine the expression of different hepatic transcription factors and the levels of global methylation in the liver of the offspring born to dams fed micronutrient deficient (folic acid and vitamin B12) diets and supplemented with omega-3 fatty acids. Female rats were divided into five groups (n = 8/group) as follows; control, folic acid deficient (FD), vitamin B12 deficient (BD) and omega-3 fatty acid supplemented groups (FDO and BDO). Diets were given starting from pre-conception and continued throughout pregnancy and lactation. Pups were dissected at the end of lactation. Liver tissues were removed; snap frozen and stored at -80°C. Maternal micronutrients deficiency resulted in lower (p<0.05) levels of pup liver docosahexaenoic acid (DHA) and arachidonic acid (ARA) as compared to the control group. Pup liver PPAR? and PPAR? expression was lower (p<0.05) in the BD group although there were no differences in the expression of SREBP-1c, LXR? and RXR? expression. Omega-3 fatty acids supplementation to this group normalized (p<0.05) levels of both PPAR? and PPAR? but reduced (p<0.05) SREBP-1c, LXR? and RXR? expression. There was no change in any of the transcription factors in the pup liver in the FD group. Omega-3 fatty acids supplementation to this group reduced (p<0.05) PPAR?, SREBP-1c and RXR? expression. Pup liver global methylation levels were higher (p<0.01) in both the micronutrients deficient groups and could be normalized (p<0.05) by omega-3 fatty acid supplementation. Our novel findings suggest a role for omega-3 fatty acids in the one carbon cycle in influencing the hepatic expression of transcription factors in the offspring. PMID:24587285

Meher, Akshaya; Joshi, Asmita; Joshi, Sadhana

2014-01-01

270

Analogues of ?-aminobutyric acid (GABA) and trans-4-aminocrotonic acid (TACA) substituted in the 2 position as GABAC receptor antagonists  

PubMed Central

?-Aminobutyric acid (GABA) and trans-4-aminocrotonic acid (TACA) have been shown to activate GABAC receptors. In this study, a range of C2, C3, C4 and N-substituted GABA and TACA analogues were examined for activity at GABAC receptors. The effects of these compounds were examined by use of electrophysiological recording from Xenopus oocytes expressing the human ?1 subunit of GABAC receptors with the two-electrode voltage-clamp method. trans-4-Amino-2-fluorobut-2-enoic acid was found to be a potent agonist (KD=2.43??M). In contrast, trans-4-amino-2-methylbut-2-enoic acid was found to be a moderately potent antagonist (IC50=31.0??M and KB=45.5??M). These observations highlight the possibility that subtle structural substitutions may change an agonist into an antagonist. 4-Amino-2-methylbutanoic acid (KD=189??M), 4-amino-2-methylenebutanoic acid (KD=182??M) and 4-amino-2-chlorobutanoic acid (KD=285??M) were weak partial agonists. The intrinsic activities of these compounds were 12.1%, 4.4% and 5.2% of the maximal response of GABA, respectively. These compounds more effectively blocked the effects of the agonist, GABA, giving rise to KB values of 53??M and 101??M, respectively. The sulphinic acid analogue of GABA, homohypotaurine, was found to be a potent partial agonist (KD=4.59??M, intrinsic activity 69%). It was concluded that substitution of a methyl or a halo group in the C2 position of GABA or TACA is tolerated at GABAC receptors. However, there was dramatic loss of activity when these groups were substituted at the C3, C4 and nitrogen positions of GABA and TACA. Molecular modelling studies on a range of active and inactive compounds indicated that the agonist/competitive antagonist binding site of the GABAC receptor may be smaller than that of the GABAA and GABAB receptors. It is suggested that only compounds that can attain relatively flat conformations may bind to the GABAC receptor agonist/competitive antagonist binding site. PMID:9422798

Chebib, Mary; Vandenberg, Robert J; Johnston, Graham A R

1997-01-01

271

Mechanistic Insights into Folic Acid-dependent Vascular Protection: Dihydrofolate reductase-mediated Reduction in Oxidant Stress in Endothelial Cells and Angiotensin II-Infused Mice  

PubMed Central

Background Folate supplementation improves endothelial function in patients with hyperhomocysteinemia. Mechanistic insights into potential benefits of folate on vascular function in general population however, remain mysterious. Methods and Results Expression of dihydrofolate reductase (DHFR) was markedly increased by folic acid (FA, 50 µmol/L, 24 hr) treatment in endothelial cells. Tetrahydrofolate (THF) is formed after incubation of purified DHFR or cellular extracts with 50 µmol/L of substrate dihydrofolic acid. THF could then be detected and quantified by high performance liquid chromatography (HPLC) with a fluorescent detector (295/365 nm). Using this novel and sensitive assay, we found that DHFR activity was significantly increased by FA. Furthermore, FA improved redox status of Ang II treated cells by increasing H4B and NO• bioavailability while decreasing superoxide (O2•?) production. It however failed to restore NO• levels in DHFR siRNA-transfected or methotrexate pre-treated cells, implicating a specific and intermediate role of DHFR. In mice orally administrated with FA (15 mg/kg/day, 16 days), endothelium upregulation of DHFR expression and activity occurred in correspondence to improved NO• and H4B bioavailability, and this was highly effective in reducing Ang II infusion (0.7 mg/kg/day, 14 days)-stimulated aortic O2•? production. 5’-methyltetrahydrofolate (5’-MTHF levels, GTPCH1 expression and activity remained unchanged in response to FA or Ang II treatment in vitro and in vivo. Conclusions FA supplementation improves endothelial NO• bioavailability via upregulation of DHFR expression and activity, and protects endothelial cells from Ang II-provoked oxidant stress both in vitro and in vivo. These observations likely represent a novel mechanism (intermediate role of DHFR) whereby FA induces vascular protection. PMID:19660467

Gao, Ling; Chalupsky, Karel; Stefani, Enrico; Cai, Hua

2009-01-01

272

Transcriptomic insights into antagonistic effects of gibberellin and abscisic acid on petal growth in Gerbera hybrida  

PubMed Central

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

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

273

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

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-?4 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

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

274

Folic Acid Protects against Lipopolysaccharide-Induced Preterm Delivery and Intrauterine Growth Restriction through Its Anti-Inflammatory Effect in Mice  

PubMed Central

Increasing evidence demonstrates that maternal folic acid (FA) supplementation during pregnancy reduces the risk of neural tube defects, but whether FA prevents preterm delivery and intrauterine growth restriction (IUGR) remains obscure. Previous studies showed that maternal lipopolysaccharide (LPS) exposure induces preterm delivery, fetal death and IUGR in rodent animals. The aim of this study was to investigate the effects of FA on LPS-induced preterm delivery, fetal death and IUGR in mice. Some pregnant mice were orally administered with FA (0.6, 3 or 15 mg/kg) 1 h before LPS injection. As expected, a high dose of LPS (300 ?g/kg, i.p.) on gestational day 15 (GD15) caused 100% of dams to deliver before GD18 and 89.3% of fetuses dead. A low dose of LPS (75 ?g/kg, i.p.) daily from GD15 to GD17 resulted in IUGR. Interestingly, pretreatment with FA prevented LPS-induced preterm delivery and fetal death. In addition, FA significantly attenuated LPS-induced IUGR. Further experiments showed that FA inhibited LPS-induced activation of nuclear factor kappa B (NF-?B) in mouse placentas. Moreover, FA suppressed LPS-induced NF-?B activation in human trophoblast cell line JEG-3. Correspondingly, FA significantly attenuated LPS-induced upregulation of cyclooxygenase (COX)-2 in mouse placentas. In addition, FA significantly reduced the levels of interleukin (IL)-6 and keratinocyte-derived cytokine (KC) in amniotic fluid of LPS-treated mice. Collectively, maternal FA supplementation during pregnancy protects against LPS-induced preterm delivery, fetal death and IUGR through its anti-inflammatory effects. PMID:24324824

Dong, Xu-Ting; Zhou, Jun; Chen, Xue; Wang, Hua; Wu, Shu-Xian; Xia, Mi-Zhen; Zhang, Cheng; Xu, De-Xiang

2013-01-01

275

Multifunctional core/shell nanoparticles cross-linked polyetherimide-folic acid as efficient Notch-1 siRNA carrier for targeted killing of breast cancer.  

PubMed

In gene therapy, how genetic therapeutics can be efficiently and safely delivered into target tissues/cells remains a major obstacle to overcome. To address this issue, nanoparticles consisting of non-covalently coupled polyethyleneimine (PEI) and folic acid (FA) to the magnetic and fluorescent core/shell of Fe3O4@SiO2(FITC) was tested for their ability to deliver Notch-1 shRNA. Our results showed that Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanoparticles are 64?nm in diameter with well dispersed and superparamagnetic. These nanoparticles with on significant cytotoxicity are capable of delivering Notch-1 shRNA into human breast cancer MDA-MB-231 cells with high efficiency while effectively protected shRNA from degradation by exogenous DNaseI and nucleases. Magnetic resonance (MR) imaging and fluorescence microscopy showed significant preferential uptake of Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex by MDA-MB-231 cells. Transfected MDA-MB-231 cells exhibited significantly decreased expression of Notch-1, inhibited cell proliferation, and increased cell apoptosis, leading to the killing of MDA-MB-231 cells. In light of the magnetic targeting capabilities of Fe3O4@SiO2(FITC)/PEI-FA, our results show that by complexing with a second molecular targeting therapeutic, such as Notch-1 shRNA in this report, Fe3O4@SiO2(FITC)/PEI-FA can be exploited as a novel, non-viral, and concurrent targeting delivery system for targeted gene therapy as well as for MR imaging in cancer diagnosis. PMID:25400232

Yang, Hong; Li, Ying; Li, Tingting; Xu, Min; Chen, Yin; Wu, Chunhui; Dang, Xitong; Liu, Yiyao

2014-01-01

276

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

NASA Astrophysics Data System (ADS)

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

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

2013-12-01

277

Multifunctional Core/Shell Nanoparticles Cross-linked Polyetherimide-folic Acid as Efficient Notch-1 siRNA Carrier for Targeted Killing of Breast Cancer  

PubMed Central

In gene therapy, how genetic therapeutics can be efficiently and safely delivered into target tissues/cells remains a major obstacle to overcome. To address this issue, nanoparticles consisting of non-covalently coupled polyethyleneimine (PEI) and folic acid (FA) to the magnetic and fluorescent core/shell of Fe3O4@SiO2(FITC) was tested for their ability to deliver Notch-1 shRNA. Our results showed that Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanoparticles are 64?nm in diameter with well dispersed and superparamagnetic. These nanoparticles with on significant cytotoxicity are capable of delivering Notch-1 shRNA into human breast cancer MDA-MB-231 cells with high efficiency while effectively protected shRNA from degradation by exogenous DNaseI and nucleases. Magnetic resonance (MR) imaging and fluorescence microscopy showed significant preferential uptake of Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex by MDA-MB-231 cells. Transfected MDA-MB-231 cells exhibited significantly decreased expression of Notch-1, inhibited cell proliferation, and increased cell apoptosis, leading to the killing of MDA-MB-231 cells. In light of the magnetic targeting capabilities of Fe3O4@SiO2(FITC)/PEI-FA, our results show that by complexing with a second molecular targeting therapeutic, such as Notch-1 shRNA in this report, Fe3O4@SiO2(FITC)/PEI-FA can be exploited as a novel, non-viral, and concurrent targeting delivery system for targeted gene therapy as well as for MR imaging in cancer diagnosis. PMID:25400232

Yang, Hong; Li, Ying; Li, Tingting; Xu, Min; Chen, Yin; Wu, Chunhui; Dang, Xitong; Liu, Yiyao

2014-01-01

278

Earlier Initiation and Use of a Greater Number of Iron-Folic Acid Supplements during Pregnancy Prevents Early Neonatal Deaths in Nepal and Pakistan  

PubMed Central

Introduction Early neonatal deaths account for 75% of neonatal deaths globally. Antenatal iron-folic acid (IFA) supplementation has significantly reduced the risk of early neonatal deaths in China and Indonesia. We investigated the impact of antenatal IFA supplements on the risk of early neonatal deaths in Nepal and Pakistan during the last decade. Methods Data from the most recent singleton live-births of 8,186 from two Nepal Demographic and Health Surveys (DHS) and 13,034 from two Pakistan DHS were selected for the current study. The primary outcome was early neonatal deaths and the main study variable was antenatal IFA supplementation. Analyses used multivariate Cox proportional regression, adjusted for the cluster sampling design and for 18 potential confounders. Findings The adjusted risk of early neonatal deaths was significantly reduced by 51% (aHR?=?0.49, 95% CI?=?0.32–0.75) in Nepal and 23% (aHR?=?0.77, 95% CI?=?0.59–0.99) in Pakistan with any use of IFA compared to none. When IFA supplementation started at or before the 5th month of pregnancy, the adjusted risk of early neonatal mortality was significantly reduced by 53% in Nepal, and 28% in Pakistan, compared to no IFA. When >90 IFA supplements were used and started at or before 5th months, the adjusted risk of early neonatal deaths was significantly reduced by 57% in Nepal, and 45% in Pakistan. In Nepal 4,600 and in Pakistan 75,000 early neonatal deaths could be prevented annually if all pregnant women used >90 IFA supplements and started at or before the 5th month of pregnancy. Conclusions Any use of IFA supplements was significantly associated with reduced risk of early neonatal deaths in Nepal and Pakistan. The greatest mortality sparing effect of IFA on early neonatal deaths in both countries was with early initiation and use of a greater number of supplements. PMID:25398011

Nisar, Yasir Bin; Dibley, Michael J.

2014-01-01

279

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

PubMed

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

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

2013-12-20

280

Folic acid protects against lipopolysaccharide-induced preterm delivery and intrauterine growth restriction through its anti-inflammatory effect in mice.  

PubMed

Increasing evidence demonstrates that maternal folic acid (FA) supplementation during pregnancy reduces the risk of neural tube defects, but whether FA prevents preterm delivery and intrauterine growth restriction (IUGR) remains obscure. Previous studies showed that maternal lipopolysaccharide (LPS) exposure induces preterm delivery, fetal death and IUGR in rodent animals. The aim of this study was to investigate the effects of FA on LPS-induced preterm delivery, fetal death and IUGR in mice. Some pregnant mice were orally administered with FA (0.6, 3 or 15 mg/kg) 1 h before LPS injection. As expected, a high dose of LPS (300 ?g/kg, i.p.) on gestational day 15 (GD15) caused 100% of dams to deliver before GD18 and 89.3% of fetuses dead. A low dose of LPS (75 ?g/kg, i.p.) daily from GD15 to GD17 resulted in IUGR. Interestingly, pretreatment with FA prevented LPS-induced preterm delivery and fetal death. In addition, FA significantly attenuated LPS-induced IUGR. Further experiments showed that FA inhibited LPS-induced activation of nuclear factor kappa B (NF-?B) in mouse placentas. Moreover, FA suppressed LPS-induced NF-?B activation in human trophoblast cell line JEG-3. Correspondingly, FA significantly attenuated LPS-induced upregulation of cyclooxygenase (COX)-2 in mouse placentas. In addition, FA significantly reduced the levels of interleukin (IL)-6 and keratinocyte-derived cytokine (KC) in amniotic fluid of LPS-treated mice. Collectively, maternal FA supplementation during pregnancy protects against LPS-induced preterm delivery, fetal death and IUGR through its anti-inflammatory effects. PMID:24324824

Zhao, Mei; Chen, Yuan-Hua; Dong, Xu-Ting; Zhou, Jun; Chen, Xue; Wang, Hua; Wu, Shu-Xian; Xia, Mi-Zhen; Zhang, Cheng; Xu, De-Xiang

2013-01-01

281

Folic Acid Supplementation during Pregnancy Induces Sex-Specific Changes in Methylation and Expression of Placental 11?-Hydroxysteroid Dehydrogenase 2 in Rats.  

PubMed

In the placenta, 11?-hydroxysteroid dehydrogenase type 2 (11?-HSD2) limits fetal glucocorticoid exposure and its inhibition has been associated to low birth weight. Its expression, encoded by the HSD11B2 gene is regulated by DNA methylation. We hypothesized that maternal diets supplemented with folic acid (FA) during pregnancy modify the expression of placental HSD11B2 through gene methylation. Wistar rats were fed with high (8 mg/kg) or normal low (1mg/kg, control) levels of FA during pregnancy. Concentrations of mRNA and protein in placentas were determined by qRT-PCR and Western blot respectively. Methylation in five CpG sites of the placental HSD11B2 promoter (-378 to -275) was analyzed by bacterial cloning and subsequent sequencing. In the FA-supplemented group, mRNA and protein levels of 11?-HSD2 decreased by 58% and increased by 89%, respectively, only in placentas attached to males. In controls, most CpG sites were not methylated except for the CpG2 site which was 80% methylated. CpG2 methylation level increased under the FA treatment; however, only in placentas attached to females was this increase significant (113%). This change was not related to HSD11B2 expression. Fetal weight of females from FA- supplemented mothers was 6% higher than females from control mothers. In conclusion, this is the first study reporting that FA over supplementation during pregnancy modifies the placental HSD11B2 gene expression and methylation in a sex-dependent manner, suggesting that maternal diets with high content of FA can induce early sex-specific responses, which may lead to long-term consequences for the offspring. PMID:25793274

Penailillo, Reyna; Guajardo, Angelica; Llanos, Miguel; Hirsch, Sandra; Ronco, Ana Maria

2015-01-01

282

Folic Acid Supplementation during Pregnancy Induces Sex-Specific Changes in Methylation and Expression of Placental 11?-Hydroxysteroid Dehydrogenase 2 in Rats  

PubMed Central

In the placenta, 11?-hydroxysteroid dehydrogenase type 2 (11?-HSD2) limits fetal glucocorticoid exposure and its inhibition has been associated to low birth weight. Its expression, encoded by the HSD11B2 gene is regulated by DNA methylation. We hypothesized that maternal diets supplemented with folic acid (FA) during pregnancy modify the expression of placental HSD11B2 through gene methylation. Wistar rats were fed with high (8 mg/kg) or normal low (1mg/kg, control) levels of FA during pregnancy. Concentrations of mRNA and protein in placentas were determined by qRT-PCR and Western blot respectively. Methylation in five CpG sites of the placental HSD11B2 promoter (?378 to ?275) was analyzed by bacterial cloning and subsequent sequencing. In the FA-supplemented group, mRNA and protein levels of 11?-HSD2 decreased by 58% and increased by 89%, respectively, only in placentas attached to males. In controls, most CpG sites were not methylated except for the CpG2 site which was 80% methylated. CpG2 methylation level increased under the FA treatment; however, only in placentas attached to females was this increase significant (113%). This change was not related to HSD11B2 expression. Fetal weight of females from FA- supplemented mothers was 6% higher than females from control mothers. In conclusion, this is the first study reporting that FA over supplementation during pregnancy modifies the placental HSD11B2 gene expression and methylation in a sex-dependent manner, suggesting that maternal diets with high content of FA can induce early sex-specific responses, which may lead to long-term consequences for the offspring. PMID:25793274

Penailillo, Reyna; Guajardo, Angelica; Llanos, Miguel; Hirsch, Sandra; Ronco, Ana Maria

2015-01-01

283

Adequate but not supplemental folic acid combined with soy isoflavones during early life improves bone health at adulthood in male mice.  

PubMed

Previous investigations from our laboratory have demonstrated that neonatal exposure to soy isoflavones (ISO) improves bone outcomes in CD-1 mice at adulthood with greater benefits in females than males. This study determined whether early-life exposure to supplemental folic acid (FA) - that may enhance DNA methylation of target genes - in combination with ISO provides greater benefits to male bone development than ISO alone. CD-1 dams were randomized to a low (0 mg/kg diet), adequate (2 mg/kg diet) or supplemental (8 mg/kg diet) level of FA during pregnancy and lactation. Offspring received corn oil or ISO (7 mg/kg of body weight per day) from postnatal day 1-10. From weaning, males were fed adequate FA and studied to age 4 months. Offspring exposed to adequate FA+ISO had multiple benefits to bone health: higher (P<.05) bone mineral density (BMD) and greater (P<.05) resistance to fracture at the femur and lumbar spine than mice exposed to adequate FA alone. Exposure to supplemental FA+ISO resulted in higher (P<.05) serum osteoprotegerin (OPG), and a higher ratio of OPG to receptor activator for nuclear factor ?? ligand (RANKL) but did not result in greater BMD or strength at the femur or lumbar spine than supplemental FA alone. In conclusion, early-life exposure to adequate FA+ISO provided functional benefits to male bone development, while improvements induced by supplemental FA+ISO were limited to a higher level of serum OPG. Mechanistic studies are needed to better understand how FA and ISO improve bone development in male offspring. PMID:23643520

Kaludjerovic, Jovana; Ward, Wendy E

2013-10-01

284

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

PubMed

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

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

2014-03-01

285

Individual and Facility-Level Determinants of Iron and Folic Acid Receipt and Adequate Consumption among Pregnant Women in Rural Bihar, India  

PubMed Central

Background In Bihar, India, high maternal anemia prevalence and low iron and folic acid supplement (IFA) receipt and consumption have continued over time despite universal IFA distribution and counseling during pregnancy. Purpose To examine individual and facility-level determinants of IFA receipt and consumption among pregnant women in rural Bihar, India. Methods Using District Level Household Survey (2007–08) data, multilevel modeling was conducted to examine the determinants of two outcomes: IFA receipt (any IFA receipt vs. none) and IFA consumption (?90 days vs. <90 days). Individual-level and facility-level factors were included. Factor analysis was utilized to construct antenatal care (ANC) quality and health sub-center (HSC) capacity variables. Results Overall, 37% of women received any IFA during their last pregnancy. Of those, 24% consumed IFA for 90 or more days. Women were more likely to receive any IFA when they received additional ANC services and counseling, and attended ANC earlier and more frequently. Significant interactions were found between ANC quality factors (odds ratio (OR): 0.37, 95% confidence interval (CI): 0.25, 0.56) and between ANC services and ANC timing and frequency (OR: 0.68, 95% CI: 0.56, 0.82). No HSC factors were significantly associated with IFA receipt. Women were more likely to consume IFA for ?90 days if they attended at least 4 ANC check-ups and received more ANC services. IFA supply at the HSC (OR: 1.37, 95% CI: 1.04, 1.82) was also significantly associated with IFA consumption. Conclusions Our findings indicate that individual and ANC factors (timing, frequency, and quality) play a key role in facilitating IFA receipt and consumption. Although HSC capacity factors were not found to influence our outcomes, significant variation at the facility level indicates unmeasured factors that could be important to address in future interventions. PMID:25793866

Wendt, Amanda; Stephenson, Rob; Young, Melissa; Webb-Girard, Amy; Hogue, Carol; Ramakrishnan, Usha; Martorell, Reynaldo

2015-01-01

286

Piperazine-2,3-dicarboxylic acid Derivatives as Dual Antagonists of NMDA and GluK1-Containing Kainate Receptors  

PubMed Central

Competitive N-methyl-D-aspartate receptor (NMDAR) antagonists bind to the GluN2 subunit, of which there are four types (GluN2A-D). We report that some N1-substituted derivatives of cis-piperazine-2,3-dicarboxylic acid display improved relative affinity for GluN2C and GluN2D versus GluN2A and GluN2B. These derivatives also display subtype-selectivity among the more distantly related kainate receptor family. Compounds 18i and (?)-4 were the most potent kainate receptor antagonists and 18i was selective for GluK1 versus GluK2, GluK3 and AMPA receptors. Modeling studies revealed structural features required for activity at GluK1 subunits and suggested that S674 was vital for antagonist activity. Consistent with this hypothesis, replacing the equivalent residue in GluK3 (alanine) with a serine imparts 18i antagonist activity. Antagonists with dual GluN2D and GluK1 antagonist activity may have beneficial effects in various neurological disorders. Consistent with this idea, antagonist 18i (30 mg/Kg i.p.) showed antinociceptive effects in an animal model of mild nerve injury. PMID:22111545

Irvine, Mark W.; Costa, Blaise M.; Dlaboga, Daniel; Culley, Georgia; Hulse, Richard; Scholefield, Caroline L.; Atlason, Palmi; Fang, Guangyu; Eaves, Richard; Morley, Richard; Mayo-Martin, Maria B.; Amici, Mascia; Bortolotto, Zuner A.; Donaldson, Lucy; Collingridge, Graham L.; Molnár, Elek; Monaghan, Daniel T.; Jane, David E.

2011-01-01

287

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

PubMed Central

Subcutaneous injection of sodium deoxycholic acid into the anterior of the back of male ddY mice elicited dose-dependent scratching of the injected site with the forepaws and hindpaws.Up to 100??g of sodium deoxycholic acid induced no significant increase in vascular permeability at the injection site as assessed by a dye leakage method.Bradykinin (BK) B2 receptor antagonists, FR173657 and Hoe140, significantly decreased the frequency of scratching induced by sodium deoxycholic acid.Treatment with aprotinin to inhibit tissue kallikrein reduced the scratching behaviour induced by sodium deoxycholic acid, whereas treatment with soybean trypsin inhibitor to inhibit plasma kallikrein did not.Although injection of kininase II inhibitor, lisinopril together with sodium deoxycholic acid did not alter the scratching behaviour, phosphoramidon, a neutral endopeptidase inhibitor, significantly increased the frequency of scratching.Homogenates of the skin excised from the backs of mice were subjected to gel-filtration column chromatography followed by an assay of kinin release by trypsin from each fraction separated. Less kinin release from the fractions containing kininogen of low molecular weight was observed in the skin injected with sodium deoxycholic acid than in normal skin.The frequency of scratching after the injection of sodium deoxycholic acid in plasma kininogen-deficient Brown Norway Katholiek rats was significantly lower than that in normal rats of the same strain, Brown Norway Kitasato rats.These results indicate that BK released from low-molecular-weight kininogen by tissue kallikrein, but not from high-molecular-weight kininogen by plasma kallikrein, may be involved in the scratching behaviour induced by the injection of sodium deoxycholic acid in the rodent. PMID:10051136

Hayashi, Izumi; Majima, Masataka

1999-01-01

288

Folic acid-conjugated LaF3:Yb,Tm@SiO2 nanoprobes for targeting dual-modality imaging of upconversion luminescence and X-ray computed tomography.  

PubMed

Development of multimodal contrast agents for in vivo simultaneous multimodality imaging is an emerging interdiscipline that is paving the avenue toward the goal of personalized medicine. Herein, folic acid-conjugated silica-modified LaF(3):Yb,Tm upconversion nanoparticles (UCNPs@SiO(2)-FA) with high La content in a single particle were strategically designed and prepared for simultaneously targeting dual-modality imaging of upconversion luminescence (UCL) and X-ray computed tomography (CT). LaF(3) UCNPs were synthesized by a novel oleic acid (OA)/ionic liquid (IL) two-phase system. Afterward, a folic acid molecule was covalently anchored on the surface of UCNPs with a silane coupling agent. The UCNPs@SiO(2)-FA exhibits good stability, water dispersibility and solubility, low cytotoxicity, good biocompatibility, highly selective targeting, excellent X-ray attenuation, and UCL emission under excitation at 980 nm. In vivo UCL and CT images of mice show the UCNPs@SiO(2)-FA can be used in targeting dual-modality imaging. These results suggest that the as-prepared nanoprobe is a good candidate with excellent imaging and targeting ability for targeting dual-modality imaging of UCL and CT. PMID:23134318

Ma, Jiebing; Huang, Peng; He, Meng; Pan, Liyuan; Zhou, Zhijun; Feng, Lili; Gao, Guo; Cui, Daxiang

2012-12-01

289

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

SciTech Connect

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

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

2009-08-28

290

Synthesis and biological evaluation of quinoline salicylic acids as P-selectin antagonists.  

PubMed

Leukocyte recruitment of sites of inflammation and tissue injury involves leukocyte rolling along the endothelial wall, followed by firm adherence of the leukocyte, and finally transmigration of the leukocyte across cell junctions into the underlying tissue. The initial rolling step is mediated by the interaction of leukocyte glycoproteins containing active moieties such as sialyl Lewisx (sLex) with P-selectin expressed on endothelial cells. Consequently, inhibition of this interaction by means of a small molecule P-selectin antagonist is an attractive strategy for the treatment of inflammatory diseases such as arthritis. High-throughput screening of the Wyeth chemical library identified the quinoline salicylic acid class of compounds (1) as antagonists of P-selectin, with potency in in vitro and cell-based assays far superior to that of sLex. Through iterative medicinal chemistry, we identified analogues with improved P-selectin activity, decreased inhibition of dihydrooratate dehydrogenase, and acceptable CYP profiles. Lead compound 36 was efficacious in the rat AIA model of rheumatoid arthritis. PMID:17201408

Kaila, Neelu; Janz, Kristin; DeBernardo, Silvano; Bedard, Patricia W; Camphausen, Raymond T; Tam, Steve; Tsao, Desirée H H; Keith, James C; Nickerson-Nutter, Cheryl; Shilling, Adam; Young-Sciame, Ruth; Wang, Qin

2007-01-11

291

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

PubMed

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

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

1992-01-01

292

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

PubMed Central

Background In 2010 a Cochrane review confirmed that folic acid (FA) supplementation prevents the first- and second-time occurrence of neural tube defects (NTDs). At present some evidence from observational studies supports the hypothesis that FA supplementation can reduce the risk of all congenital malformations (CMs) or the risk of a specific and selected group of them, namely cardiac defects and oral clefts. Furthermore, the effects on the prevention of prematurity, foetal growth retardation and pre-eclampsia are unclear. Although the most common recommendation is to take 0.4 mg/day, the problem of the most appropriate dose of FA is still open. The aim of this project is to assess the effect a higher dose of peri-conceptional FA supplementation on reducing the occurrence of all CMs. Other aims include the promotion of pre-conceptional counselling, comparing rates of selected CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age, abruptio placentae. Methods/Design This project is a joint effort by research groups in Italy and the Netherlands. Women of childbearing age, who intend to become pregnant within 12 months are eligible for the studies. Women are randomly assigned to receive 4 mg of FA (treatment in study) or 0.4 mg of FA (referent treatment) daily. Information on pregnancy outcomes are derived from women-and-physician information. We foresee to analyze the data considering all the adverse outcomes of pregnancy taken together in a global end point (e.g.: CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age). A total of about 1,000 pregnancies need to be evaluated to detect an absolute reduction of the frequency of 8%. Since the sample size needed for studying outcomes separately is large, this project also promotes an international prospective meta-analysis. Discussion The rationale of these randomized clinical trials (RCTs) is the hypothesis that a higher intake of FA is related to a higher risk reduction of NTDs, other CMs and other adverse pregnancy outcomes. Our hope is that these trials will act as catalysers, and lead to other large RCTs studying the effects of this supplementation on CMs and other infant and maternal outcomes. Trial registration Italian trial: ClinicalTrials.gov Identifier: NCT01244347. Dutch trial: Dutch Trial Register ID: NTR3161. PMID:24884885

2014-01-01

293

Subtype-Selective Antagonists of Lysophosphatidic Acid Receptors Inhibit Platelet Activation Triggered by the Lipid Core of Atherosclerotic Plaques  

Microsoft Academic Search

Background—Lysophosphatidic acid (LPA) is a platelet-activating component of mildly oxidized LDL (mox-LDL) and lipids isolated from human atherosclerotic plaques. Specific antagonists of platelet LPA receptors could be useful inhibitors of thrombus formation in patients with cardiovascular disease. Methods and Results—Short-chain analogs of phosphatidic acid (PA) were examined for their effect on two initial platelet responses, platelet shape change and Ca2

Enno Rother; Richard Brandl; Daniel L. Baker; Pankaj Goyal; Harry Gebhard; Gabor Tigyi; Wolfgang Siess

2010-01-01

294

Spinal bicuculline produces hypersensitivity of dorsal horn neurons: effects of excitatory amino acid antagonists.  

PubMed

In this study, we sought to characterize the effects of focal GABA(A) receptor antagonism on spontaneous and evoked activity in dorsal horn neurons of the alpha-chloralose anesthetized cat. Bicuculline (0.5, 1.0 mM) applied near the neurons through a transparenchymal dialysis fiber resulted in increased evoked activity in nociceptive dorsal horn neurons. Hair deflection was the stimulus most affected, followed by both low and high threshold tonic mechanical stimulation of the receptive field. In addition, neurons displayed increased background discharge and a subpopulation developed an increased afterdischarge to noxious mechanical stimulation. This is in contrast to our previous work with glycine receptor antagonism where only the evoked response to hair follicle activation was significantly enhanced. Subsequent co-administration of an NMDA receptor antagonist (AP-7, 2.0 mM) was without any apparent effect on either basal or bicuculline-enhanced responses. Co-administration of a non-NMDA excitatory amino acid receptor antagonist (CNQX, 1.0 mM) with the bicuculline non-selectively blocked both low and high threshold mechanical input. The inability of AP-7 to reverse the bicuculline-associated hyperreactivity also contrasts with the AP-7 reversal of the strychnine-associated hyperreactivity. These results point out that, while GABA and glycine are frequently co-localized in cells of the spinal dorsal horn and both appear to mediate tonic inhibitory control systems, they are not at all equivalent and are subject to different modulatory pharmacologies. Removal of each influence may model a different component of neuropathic pain. PMID:9766836

Sorkin, L S; Puig, S; Jones, D L

1998-08-01

295

LE135, a retinoid acid receptor antagonist, produces pain through direct activation of TRP channels  

PubMed Central

Background and PurposeRetinoids, through their activation of retinoic acid receptors (RARs) and retinoid X receptors, regulate diverse cellular processes, and pharmacological intervention in their actions has been successful in the treatment of skin disorders and cancers. Despite the many beneficial effects, administration of retinoids causes irritating side effects with unknown mechanisms. Here, we demonstrate that LE135 [4-(7,8,9,10-tetrahydro-5,7,7,10,10-pentamethyl-5H-benzo[e]naphtho[2,3-b][1,4]diazepin-13-yl)benzoic acid], a selective antagonist of RAR?, is a potent activator of the capsaicin (TRPV1) and wasabi (TRPA1) receptors, two critical pain-initiating cation channels. Experimental ApproachWe performed to investigate the excitatory effects of LE135 on TRPV1 and TRPA1 channels expressed in HEK293T cells and in dorsal root ganglia neurons with calcium imaging and patch-clamp recordings. We also used site-directed mutagenesis of the channels to determine the structural basis of LE135-induced activation of TRPV1 and TRPA1 channels and behavioural testing to examine if pharmacological inhibition and genetic deletion of the channels affected LE135-evoked pain-related behaviours. Key ResultsLE135 activated both the capsaicin receptor (TRPV1) and the allyl isothiocyanate receptor (TRPA1) heterologously expressed in HEK293T cells and endogenously expressed by sensory nociceptors. Mutations disrupting the capsaicin-binding site attenuated LE135 activation of TRPV1 channels and a single mutation (K170R) eliminated TRPA1 activity evoked by LE135. Intraplantar injection of LE135 evoked pain-related behaviours. Both TRPV1 and TRPA1 channels were involved in LE135-elicited pain-related responses, as shown by pharmacological and genetic ablation studies. Conclusions and ImplicationsThis blocker of retinoid acid signalling also exerted non-genomic effects through activating the pain-initiating TRPV1 and TRPA1 channels. PMID:24308840

Yin, Shijin; Luo, Jialie; Qian, Aihua; Yu, Weihua; Hu, Hongzhen

2014-01-01

296

The prevalence of low serum vitamin B-12 status in the absence of anemia or macrocytosis did not increase among older U.S. adults after mandatory folic acid fortification.  

PubMed

Whether folic acid fortification and supplementation at the population level have led to a higher prevalence of vitamin B-12 deficiency in the absence of anemia remains to be examined among a nationally representative sample of older U.S. adults. We assessed the prevalence of low vitamin B-12 status in the absence of anemia or macrocytosis before and after fortification among adults aged >50 y using cross-sectional data from the NHANES 1991-1994 (prefortification) and 2001-2006 (postfortification). We compared the prefortification and postfortification prevalence of multiple outcomes, including serum vitamin B-12 deficiency (<148 pmol/L) and marginal deficiency (148-258 pmol/L) with and without anemia (hemoglobin <130 g/L for men, <120 g/L for women) and with and without macrocytosis (mean cell volume >100 fL) using multinomial logistic regression, adjusting for age, sex, ethnicity, body mass index, C-reactive protein, and vitamin B-12 supplement use. Prefortification and postfortification serum vitamin B-12 deficiency without anemia [4.0 vs. 3.9%; adjusted prevalence ratio (aPR) (95% CI): 0.98 (0.67, 1.44)] or without macrocytosis [4.2 vs. 4.1%; aPR (95% CI): 0.96 (0.65, 1.43)] remained unchanged. Marginal deficiency without anemia [25.1 vs. 20.7%; aPR (95% CI): 0.82 (0.72, 0.95)] or without macrocytosis [25.9 vs. 21.3%; aPR (95% CI): 0.82 (0.72, 0.94)] were both significantly lower after fortification. After fortification, higher folic acid intake was associated with a lower prevalence of low serum B-12 status in the absence of anemia or macrocytosis. Results suggest that the prevalence of low serum B-12 status in the absence of anemia or macrocytosis among older U.S. adults did not increase after fortification. Thus, at the population level, we found no evidence to support concerns that folic acid adversely affected the clinical presentation of vitamin B-12 deficiency among older adults. PMID:24306216

Qi, Yan Ping; Do, Ann N; Hamner, Heather C; Pfeiffer, Christine M; Berry, Robert J

2014-02-01

297

An unblinded, randomised phase II study of platinum-based chemotherapy with vitamin B12 and folic acid supplementation in the treatment of lung cancer with plasma homocysteine blood levels as a biomarker of severe neutropenic toxicity  

PubMed Central

Background Vitamin B12 and folic acid (referred to as vitamin supplementation) improves the toxicity profile of pemetrexed containing regimens. Low baseline vitamin B12 and folate levels are reflected in a raised total homocysteine level (HC). Studies have suggested that pretreatment HC levels predict neutropenia toxicity. We have tested supplementation with vitamin B12 and folate in non-pemetrexed platinum-based regimens to decrease treatment-related toxicity and looked for a correlation between toxicity and change in homocysteine levels. Patient and method Eighty-three patients with advanced lung cancer and malignant mesothelioma were randomly assigned to receive platinum-based chemotherapy with (arm A) or without (arm B) vitamin B12 and folic acid supplementation. The primary end point was grade 3/4 neutropenia and death within 30?days of treatment. Secondary end points included quality of life, overall survival (OS) and the relationship between baseline and post supplementation HC levels and toxicity. Results In the intention-to-treat population, no significant difference was seen between the two groups with respect to chemotherapy-induced grade 3/4 neutropenia and death within 30?days of chemotherapy (36% vs 37%; p=0.966, emesis (2% vs 6%; p=0.9) or OS (12.3?months vs 7?months; p=0.41). There was no significant difference in survival rates by baseline HC level (p=0.9). Decrease in HC with vitamin supplementation was less frequent than expected. High baseline HC levels decreased with vitamin supplementation in only 9/36 (25%) patients (successful supplementation). Post hoc analysis showed that patients in arm A who were successfully supplemented (9/36=25%) had less neutropenic toxicity (0% vs 69%; p=0.02) compared to unsupplemented patients. Conclusions The addition of vitamin B12 and folic acid to platinum-containing regimens did not overall improve the toxicity, quality of life or OS. Rates of grade 3/4 neutropenia at 36/37% was as predicted. Further studies to increase the rate of successful supplementation and to further test the biomarker potential of post supplementation HC levels in predicting chemotherapy-induced neutropenia in platinum-based chemotherapy are warranted. Trial registration number: EudracCT 2005-002736-10 ISRCTN8734355. PMID:25553247

Minchom, A R; Saksornchai, K; Bhosle, J; Gunapala, R; Puglisi, M; Lu, S K; Nimako, K; Coward, J; Yu, K C; Bordi, P; Popat, S; O'Brien, M E R

2014-01-01

298

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

Microsoft Academic Search

The teratogenicity of antiepilepsy drug valproic acid (VPA) mostly is found in genetic and somatic levels, causing teratogenesis involving neurotubular defects (NTDs), anencephaly, lumbosacral meningomyelocele, and leg dysfunction due to spina bifida aperta. A diversity of nutraceutics have been tried to alleviate the risk of VPA-teratogenicity. The effect was varying. In order to promote the preventive prescription, to find out

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

299

Blockade of the discriminative stimulus effects of ?-hydroxybutyric acid (GHB) by the GHB receptor antagonist NCS382  

Microsoft Academic Search

The present study was designed to assess the ability of the newly synthetized, selective ?-hydroxybutyric acid (GHB) receptor antagonist, NCS-382, in blocking the discriminative stimulus effects of GHB in a T-maze, food-reinforced drug discrimination procedure. Two groups of rats were trained to run the left arm of the maze 30 min after the i.g. administration of either 300 or 700

Giancarlo Colombo; Roberta Agabio; Jacques Bourguignon; Fabio Fadda; Carla Lobina; Michel Maitre; Roberta Reali; Martine Schmitt; Gian Luigi Gessa

1995-01-01

300

Characterisation and biological activity of Glu3 amino acid substituted GIP receptor antagonists.  

PubMed

Glucose-dependent insulinotropic polypeptide (GIP) is an important gastrointestinal hormone, which regulates insulin release and glucose homeostasis, but is rapidly inactivated by enzymatic N-terminal truncation. Here we report the enzyme resistance and biological activity of several Glu(3)-substituted analogues of GIP namely; (Ala(3))GIP, (Lys(3))GIP, (Phe(3))GIP, (Trp(3))GIP and (Tyr(3))GIP. Only (Lys(3))GIP demonstrated moderately enhanced resistance to DPP-IV (p<0.05 to p<0.01) compared to native GIP. All analogues demonstrated a decreased potency in cAMP production (EC(50) 1.47 to 11.02 nM; p<0.01 to p<0.001) with (Lys(3))GIP and (Phe(3))GIP significantly inhibiting GIP-stimulated cAMP production (p<0.05). In BRIN-BD11 cells, (Lys(3))GIP, (Phe(3))GIP, (Trp(3))GIP and (Tyr(3))GIP did not stimulate insulin secretion with both (Lys(3))GIP and (Phe(3))GIP significantly inhibiting GIP-stimulated insulin secretion (p<0.05). Injection of each GIP analogue together with glucose in ob/ob mice significantly increased the glycaemic excursion compared to control (p<0.05 to p<0.001). This was associated with lack of significant insulin responses. (Ala(3))GIP, (Phe(3))GIP and (Tyr(3))GIP, when administered together with GIP, significantly reduced plasma insulin (p<0.05 to p<0.01) and impaired the glucose-lowering ability (p<0.05 to p<0.01) of the native peptide. The DPP-IV resistance and GIP antagonism observed were similar but less pronounced than (Pro(3))GIP. These data demonstrate that position 3 amino acid substitution of GIP with (Ala(3)), (Phe(3)), (Tyr(3)) or (Pro(3)) provides a new class of functional GIP receptor antagonists. PMID:17428436

Gault, Victor A; Hunter, Kerry; Irwin, Nigel; Green, Brian D; Greer, Brett; Harriott, Patrick; O'Harte, Finbarr P M; Flatt, Peter R

2007-05-15

301

A review of pharmacology of NCS-382, a putative antagonist of gamma-hydroxybutyric acid (GHB) receptor.  

PubMed

Gamma-hydroxybutyric acid (GHB), a naturally occurring metabolite of gamma-aminobutyric acid (GABA), has been postulated to act as a specific agonist of GHB receptors and as well as a weak GABA(B) receptor agonist. To date, 6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylideneacetic acid (NCS-382), a semirigid compound structurally related to GHB, is the only compound reported to be an antagonist of the GHB receptor sites. In this article we review the in vivo and in vitro pharmacological properties of NCS-382 and its interaction with GHB and GABA(B) receptors. Binding studies have demonstrated that NCS-382 is a stereoselective ligand for GHB-binding sites, with both, the high and the low component of population, showing the same distribution of GHB receptors. Indeed, this compound did not display affinity for GABA(A), GABA(B), or any other known receptors, while conflicting data have been reported as to its selective antagonist action at GHB receptor. Only a few studies have shown that NCS-382 antagonizes GHB-induced effect, but a re-evaluation of all data reported in the literature suggests that the antagonistic effect of this compound could be due to an indirect action at GABA(B) receptors. As revealed by several behavioral studies, NCS-382 fails to antagonize GHB discriminative stimuli, GHB-induced inhibition of locomotor activity and ataxia or suppression of operant responses. Moreover, it is capable of either eliciting qualitatively similar effects to those of GHB or enhancing some actions of GHB. In addition, the NCS-382-sensitive electrophysiological effects of endogenous and exogenous GHB observed in vivo have not been completely replicated in vitro. The only electrophysiological action of GHB antagonized in vitro by NCS-382 required a previous blockade of GABA(B) receptors. We concluded that NCS-382 is a good ligand but not a selective antagonist for GHB receptor. PMID:15492774

Castelli, M Paola; Pibiri, Fabio; Carboni, Giovanni; Piras, A Paola

2004-01-01

302

Narcotic antagonists in drug dependence: pilot study showing enhancement of compliance with SYN10, amino-acid precursors and enkephalinase inhibition therapy  

Microsoft Academic Search

We decided to test the hypothesis that possibly by combining a narcotic antagonist and amino-acid therapy consisting of an enkephalinase inhibitor (d-phenylalanine) and neurotransmitter precursors (l-amino- acids) to promote neuronal dopamine release might enhance compliance in methadone patients rapidly detoxified with the narcotic antagonist Trexan® (Dupont, Delaware). In this regard, Thanos et al. [J. Neurochem. 78 (2001) 1094] and associates

Thomas J. H Chen; Kenneth Blum; James T Payte; John Schoolfield; David Hopper; Mathew Stanford; Eric R Braverman

2004-01-01

303

Molecular decodification of gymnemic acids from Gymnema sylvestre. Discovery of a new class of liver X receptor antagonists.  

PubMed

The individual chemical components of commercial extract of Gymnema sylvestre, a medicinal plant used in the traditional systems of the Indian medicine for its antidiabetic and hypolipidemic properties, were isolated and evaluated for their capability to act as modulators of nuclear and membrane receptors involved in glucose and lipid homeostasis. The study disclosed for the first time that individual gymnemic acids are potent and selective antagonists for the ? isoform of LXR. Indeed the above activity was shared by the most abundant aglycone gymnemagenin (10) whereas gymnestrogenin (11) was endowed with a dual LXR?/? antagonistic profile. Deep pharmacological investigation demonstrated that gymnestrogenin, reducing the expression of SREBP1c and ABCA1 in vitro, is able to decrease lipid accumulation in HepG2 cells. The results of this study substantiate the use of G. sylvestre extract in LXR mediated dislypidemic diseases. PMID:25668616

Renga, Barbara; Festa, Carmen; De Marino, Simona; Di Micco, Simone; D'Auria, Maria Valeria; Bifulco, Giuseppe; Fiorucci, Stefano; Zampella, Angela

2015-04-01

304

Pomolic acid, triterpenoid isolated from Licania pittieri, as competitive antagonist of ADP-induced aggregation of human platelets.  

PubMed

Pomolic acid (PA), triterpenoid isolated from Licania pittieri, has previously shown a potent ability to inhibit adenosine diphosphate (ADP)- and epinephrine-induced human platelet aggregation. To investigate whether PA could be an antagonist of ADP-activated receptors of human platelets (P2Y(1) and P2Y(12)), pharmacological studies were conducted to examining its ability to modulate the platelet shape change induced by a selective P2Y(1) receptor agonist MRS2365 and also the nature of its possible interaction with ADP receptors by analyzing the characteristics of log concentration-response curves of ADP constructed in the absence and in the presence of fixed concentrations of PA, using in vitro platelet aggregation assays. PA did not interfere with the activation of P2Y(1) receptor by MRS2365 to induce platelet shape change and displayed a competitive antagonism of ADP-induced platelet aggregation, which most probably involves competition for a single binding site in platelets. The estimated equilibrium dissociate constant (K(b)) of PA as ADP receptor antagonist was 15.4±0.06nM. Together, these findings give indirect evidence for the idea that PA could be a potent competitive antagonist of P2Y(12) receptor, and open the possibility to consider it as new member of the non-nucleotide generation of antiplatelet drugs. PMID:22402243

Alvarado-Castillo, Claudia; Estrada, Omar; Carvajal, Edilmo

2012-04-15

305

Synthesis of conformationally-constrained stereospecific analogs of glutamic acid as antagonists of metabotropic receptors  

Microsoft Academic Search

Rigid analogs of ACPD have been synthesized to mimick different potential conformations of ACPD in aqueous solution. One of them, (±)-ABHD-I is a competitive antagonist at mGluR1a receptor with a KB value of 300 ?M.

Frédérique Tellier; Francine Acher; Isabelle Brabet; Jean-Philippe Pin; Joël Bockaert; Robert Azerad

1995-01-01

306

Rationale and design of the B-PROOF study, a randomized controlled trial on the effect of supplemental intake of vitamin B12 and folic acid on fracture incidence  

PubMed Central

Background Osteoporosis is a major health problem, and the economic burden is expected to rise due to an increase in life expectancy throughout the world. Current observational evidence suggests that an elevated homocysteine concentration and poor vitamin B12 and folate status are associated with an increased fracture risk. As vitamin B12 and folate intake and status play a large role in homocysteine metabolism, it is hypothesized that supplementation with these B-vitamins will reduce fracture incidence in elderly people with an elevated homocysteine concentration. Methods/Design The B-PROOF (B-Vitamins for the PRevention Of Osteoporotic Fractures) study is a randomized double-blind placebo-controlled trial. The intervention comprises a period of two years, and includes 2919 subjects, aged 65 years and older, independently living or institutionalized, with an elevated homocysteine concentration (? 12 ?mol/L). One group receives daily a tablet with 500 ?g vitamin B12 and 400 ?g folic acid and the other group receives a placebo tablet. In both tablets 15 ?g (600 IU) vitamin D is included. The primary outcome of the study is osteoporotic fractures. Measurements are performed at baseline and after two years and cover bone health i.e. bone mineral density and bone turnover markers, physical performance and physical activity including falls, nutritional intake and status, cognitive function, depression, genetics and quality of life. This large multi-center project is carried out by a consortium from the Erasmus MC (Rotterdam, the Netherlands), VUmc (Amsterdam, the Netherlands) and Wageningen University, (Wageningen, the Netherlands), the latter acting as coordinator. Discussion To our best knowledge, the B-PROOF study is the first intervention study in which the effect of vitamin B12 and folic acid supplementation on osteoporotic fractures is studied in a general elderly population. We expect the first longitudinal results of the B-PROOF intervention in the second semester of 2013. The results of this intervention will provide evidence on the efficacy of vitamin B12 and folate supplementation in the prevention of osteoporotic fractures. Trial Registration The B-PROOF study is registered with the Netherlands Trial (NTR NTR1333) and with ClinicalTrials.gov (NCT00696514). PMID:22136481

2011-01-01

307

20-125Iodo-14,15-Epoxyeicosa-5(Z)-enoic Acid: a High-Affinity Radioligand Used to Characterize the Epoxyeicosatrienoic Acid Antagonist Binding Site  

PubMed Central

Epoxyeicosatrienoic acids (EETs) are endothelium-derived metabolites of arachidonic acid. They relax vascular smooth muscle by membrane hyperpolarization. These actions are inhibited by the EET antagonist, 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EE5ZE). We synthesized 20-125iodo-14,15-EE5ZE (20-125I-14,15-EE5ZE), a radiolabeled EET antagonist, and characterized its binding to cell membranes. 14,15-EET (10?9-10?5M) caused a concentration-related relaxation of the preconstricted bovine coronary artery and phosphorylation of p38 in U937 cells that were inhibited by 20-125I-14,15-EE5ZE. Specific 20-125I-14,15-EE5ZE binding to U937 cell membranes reached equilibrium within 5 min and remained unchanged for 30 min. The binding was saturable and reversible, and it exhibited KD and Bmax values of 1.11 ± 0.13 nM and 1.13 ± 0.04 pmol/mg protein, respectively. Guanosine 5?-O-(3-thio)triphosphate (10 ?M) did not change the binding, indicating antagonist binding of the ligand. Various EETs and EET analogs (10?10-10?5M) competed for 20-125I-14,15-EE5ZE binding with an order of potency of 11,12-EET = 14,15-EET > 8,9-EET = 14,15-EE5ZE > 15-hydroxyeicosatetraenoic acid = 14,15-dihydroxyeicosatrienoic acid. 8,9-Dihydroxyeicosatrienoic acid and 11-hydroxyeicosatetraenoic acid did not compete for binding. The soluble and microsomal epoxide hydrolase inhibitors (1-cyclohexyl-3-dodecyl-urea, elaidamide, and 12-hydroxyl-elaidamide) and cytochrome P450 inhibitors (sulfaphenazole and proadifen) did not compete for the binding. However, two cytochrome P450 inhibitors, N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide (MS-PPOH) and miconazole competed for binding with Ki of 1558 and 315 nM, respectively. Miconazole and MS-PPOH, but not proadifen, inhibited 14,15-EET-induced relaxations. These findings define an EET antagonist's binding site and support the presence of an EET receptor. The inhibition of binding by some cytochrome P450 inhibitors suggests an alternative mechanism of action for these drugs and could lead to new drug candidates that target the EET binding sites. PMID:19762546

Chen, Yuenmu; Falck, John R.; Tuniki, Venugopal R.

2009-01-01

308

20-125Iodo-14,15-epoxyeicosa-5(Z)-enoic acid: a high-affinity radioligand used to characterize the epoxyeicosatrienoic acid antagonist binding site.  

PubMed

Epoxyeicosatrienoic acids (EETs) are endothelium-derived metabolites of arachidonic acid. They relax vascular smooth muscle by membrane hyperpolarization. These actions are inhibited by the EET antagonist, 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EE5ZE). We synthesized 20-(125)iodo-14,15-EE5ZE (20-(125)I-14,15-EE5ZE), a radiolabeled EET antagonist, and characterized its binding to cell membranes. 14,15-EET (10(-9)-10(-5)M) caused a concentration-related relaxation of the preconstricted bovine coronary artery and phosphorylation of p38 in U937 cells that were inhibited by 20-(125)I-14,15-EE5ZE. Specific 20-(125)I-14,15-EE5ZE binding to U937 cell membranes reached equilibrium within 5 min and remained unchanged for 30 min. The binding was saturable and reversible, and it exhibited K(D) and B(max) values of 1.11 +/- 0.13 nM and 1.13 +/- 0.04 pmol/mg protein, respectively. Guanosine 5'-O-(3-thio)triphosphate (10 muM) did not change the binding, indicating antagonist binding of the ligand. Various EETs and EET analogs (10(-10)-10(-5)M) competed for 20-(125)I-14,15-EE5ZE binding with an order of potency of 11,12-EET = 14,15-EET > 8,9-EET = 14,15-EE5ZE > 15-hydroxyeicosatetraenoic acid = 14,15-dihydroxyeicosatrienoic acid. 8,9-Dihydroxyeicosatrienoic acid and 11-hydroxyeicosatetraenoic acid did not compete for binding. The soluble and microsomal epoxide hydrolase inhibitors (1-cyclohexyl-3-dodecyl-urea, elaidamide, and 12-hydroxyl-elaidamide) and cytochrome P450 inhibitors (sulfaphenazole and proadifen) did not compete for the binding. However, two cytochrome P450 inhibitors, N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide (MS-PPOH) and miconazole competed for binding with K(i) of 1558 and 315 nM, respectively. Miconazole and MS-PPOH, but not proadifen, inhibited 14,15-EET-induced relaxations. These findings define an EET antagonist's binding site and support the presence of an EET receptor. The inhibition of binding by some cytochrome P450 inhibitors suggests an alternative mechanism of action for these drugs and could lead to new drug candidates that target the EET binding sites. PMID:19762546

Chen, Yuenmu; Falck, John R; Tuniki, Venugopal R; Campbell, William B

2009-12-01

309

(7-Benzyloxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic Acids as S1P1 Functional Antagonists.  

PubMed

S1P1 is a validated target for treatment of autoimmune disease, and functional antagonists with superior safety and pharmacokinetic properties are being sought as second generation therapeutics. We describe the discovery and optimization of (7-benzyloxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic acids as potent, centrally available, direct acting S1P1 functional antagonists, with favorable pharmacokinetic and safety properties. PMID:25516794

Buzard, Daniel J; Lopez, Luis; Moody, Jeanne; Kawasaki, Andrew; Schrader, Thomas O; Kasem, Michelle; Johnson, Ben; Zhu, Xiuwen; Thoresen, Lars; Kim, Sun Hee; Gharbaoui, Tawfik; Sengupta, Dipanjan; Calvano, Lorene; Krishnan, Ashwin; Gao, Yinghong; Semple, Graeme; Edwards, Jeff; Barden, Jeremy; Morgan, Michael; Usmani, Khawja; Chen, Chuan; Sadeque, Abu; Chen, Weichao; Christopher, Ronald J; Thatte, Jayant; Fu, Lixia; Solomon, Michelle; Whelan, Kevin; Al-Shamma, Hussien; Gatlin, Joel; Gaidarov, Ibragim; Anthony, Todd; Le, Minh; Unett, David J; Stirn, Scott; Blackburn, Anthony; Behan, Dominic P; Jones, Robert M

2014-12-11

310

Actions of excitatory amino acid agonists and antagonists on the primary afferents of the vestibular system of the axolotl (Ambystoma mexicanum)  

Microsoft Academic Search

In order to determine the nature of the transmitter in the synapse between hair cells and primary afferent fibers, both resting and evoked spike activity of vestibular system afferents were recorded. Excitatory amino acid agonists and antagonists were applied by mi- cro perfusion. Excitatory amino acid agonists consistently increased the firing rate of these afferents. The rank order in potencies

Enrique Soto; Rosario Vega

1988-01-01

311

Poly(l-lysine)-graft-folic acid-coupled poly(2-methyl-2-oxazoline) (PLL-g-PMOXA-c-FA): a bioactive copolymer for specific targeting to folate receptor-positive cancer cells.  

PubMed

In this study, we present the preparation, characterization and application of a novel bioactive copolymer poly(l-lysine)-graft-folic acid-coupled poly(2-methyl-2-oxazoline) (PLL-g-PMOXA-c-FA), which has a specific interaction with folate receptor (FR)-positive cancer cells. Glass surface immobilized with PLL-g-PMOXA-c-FA was demonstrated to be adhesive to FR-positive cancer cells (HeLa, JEG-3) while nonadhesive to FR-negative ones (MCF-7, HepG2) in 3 h. The specific interaction between conjugated FA on the substrate and FRs on the cells could hardly be inhibited unless a high concentration (5 mM) of free FA was used due to the multivalent nature of it. The FA functionality ratio of the copolymer on the substrate had a significant influence on the adhesion of HeLa cells, and our experiments revealed that the affinity of the substrate to the cells declined dramatically with the decrease of functionality ratio. This was believed to be caused by the polydispersity of PMOXA tethers, as supported by GPC and ToF-SIMS data. As a proof of concept in the application of our material, we demonstrated successful recovery of HeLa cells from mixture with MCF-7 (1:100) on the copolymer-coated glass, and our results showed that both high sensitivity (95.6 ± 13.3%) and specificity (24.3 ± 8.6%) were achieved. PMID:25581478

Chen, Yin; Cao, Wenbin; Zhou, Junli; Pidhatika, Bidhari; Xiong, Bin; Huang, Lu; Tian, Qian; Shu, Yiwei; Wen, Weijia; Hsing, I-Ming; Wu, Hongkai

2015-02-01

312

An assessment of dietary folic acid levels during gestation and lactation on reproductive and lactational performance of sows: a cooperative study. S-145 Committee on Nutritional Systems for Swine to Increase Reproductive Efficiency.  

PubMed

Crossbred female swine (n = 393) were used in a multiparity study at five experiment stations to evaluate the effects of dietary supplementation of folic acid (FA) on serum folates status and reproductive performance. The dietary treatments were a corn-soybean meal basal diet (calculated FA, .34 ppm) supplemented with 0, 1, 2, or 4 ppm FA. Experimental diets were fed continuously from a minimum of 21 d before first mating throughout the entire study. At one station, blood samples for radioimmunoassay determination of serum folates concentration were collected by vena cava puncture at mating, d 55 of gestation, d 110 of gestation, and at weaning. Stage of reproduction and dietary FA supplementation affected (P < .005) serum folates concentrations. Serum folates declined from mating to d 55, remained low at d 110, and returned to higher levels at weaning. Linear increases (P < .001) in serum folates with increasing level of dietary FA were observed at each reproductive stage. Over the course of the study, reproductive performance criteria including total pigs born, live pigs at birth and d 21, and individual pig and litter weight at birth and d 21 were not affected (P > .10) by inclusion of FA in the diet. The number of days postweaning to estrus also was not affected by FA treatment. Under the conditions of this experiment, increasing level of FA in the diet had a pronounced effect in attenuating decreased serum folates concentration during gestation but was without benefit to reproductive performance. PMID:8002452

Harper, A F; Lindemann, M D; Chiba, L I; Combs, G E; Handlin, D L; Kornegay, E T; Southern, L L

1994-09-01

313

On-line solid-phase enrichment coupled to packed reactor flow injection analysis in a green analytical procedure to determine low levels of folic acid using fluorescence detection  

PubMed Central

Background Analysis of folic acid (FA) is not an easy task because of its presence in lower concentrations, its lower stability under acidic conditions, and its sensitiveness against light and high temperature. The present study is concerned with the development and validation of an automated environmentally friendly pre-column derivatization combined by solid-phase enrichment (SPEn) to determine low levels of FA. Results Cerium (IV) trihydroxyhydroperoxide (CTH) as a packed oxidant reactor has been used for oxidative cleavage of FA into highly fluorescent product, 2-amino-4-hydroxypteridine-6-carboxylic acid. FA was injected into a carrier stream of 0.04 M phosphate buffer, pH 3.4 at a flow-rate of 0.25 mL/min. The sample zone containing the analyte was passed through the CTH reactor thermostated at 40°C, and the fluorescent product was trapped and enriched on a head of small ODS column (10 mm x 4.6 mm i.d., 5 ?m particle size). The enriched product was then back-flush eluted by column-switching from the small ODS column to the detector with a greener mobile phase consisting of ethanol and phosphate buffer (0.04M, pH 3.4) in the ratio of 5:95 (v/v). The eluent was monitored fluorimetrically at emission and excitation wavelengths of 463 and 367 nm, respectively. The calibration graph was linear over concentrations of FA in the range of 1.25-50 ng/mL, with a detection limit of 0.49 ng/mL. Conclusion A new simple and sensitive green analytical procedure including on-line pre-column derivatization combined by SPEn has been developed for the routine quality control and dosage form assay of FA at very low concentration level. The method was a powerful analytical technique that had excellent sensitivity, sufficient accuracy and required relatively simple and inexpensive instrumentation. PMID:23234331

2012-01-01

314

Effects of a histamine type 2 receptor antagonist, BMY-26539-01, on equine gastric acid secretion.  

PubMed Central

A dose-response study was undertaken of the effects of a newly developed histamine type 2 receptor antagonist, BMY-26539-01, on gastric acid secretion in 4 fasted horses. Doses of 0.1 mg/kg, 0.3 mg/kg, 0.5 mg/kg, or placebo were administered in a randomly assigned treatment sequence. Hydrogen ion concentration and pH were variable during baseline measurements in all 4 animals; however, following BMY-26539-01 administration, mean pH increased and hydrogen ion concentration decreased in a dose-related pattern. At the 0.3 mg/kg and 0.5 mg/kg dose levels, pH remained elevated for > 4 h and > 8 h, respectively. No adverse effects were observed. A significant level of 0.01 was used for all statistical methods. PMID:11227196

Orsini, J A; Spencer, P A

2001-01-01

315

Anthranilic acid derivatives: a new class of non-peptide CCK 1 receptor antagonists  

Microsoft Academic Search

Having successfully obtained new CCK1 ligands holding appropriate groups on the anthranilic acid dimer used as molecular scaffold we were interested in increasing their micromolar affinity for the CCK1 receptors by modifying the spatial relationship of the main pharmacophoric groups. Since, we have proposed simplified analogues reducing the anthranilic acid dimer to a monomer. In this stage of our research

Antonio Varnavas; Lucia Lassiani; Valentina Valenta; Federico Berti; Laura Mennuni; Francesco Makovec

2003-01-01

316

Efficient siRNA delivery and tumor accumulation mediated by ionically cross-linked folic acid-poly(ethylene glycol)-chitosan oligosaccharide lactate nanoparticles: for the potential targeted ovarian cancer gene therapy.  

PubMed

For effective ovarian cancer gene therapy, systemic administrated tumor-targeting siRNA/folic acid-poly(ethylene glycol)-chitosan oligosaccharide lactate (FA-PEG-COL) nanoparticles is vital for delivery to cancer site(s). siRNA/FA-PEG-COL nanoparticles were prepared by ionic gelation for effective FA receptor-expressing ovarian cancer cells transfection and in vivo accumulation. The chemical structure of FA-PEG-COL conjugate was characterized by MALDI-TOF-MS, FT-IR and (1)H NMR. The average size of siRNA/FA-PEG-COL nanoparticles was approximately 200 nm, and the surface charge was +8.4 mV compared to +30.5 mV with siRNA/COL nanoparticles. FA-PEG-COL nanoparticles demonstrated superior compatibility with erythrocytes in terms of degree of aggregation and haemolytic activity and also effects on cell viability was lower when compared with COL nanoparticles. FA grafting significantly facilitated the uptake of nanoparticles via receptor mediated endocytosis as demonstrated by flow cytometry. The in vitro transfection and gene knockdown efficiency of HIF-1? were superior to COL nanoparticles (76-62%, respectively) and was comparable to Lipofectamine 2000 (79%) as demonstrated by RT-qPCR and Western blot. Gene knockdown at the molecular level translated into effective inhibition of proliferation in vitro. Accumulation efficiency of FA-PEG-COL nanoparticles was investigated in BALB/c mice bearing OVK18 #2 tumor xenograft using in vivo imaging. The active targeting FA-PEG-COL nanoparticles showed significantly greater accumulation than the passive targeting COL nanoparticles. Based on the results obtained, siRNA/FA-PEG-COL nanoparticles show much potential for effective ovarian cancer treatment via gene therapy. PMID:24178005

Li, Tony Shing Chau; Yawata, Toshio; Honke, Koichi

2014-02-14

317

Cross-reactivity of acid-sensing ion channel and Na?-H? exchanger antagonists with nicotinic acetylcholine receptors.  

PubMed

Nicotinic acetylcholine receptors (nAChRs) are widely distributed throughout the mammalian central and peripheral nervous systems, where they contribute to neuronal excitability and synaptic communication. It has been reported that nAChRs are modulated by BK channels and that BK channels, in turn, are inhibited by acid-sensing ion channels (ASICs). Here we investigate the possible functional interaction between these channels in medial habenula (MHb) neurones. We report that selective antagonists of large-conductance calcium-activated potassium channels and ASIC1a channels, paxilline and psalmotoxin 1, respectively, did not induce detectable changes in nicotine-evoked currents. In contrast, the non-selective ASIC and Na(+)-H(+) exchanger (NHE1) antagonists, amiloride and its analogues, suppressed nicotine-evoked responses in MHb neurones of wild-type and ASIC2 null mice, excluding a possible involvement of ASIC2 in the nAChR inhibition by amiloride. Zoniporide, a more selective inhibitor of NHE1, reversibly inhibited ?3?4-, ?7- and ?4-containing (*) nAChRs in Xenopus oocytes and in brain slices, as well as in PS120 cells deficient in NHE1 and virally transduced with nAChRs, suggesting a generalized effect of zoniporide in most neuronal nAChR subtypes. Independently from nAChR antagonism, zoniporide profoundly blocked synaptic transmission onto MHb neurones without affecting glutamatergic and GABA receptors. Taken together, these results indicate that amiloride and zoniporide, which are clinically used to treat hypertension and cardiovascular disease, have an inhibitory effect on neuronal nAChRs when used experimentally at high doses. The possible cross-reactivity of these compounds with nAChRs in vivo will require further investigation. PMID:21911609

Santos-Torres, Julio; ?limak, Marta A; Auer, Sebastian; Ibañez-Tallon, Inés

2011-11-01

318

An arylaminopyridazine derivative of gamma-aminobutyric acid (GABA) is a selective and competitive antagonist at the GABAA receptor site.  

PubMed Central

In view of finding a new gamma-aminobutyric acid (GABA) receptor ligand we synthesized an arylaminopyridazine derivative of GABA, SR 95103 [2-(carboxy-3'-propyl)-3-amino-4-methyl-6-phenylpyridazinium chloride]. SR 95103 displaced [3H]GABA from rat brain membranes with an apparent Ki of 2.2 microM and a Hill number near 1.0. SR 95103 (1-100 microM) antagonized the GABA-mediated enhancement of [3H]diazepam binding in a concentration-dependent manner without affecting [3H]diazepam binding per se. SR 95103 competitively antagonized GABA-induced membrane depolarization in rat spinal ganglia. In all these experiments, the potency of SR 95103 was close to that of bicuculline. SR 95103 (100 microM) did not interact with a variety of central receptors--in particular the GABAB, the strychnine, and the glutamate receptors--did not inhibit Na+-dependent synaptosomal GABA uptake, and did not affect GABA-transaminase and glutamic acid decarboxylase activities. Intraperitoneally administered SR 95103 elicited clonicotonic seizures in mice (ED50 = 180 mg/kg). On the basis of these results it is postulated that St 95103 is a competitive antagonist of GABA at the GABAA receptor site. In addition to being an interesting lead structure for the search of GABA ligands, SR 95103 could also be a useful tool to investigate GABA receptor subtypes because it is freely soluble in water and chemically stable. Images PMID:2984669

Chambon, J P; Feltz, P; Heaulme, M; Restle, S; Schlichter, R; Biziere, K; Wermuth, C G

1985-01-01

319

Stapling Mimics Noncovalent Interactions of ?-Carboxyglutamates in Conantokins, Peptidic Antagonists of N-Methyl-d-Aspartic Acid Receptors*  

PubMed Central

Conantokins are short peptides derived from the venoms of marine cone snails that act as antagonists of the N-methyl-d-aspartate (NMDA) receptor family of excitatory glutamate receptors. These peptides contain ?-carboxyglutamic acid residues typically spaced at i,i+4 and/or i,i+7 intervals, which by chelating divalent cations induce and stabilize helical conformation of the peptide. Introduction of a dicarba bridge (or a staple) can covalently stabilize peptide helicity and improve its pharmacological properties. To test the hypothesis that stapling can effectively replace ?-carboxyglutamic acid residues in stabilizing the helical conformation of conantokins, we designed, synthesized, and characterized several stapled analogs of conantokin G (conG), with varying connectivities in terms of staple length and location along the face of the ?-helix. NMR studies confirmed that the ring-closing metathesis reaction yielded a single product with the Z configuration of the olefinic bond. Based on circular dichroism and molecular modeling, the stapled analogs exhibited significantly enhanced helicity compared with the native peptide in a metal-free environment. Stapling i,i+4 was benign with respect to effects on in vitro and in vivo pharmacological properties. One analog, namely conG[11–15,Si,i+4S(8)], blocked NR2B-containing NMDA receptors with IC50 = 0.7 ?m and provided significant protection in the 6-Hz psychomotor model of pharmacoresistant epilepsy in mice. Remarkably, unlike native conG, conG[11–15,Si,i+4S(8)] produced no behavioral motor toxicity. Our results extend the applications of peptide stapling to helical peptides with extracellular targets and provide a means for engineering conantokins with improved pharmacological properties. PMID:22518838

Platt, Randall J.; Han, Tiffany S.; Green, Brad R.; Smith, Misty D.; Skalicky, Jack; Gruszczy?ski, Pawe?; White, H. Steve; Olivera, Baldomero; Bulaj, Grzegorz; Gajewiak, Joanna

2012-01-01

320

A Lower Degree of PBMC L1 Methylation in Women with Lower Folate Status May Explain the MTHFR C677T Polymorphism Associated Higher Risk of CIN in the US Post Folic Acid Fortification Era  

PubMed Central

Background Studies in populations unexposed to folic acid (FA) fortification have demonstrated that MTHFR C677T polymorphism is associated with increased risk of higher grades of cervical intraepithelial neoplasia (CIN 2+). However, it is unknown whether exposure to higher folate as a result of the FA fortification program has altered the association between MTHFR C677T and risk of CIN, or the mechanisms involved with such alterations. The current study investigated the following in a FA fortified population: 1) The association between MTHFR C677T polymorphism and risk of CIN 2+; 2) The modifying effects of plasma folate concentrations on this association; and 3) The modifying effects of plasma folate on the association between the polymorphism and degree of methylation of long interspersed nucleotide elements (L1s), in peripheral blood mononuclear cell (PBMC) DNA, a documented biomarker of CIN risk. Methods The study included 457 US women diagnosed with either CIN 2+ (cases) or ? CIN 1 (non-cases). Unconditional logistic regression models were used to test the associations after adjusting for relevant risk factors for CIN. Results The 677CT/TT MTHFR genotypes were not associated with the risk of CIN 2+. Women with CT/TT genotype with lower folate, however, were more likely to be diagnosed with CIN 2+ compared to women with CT/TT genotype with higher folate (OR?=?2.41, P?=?0.030). Women with CT/TT genotype with lower folate were less likely to have a higher degree of PBMC L1 methylation compared to women with CT/TT genotype with higher folate (OR?=?0.28, P?=?0.017). Conclusions This study provides the first evidence that the MTHFR 677CT/TT genotype-associated lower degree of PBMC L1 methylation increases the risk of CIN 2+ in women in the US post-FA fortification era. Thus, even in the post-FA fortification era, not all women have adequate folate status to overcome MTHFR 677CT/TT genotype-associated lower degree of L1 methylation. PMID:25302494

Badiga, Suguna; Johanning, Gary L.; Macaluso, Maurizio; Azuero, Andres; Chambers, Michelle M.; Siddiqui, Nuzhat R.; Piyathilake, Chandrika J.

2014-01-01

321

Mercaptoacetate and fatty acids exert direct and antagonistic effects on nodose neurons via GPR40 fatty acid receptors.  

PubMed

?-mercaptoacetate (MA) is a drug known to block mitochondrial oxidation of medium- and long-chain fatty acids (FAs) and to stimulate feeding. Because MA-induced feeding is vagally dependent, it has been assumed that the feeding response is mediated by MA's antimetabolic action at a peripheral, vagally innervated site. However, MA's site of action has not yet been identified. Therefore, we used fluorescent calcium measurements in isolated neurons from rat nodose ganglia to determine whether MA has direct effects on vagal sensory neurons. We found that MA alone did not alter cytosolic calcium concentrations in nodose neurons. However, MA (60 ?M to 6 mM) significantly decreased calcium responses to both linoleic acid (LA; 10 ?M) and caprylic acid (C8; 10 ?M) in all neurons responsive to LA and C8. GW9508 (40 ?M), an agonist of the FA receptor, G protein-coupled receptor 40 (GPR40), also increased calcium levels almost exclusively in FA-responsive neurons. MA significantly inhibited this response to GW9508. MA did not inhibit calcium responses to serotonin, high K(+), or capsaicin, which do not utilize GPRs, or to CCK, which acts on a different GPR. GPR40 was detected in nodose ganglia by RT-PCR. Results suggest that FAs directly activate vagal sensory neurons via GPR40 and that MA antagonizes this effect. Thus, we propose that MA's nonmetabolic actions on GPR40 membrane receptors, expressed by multiple peripheral tissues in addition to the vagus nerve, may contribute to or mediate MA-induced stimulation of feeding. PMID:24760994

Darling, Rebecca A; Zhao, Huan; Kinch, Dallas; Li, Ai-Jun; Simasko, Steven M; Ritter, Sue

2014-07-01

322

Designing hypothesis of some 2,4 -disubstituted-phenoxy acetic acid derivatives as a Crth2 receptor antagonist: A QSAR approach  

Microsoft Academic Search

In pursuit of better CRTh2 receptor antagonist agents, 2D-QSAR, 3D- QSAR studies were performed on a series of 2,4-disubstituted-phenoxy acetic acid derivatives. The best QSAR model was selected, having correlation coefficient R = 0.904, standard error of estimation SEE = 0.456 and cross validated squared correlation coefficient Q2 = 0.739. The predictive ability of the selected model was also confirmed

Abhishek Jain; R. K. Agrawal

2009-01-01

323

A Placebo-Controlled Randomized Crossover Trial of the N-Methyl-d-Aspartic Acid Receptor Antagonist, Memantine, in Patients with Chronic Phantom Limb Pain  

Microsoft Academic Search

In the present study we investigated the effect of the N-methyl-d-aspartic acid (NMDA) receptor antagonist memantine (30 mg\\/d) on the intensity of chronic phan- tom limb pain (PLP) and cortical reorganization. In 8 patients with chronic PLP, memantine was tested in a placebo-controlled double-blinded crossover trial of 4 wk duration per trial. The intensity of PLP was rated hourly by

Katja Wiech; Ralph-Thomas Kiefer; Hubert Preissl; Christoph Braun; Klaus Unertl; Herta Flor; Niels Birbaumer

2004-01-01

324

Spina Bifida and Folic Acid Awareness  

ERIC Educational Resources Information Center

Spina bifida is the most common, permanently disabling birth defect in the United States. It is a birth defect that involves incomplete formation of the spine during the first month of pregnancy--often before a woman even knows she is pregnant. Everyday, an average of eight babies are born with spina bifida or a similar birth defect of the brain…

Exceptional Parent, 2007

2007-01-01

325

Folic Acid Helps Prevent Neural Tube Defects  

MedlinePLUS

... Stages & Populations Travelers' Health Workplace Safety & Health Features Media Sign up for Features Get Email Updates To ... live longer, healthier and more productive lives. Features Media Sign up for Features Get Email Updates To ...

326

Novel Opioid Peptide Derived Antagonists Containing (2S)-2-Methyl-3-(2,6-dimethyl-4-carbamoylphenyl)propanoic Acid [(2S)-Mdcp  

PubMed Central

A synthesis of the novel tyrosine analogue (2S)-2-methyl-3-(2,6-dimethyl-4-carbamoylphenyl)propanoic acid [(2S)-Mdcp] (15) was developed. In (2S)-Mdcp the amino- and hydroxyl groups of 2',6'-dimethyltyrosine are replaced by a methyl- and a carbamoyl group, respectively, and its substitution for Tyr1 in opioid agonist peptides resulted in compounds showing antagonism at all three opioid receptors. The cyclic peptide (2S)-Mdcp-c[D-Cys-Gly-Phe(pNO2)-D-Cys]NH2 (1) was a potent and selective ? antagonist, whereas (2S)-Mdcp-c[D-Pen-Gly-Phe(pF)-Pen]-Phe-OH (3) showed subnanomolar ? antagonist activity and extraordinary ? selectivity. PMID:18800771

Ghosh, Animesh; Luo, Jie; Liu, Chen; Weltrowska, Grazyna; Lemieux, Carole; Chung, Nga N.; Lu, Yixin; Schiller, Peter W.

2009-01-01

327

MK-801, an Excitatory Amino Acid Antagonist, Does Not Improve Neurologic Outcome Following Cardiac Arrest in Cats  

Microsoft Academic Search

Summary: The excitatory amino antagonist MK-801 was administered to cats following resuscitation from cardiac arrest to evaluate its effect on neurologic and neuropathology outcome in a clinically relevant model of complete cerebral ischemia. In 29 cats studied, cardiac arrest (ventricular fibrillation) was maintained for 18 min and resuscitation was successfully performed in 21 cats. Four animals underwent a sham arrest.

Jerry E. Fleischer; Akio Tateishi; John C. Drummond; Mark S. Scheller; Marjorie R. Grafe; Mark H. Zornow; Gary T. Shearman; Harvey M. Shapiro

1989-01-01

328

Pharmacological characterization of LY233053: A structurally novel tetrazole-substituted competitive N-methyl-D-aspartic acid antagonist with a short duration of action  

SciTech Connect

This study reports the activity of a structurally novel excitatory amino acid receptor antagonist, LY233053 (cis-(+-)-4-((2H-tetrazol-5-yl)methyl)piperidine-2-carboxylic acid), the first tetrazole-containing competitive N-methyl-D-aspartic acid (NMDA) antagonist. LY233053 potently inhibited NMDA receptor binding to rat brain membranes as shown by the in vitro displacement of (3H) CGS19755 (IC50 = 107 +/- 7 nM). No appreciable affinity in (3H)alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) or (3H)kainate binding assays was observed (IC50 values greater than 10,000 nM). In vitro NMDA receptor antagonist activity was further demonstrated by selective inhibition of NMDA-induced depolarization in cortical wedges (IC50 = 4.2 +/- 0.4 microM vs. 40 microM NMDA). LY233053 was effective after in vivo systemic administration in a number of animal models. In neonatal rats, LY233053 selectively blocked NMDA-induced convulsions (ED50 = 14.5 mg/kg i.p.) with a relatively short duration of action (2-4 hr). In pigeons, LY233053 potently antagonized (ED50 = 1.3 mg/kg i.m.) the behavioral suppressant effects of 10 mg/kg of NMDA. However, a dose of 160 mg/kg, i.m., was required to produce phencyclidine-like catalepsy in pigeons. In mice, LY233053 protected against maximal electroshock-induced seizures at lower doses (ED50 = 19.9 mg/kg i.p.) than those that impaired horizontal screen performance (ED50 = 40.9 mg/kg i.p.). Cholinergic and GABAergic neuronal degenerations after striatal infusion of NMDA were prevented by single or multiple i.p. doses of LY233053. In summary, the antagonist activity of LY233053 after systemic administration demonstrates potential therapeutic value in conditions of neuronal cell loss due to NMDA receptor excitotoxicity.

Schoepp, D.D.; Ornstein, P.L.; Leander, J.D.; Lodge, D.; Salhoff, C.R.; Zeman, S.; Zimmerman, D.M. (Eli Lilly and Company, Indianapolis, IN (USA))

1990-12-01

329

An Amino Acid Substitution Inhibits Specialist Herbivore Production of an Antagonist Effector and Recovers Insect-Induced Plant Defenses1[W][OA  

PubMed Central

Plants respond to insect herbivory through the production of biochemicals that function as either direct defenses or indirect defenses via the attraction of natural enemies. While attack by closely related insect pests can result in distinctive levels of induced plant defenses, precise biochemical mechanisms responsible for differing responses remain largely unknown. Cowpea (Vigna unguiculata) responds to Fall armyworm (Spodoptera frugiperda) herbivory through the detection of fragments of chloroplastic ATP synthase ?-subunit proteins, termed inceptin-related peptides, present in larval oral secretions (OS). In contrast to generalists like Fall armyworm, OS of the legume-specializing velvetbean caterpillar (VBC; Anticarsia gemmatalis) do not elicit ethylene production and demonstrate significantly lower induced volatile emission in direct herbivory comparisons. Unlike all other Lepidoptera OS examined, which preferentially contain inceptin (Vu-In; +ICDINGVCVDA?), VBC OS contain predominantly a C-terminal truncated peptide, Vu-In?A (+ICDINGVCVD?). Vu-In?A is both inactive and functions as a potent naturally occurring antagonist of Vu-In-induced responses. To block antagonist production, amino acid substitutions at the C terminus were screened for differences in VBC gut proteolysis. A valine-substituted peptide (Vu-In?V; +ICDINGVCVDV?) retaining full elicitor activity was found to accumulate in VBC OS. Compared with the native polypeptide, VBC that previously ingested 500 pmol of the valine-modified chloroplastic ATP synthase ?-subunit precursor elicited significantly stronger plant responses in herbivory assays. We demonstrate that a specialist herbivore minimizes the activation of defenses by converting an elicitor into an antagonist effector and identify an amino acid substitution that recovers these induced plant defenses to a level observed with generalist herbivores. PMID:23008466

Schmelz, Eric A.; Huffaker, Alisa; Carroll, Mark J.; Alborn, Hans T.; Ali, Jared G.; Teal, Peter E.A.

2012-01-01

330

Exploring a 2-naphthoic acid template for the structure-based design of P2Y14 receptor antagonist molecular probes.  

PubMed

The P2Y14 receptor (P2Y14R), one of eight P2Y G protein-coupled receptors (GPCR), is involved in inflammatory, endocrine, and hypoxic processes and is an attractive pharmaceutical target. The goal of this research is to develop high-affinity P2Y14R fluorescent probes based on the potent and highly selective antagonist 4-(4-(piperidin-4-yl)-phenyl)-7-(4-(trifluoromethyl)-phenyl)-2-naphthoic acid (6, PPTN). A model of hP2Y14R based on recent hP2Y12R X-ray structures together with simulated antagonist docking suggested that the piperidine ring is suitable for fluorophore conjugation while preserving affinity. Chain-elongated alkynyl or amino derivatives of 6 for click or amide coupling were synthesized, and their antagonist activities were measured in hP2Y14R-expressing CHO cells. Moreover, a new Alexa Fluor 488 (AF488) containing derivative 30 (MRS4174, Ki = 80 pM) exhibited exceptionally high affinity, as compared to 13 nM for the alkyne precursor 22. A flow cytometry assay employing 30 as a fluorescent probe was used to quantify specific binding to P2Y14R. Known P2Y receptor ligands inhibited binding of 30 with properties consistent with their previously established receptor selectivities and affinities. These results illustrate that potency in this series of 2-naphthoic acid derivatives can be preserved by chain functionalization, leading to highly potent fluorescent molecular probes for P2Y14R. Such conjugates will be useful tools in expanding the SAR of this receptor, which still lacks chemical diversity in its collective ligands. This approach demonstrates the predictive power of GPCR homology modeling and the relevance of newly determined X-ray structures to GPCR medicinal chemistry. PMID:25299434

Kiselev, Evgeny; Barrett, Matthew O; Katritch, Vsevolod; Paoletta, Silvia; Weitzer, Clarissa D; Brown, Kyle A; Hammes, Eva; Yin, Andrew L; Zhao, Qiang; Stevens, Raymond C; Harden, T Kendall; Jacobson, Kenneth A

2014-12-19

331

P2X7 receptor antagonists protect against N-methyl-d-aspartic acid-induced neuronal injury in the rat retina.  

PubMed

Activation of N-methyl-d-aspartic acid (NMDA) receptors followed by a large Ca(2+) influx is thought to be a mechanism of glaucoma-induced neuronal cell death. It is possible that damage-associated molecular patterns leak from injured cells, such as adenosine triphosphate, causing retinal ganglion cell death in glaucoma. In the present study, we histologically investigated whether antagonists of the P2X7 receptor protected against NMDA-induced retinal injury in the rat in vivo. Under ketamine/xylazine anesthesia, male Sprague-Dawley rats were subjected to intravitreal injection of NMDA. We used A438079 (3-(5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl)methyl pyridine) and brilliant blue G as P2X7 receptor antagonists. Upon morphometric evaluation 7 days after an intravitreal injection (200nmol/eye), NMDA-induced cell loss was apparent in the ganglion cell layer. Intravitreal A438079 (50pmol/eye) simultaneously injected with NMDA and intraperitoneal brilliant blue G (50mg/kg) administered just before the NMDA injection as well as 24 and 48h after significantly reduced cell loss. In addition, A438079 decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells 12h after NMDA injection. P2X7 receptors were immunolocalized in the ganglion cell layer and the inner and outer plexiform layers, whereas the immunopositive P2X7 receptor signal was not detected on the Iba1-positive microglial cells that infiltrated the retina 12h after NMDA injection. The present study shows that stimulation of the P2X7 receptor is involved in NMDA-induced histological damage in the rat retina in vivo. P2X7 receptor antagonists may be effective in preventing retinal diseases caused by glutamate excitotoxicity, such as glaucoma and retinal artery occlusion. PMID:25796199

Sakamoto, Kenji; Endo, Kanako; Suzuki, Taishi; Fujimura, Kyosuke; Kurauchi, Yuki; Mori, Asami; Nakahara, Tsutomu; Ishii, Kunio

2015-06-01

332

Relationship between the 19 base pair deletion polymorphism in DHFR and unmetabolized folic and in plasma and RBC folate  

Technology Transfer Automated Retrieval System (TEKTRAN)

Background: A 19 base pair (bp) deletion allele of dihydrofolate reductase (DHFR), an enzyme that makes folic acid metabolically active and reduces dihydrofolate to tetrahydrofolate to stimulate folate turnover, has been implicated in folate related health outcomes. Objective: Examine the effect ...

333

Pharmacological regulation of insulin secretion in MIN6 cells through the fatty acid receptor GPR40: identification of agonist and antagonist small molecules  

PubMed Central

Long chain fatty acids have recently been identified as agonists for the G protein-coupled receptors GPR40 and GPR120. Here, we present the first description of GW9508, a small-molecule agonist of the fatty acid receptors GPR40 and GPR120. In addition, we also describe the pharmacology of GW1100, a selective GPR40 antagonist. These molecules were used to further investigate the role of GPR40 in glucose-stimulated insulin secretion in the MIN6 mouse pancreatic ?-cell line. GW9508 and linoleic acid both stimulated intracellular Ca2+ mobilization in human embryonic kidney (HEK)293 cells expressing GPR40 (pEC50 values of 7.32±0.03 and 5.65±0.06, respectively) or GPR120 (pEC50 values of 5.46±0.09 and 5.89±0.04, respectively), but not in the parent HEK-293 cell line. GW1100 dose dependently inhibited GPR40-mediated Ca2+ elevations stimulated by GW9508 and linoleic acid (pIC50 values of 5.99±0.03 and 5.99±0.06, respectively). GW1100 had no effect on the GPR120-mediated stimulation of intracellular Ca2+ release produced by either GW9508 or linoleic acid. GW9508 dose dependently potentiated glucose-stimulated insulin secretion in MIN6 cells, but not in primary rat or mouse islets. Furthermore, GW9508 was able to potentiate the KCl-mediated increase in insulin secretion in MIN6 cells. The effects of GW9508 on insulin secretion were reversed by GW1100, while linoleic acid-stimulated insulin secretion was partially attenuated by GW1100. These results add further evidence to a link between GPR40 and the ability of fatty acids to acutely potentiate insulin secretion and demonstrate that small-molecule GPR40 agonists are glucose-sensitive insulin secretagogues. PMID:16702987

Briscoe, Celia P; Peat, Andrew J; McKeown, Stephen C; Corbett, David F; Goetz, Aaron S; Littleton, Thomas R; McCoy, David C; Kenakin, Terry P; Andrews, John L; Ammala, Carina; Fornwald, James A; Ignar, Diane M; Jenkinson, Stephen

2006-01-01

334

Effect of excitatory amino acid receptor antagonists on apomorphine-, oxytocin- and ACTH-induced penile erection and yawning in male rats.  

PubMed

The effect of excitatory amino acid receptor antagonists, (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5, 10-imine hydrogen maleate ((+)-MK-801), (+/-)-3-(2-carboxy-piperazin-4-yl)-propyl-1-phosphonic acid (CPP), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and (+/-)-2-amino-4-phosphonobutanoic acid (AP-4), on penile erection and yawning induced by subcutaneous apomorphine (80 micrograms/kg), intracerebroventricular (i.c.v.) oxytocin (30 ng) and adrenocorticotropin (ACTH)-(1-24) (10 micrograms) was studied in male rats. Intraperitoneal (0.1-0.4 mg/kg) and i.c.v. (10-50 micrograms) (+)-MK-801 prevented dose dependently the penile erection and yawning induced by the three drugs. The (+)-MK-801 effect coincided with the appearance of head weaving, body rolling, hyperlocomotion and ataxia. Haloperidol (0.5 mg/kg i.p.) antagonized the prevention by (+)-MK-801 of oxytocin responses. Penile erection but not yawning was also prevented by high, but not low doses of CPP and CNQX, which impaired motor performance, AP-4 was ineffective at all doses tested. The above compounds were ineffective when injected into the paraventricular nucleus of the hypothalamus, the brain area where apomorphine and oxytocin act to induce penile erection and yawning. The results suggest that excitatory amino acid transmission is not involved in the expression of penile erection and yawning induced by the above compounds. PMID:1358647

Melis, M R; Stancampiano, R; Argiolas, A

1992-09-10

335

Revaprazan, a novel acid pump antagonist, exerts anti-inflammatory action against Helicobacter pylori-induced COX-2 expression by inactivating Akt signaling  

PubMed Central

Chronic gastric inflammation developing after Helicobacter pylori (H. pylori) infection is responsible for either dyspeptic symptom relevant to gastritis/peptic ulcer or gastric tumorigenesis, in which acid suppressants, especially proton pump inhibitors (PPIs), play role in relieving dyspepsia as well as the eradication regimen. Among several mediators engaged in propagating gastric inflammation after H. pylori infection, cyclooxygenase-2 (COX-2) might be the principal one, and several prescriptions have been made for decreasing the COX-2 levels. Multiple line of evidence are available for anti-inflammatory action of PPIs beyond acid suppression, but revaprazan, a novel acid pump antagonist launched in clinic, has also been suggested to exert significant anti-inflammatory actions as much as PPI. In the current study, we hypothesized that revaprazan could regulate H. pylori-driven COX-2 expression as one of its anti-inflammatory pharmacological actions. The changes of gastric COX-2 expression as well as responsible transcription factors were measured after H. pylori infection in the presence or absence of revaprazan. Infection of AGS cells with H. pylori induced significant up-regulation of COX-2 in time- and concentration-dependent manners, which was mediated by Akt phosphorylation. Revaprazan treatment significantly inhibited IkappaB-alpha degradation as well as Akt inactivation, resulting in attenuation of H. pylori-induced COX-2 expression. Additional rescuing action of revaprazan against H. pylori-induced cytotoxicity was noted. In conclusion, revaprazan imposed significant anti-inflammatory actions on H. pylori infection beyond acid suppression. PMID:22962522

Lee, Jeong-Sang; Cho, Ji-Yoon; Song, Heup; Kim, Eun-Hee; Hahm, Ki-Baik

2012-01-01

336

Lipoteichoic Acid Acts as an Antagonist and an Agonist of Lipopolysaccharide on Human Gingival Fibroblasts and Monocytes in a CD14-Dependent Manner  

PubMed Central

CD14 has been implicated as a receptor of lipoteichoic acid (LTA) and other bacterial components as well as lipopolysaccharide (LPS). Since the structures of LTAs from various gram-positive bacteria are heterogeneous, we analyzed the effects of LTAs on the secretion of interleukin-8 (IL-8) by high- and low-CD14-expressing (CD14high and CD14low) human gingival fibroblasts (HGF). While Bacillus subtilis LTA had an IL-8-inducing effect on CD14high HGF which was considerably weaker than that of LPS, Streptococcus sanguis and Streptococcus mutans LTAs had practically no effect on the cells. B. subtilis LTA had only a weak effect on CD14low HGF, as did LPS. S. sanguis and S. mutans LTAs at a 1,000-fold excess each completely inhibited the IL-8-inducing activities of both LPS and a synthetic lipid A on CD14high HGF. The effect of LPS was also inhibited by the presence of an LPS antagonist, synthetic lipid A precursor IVA (LA-14-PP), with a 100-fold higher potency than S. sanguis and S. mutans LTAs and by anti-CD14 monoclonal antibody (MAb). S. sanguis and S. mutans LTAs, LA-14-PP, and anti-CD14 MAb had no significant effect on phorbol myristate acetate-stimulated IL-8 secretion by HGF. These LTAs also inhibited the IL-8-inducing activity of B. subtilis LTA on CD14high HGF, as did LA-14-PP and anti-CD14 MAb. The antagonistic and agonistic functions of LTAs were also observed with human monocytes. Binding of fluorolabeled LPS to human monocytes was inhibited by S. sanguis LTA, although the inhibition was 100 times weaker than that of LPS itself, and anti-CD14 MAb inhibited fluorolabeled LPS and S. sanguis LTA binding. Binding of LTAs to CD14 was also observed with nondenaturing polyacrylamide gel electrophoresis. These results indicate that LTAs act as antagonists or agonists via a CD14-dependent mechanism, probably due to the heterogeneous structure of LTAs, and that an antagonistic LTA might be a useful agent for suppressing the periodontal disease caused by gram-negative bacteria. PMID:10084995

Sugawara, Shunji; Arakaki, Rieko; Rikiishi, Hidemi; Takada, Haruhiko

1999-01-01

337

Narcotic antagonists in drug dependence: pilot study showing enhancement of compliance with SYN-10, amino-acid precursors and enkephalinase inhibition therapy.  

PubMed

We decided to test the hypothesis that possibly by combining a narcotic antagonist and amino-acid therapy consisting of an enkephalinase inhibitor (D-phenylalanine) and neurotransmitter precursors (L-amino- acids) to promote neuronal dopamine release might enhance compliance in methadone patients rapidly detoxified with the narcotic antagonist Trexan (Dupont, Delaware). In this regard, Thanos et al. [J. Neurochem. 78 (2001) 1094] and associates found increases in the dopamine D2 receptors (DRD2) via adenoviral vector delivery of the DRD2 gene into the nucleus accumbens, significantly reduced both ethanol preference (43%) and alcohol intake (64%) of ethanol preferring rats, which recovered as the DRD2, returned to baseline levels. This DRD2 overexpression similarly produced significant reductions in ethanol non-preferring rats, in both alcohol preference (16%) and alcohol intake (75%). This work further suggests that high levels of DRD2 may be protective against alcohol abuse [JAMA 263 (1990) 2055; Arch, Gen. Psychiatr. 48 (1991) 648]. The DRD2 A1 allele has also been shown to associate with heroin addicts in a number of studies. In addition, other dopaminergic receptor gene polymorphisms have also associated with opioid dependence. For example, Kotler et al. [Mol. Phychiatr. 3 (1997) 251] showed that the 7 repeat allele of the DRD4 receptor is significantly overpresented in the opioid-dependent cohort and confers a relative risk of 2.46. This has been confirmed by Li et al. [Mol. Psychiatry 2 (1997) 413] for both the 5 and 7 repeat alleles in Han Chinese case control sample of heroin addicts. Similarly Duaux et al. [Mol. Psychiatry 3 (1998) 333] in French Heroin addicts, found a significant association with homozygotes alleles of the DRD3-Bal 1. A study from NIAAA, provided evidence which strongly suggests that DRD2 is a susceptibility gene for substance abusers across multiple populations (2003). Moreover, there are a number of studies utilizing amino-acid and enkephalinase inhibition therapy showing reduction of alcohol, opiate, cocaine and sugar craving behavior in human trials (see Table 1). Over the last decade, a new rapid method to detoxify either methadone or heroin addicts utilizing Trexan sparked interest in many treatment centers throughout the United States, Canada, as well as many countries on a worldwide basis. In using the combination of Trexan and amino-acids, results were dramatic in terms of significantly enhancing compliance to continue taking Trexan. The average number of days of compliance calculated on 1000 patients, without amino-acid therapy, using this rapid detoxification method is only 37 days. In contrast, the 12 subjects tested, receiving both the Trexan and amino-acid therapy was relapse-free or reported taking the combination for an average of 262 days (p < 0.0001F). Thus coupling amino-acid therapy and enkephalinase inhibition while blocking the delta-receptors with a pure narcotic antagonist may be quite promising as a novel method to induce rapid detox in chronic methadone patients. This may also have important ramifications in the treatment of both opiate and alcohol-dependent individuals, especially as a relapse prevention tool. It may also be interesting too further test this hypothesis with the sublingual combination of the partial opiate mu receptor agonist buprenorphrine. PMID:15288384

Chen, Thomas J H; Blum, Kenneth; Payte, James T; Schoolfield, John; Hopper, David; Stanford, Mathew; Braverman, Eric R

2004-01-01

338

Antagonistic Interaction between Abscisic Acid and Jasmonate-Ethylene Signaling Pathways Modulates Defense Gene Expression and Disease Resistance in Arabidopsis  

Microsoft Academic Search

The plant hormones abscisic acid (ABA), jasmonic acid (JA), and ethylene are involved in diverse plant processes, including the regulation of gene expression during adaptive responses to abiotic and biotic stresses. Previously, ABA has been implicated in enhancing disease susceptibility in various plant species, but currently very little is known about the molecular mechanisms underlying this phenomenon. In this study,

Jonathan P. Anderson; Ellet Badruzsaufari; Peer M. Schenk; John M. Manners; Olivia J. Desmond; Christina Ehlert; Donald J. Maclean; Paul R. Ebert; Kemal Kazana

2004-01-01

339

Folic acid-enhanced synergy for the combination of trimetrexate plus the glycinamide ribonucleotide formyltransferase inhibitor 4-[2-(2-amino-4-oxo-4,6,7,8-tetrahydro-3H-pyrimidino[5,4,6][1,4]thiazin -6-yl)-(S)-ethyl]-2,5-thienoylamino-L-glutamic acid (AG2034): comparison across sensitive and resistant human tumor cell lines.  

PubMed

Folic acid (PteGlu)-enhanced intense synergy has been observed between nonpolyglutamylatable dihydrofolate reductase (DHFR) inhibitors and polyglutamylatable inhibitors of other folate-requiring enzymes, such as glycinamide ribonucleotide formyltransferase (GARFT) and thymidylate synthase. Since this phenomenon is potentially therapeutically useful, we explored its universality by examining the combined action of a DHFR inhibitor, trimetrexate (TMQ), with a GARFT inhibitor, 4-[2-(2-amino-4-oxo-4,6,7,8-tetrahydro-3H-pyrimidino[5,4,6][1,4]++ +thiazin-6-yl)-(S)-ethyl]-2,5-thienoylamino-L-glutamic acid (AG2034), in eight human cultured cell lines. Using a 96-well plate cell growth inhibition assay, four ileocecal adenocarcinoma cell lines [HCT-8, HCT-8/DW2 (Tomudex-resistant), HCT-8/DF2 (Tomudex-/FdUrd-resistant), and HCT-8/50 (adapted to 50 nM PteGlu)], three head and neck carcinoma cell lines [A253, FaDu, and Hep-2/500 (FdUrd-resistant)], and a non-small cell lung carcinoma cell line [H460] were treated for 96 hr with TMQ + AG2034 in the presence of 23 or 40 microM PteGlu. Cell growth was measured with the sulforhodamine B assay at the end of this period. Drug interactions were assessed by fitting a 7-parameter model including a synergism parameter, alpha, to data with weighted nonlinear regression. Isobologram analysis was also applied. At 23 microM PteGlu, cells exhibited similar intensities of Loewe synergy for the combination of TMQ + AG2034. Loewe synergy was abolished in HCT-8/50 cells cultured and studied in 50 nM PteGlu. At 40 microM PteGlu, the intensity of the combined action in all cell lines was increased However, the most intense Loewe synergy was seen with HCT-8, HCT-8/DF2, H460, FaDu, A253, and Hep-2/500 cells, whereas the HCT-8/50 subculture showed less of the phenomenon, and PteGlu enhancement was the least with HCT-8/DW2, a subline deficient in folylpolyglutamate synthetase (FPGS). The universality of the PteGlu-enhanced intense synergy phenomenon is suggested. Impaired FPGS activity and low-folate adaptation prior to treatment significantly lessen the degree of PteGlu enhancement. PMID:9952321

Faessel, H M; Slocum, H K; Rustum, Y M; Greco, W R

1999-03-01

340

Dickkopf-1, the Wnt antagonist, is induced by acidic pH and mediates epithelial cellular senescence in human reflux esophagitis  

PubMed Central

Squamous esophageal epithelium adapts to acid reflux-mediated injury by proliferation and differentiation via signal transduction pathways. Induction of the Wnt antagonist Dickkopf-1 (Dkk1) is involved in tissue repair during inflammation and cellular injury. In this study, we aimed to identify the biological role of Dkk1 in human reflux esophagitis with respect to cell growth and regulation of Wnt signaling. Esophageal biopsies from reflux-esophagitis patients (n = 15) and healthy individuals (n = 10) were characterized in terms of Dkk1 expression. The role of Dkk1 in response to acid-mediated epithelial injury was analyzed by cellular assays in vitro utilizing squamous esophageal epithelial cell lines (EPC1-hTERT, EPC2-hTERT, and HEEC). Dkk1 was significantly overexpressed in human reflux-esophagitis tissue compared with healthy esophageal mucosa at transcriptional and translational levels. After acute and chronic acid (pH 4) exposure, esophageal squamous epithelial cell lines expressed and secreted high levels of Dkk1 in response to stress-associated DNA injury. High extracellular levels of human recombinant Dkk1 inhibited epithelial cell growth and induced cellular senescence in vitro, as demonstrated by reduced cell proliferation, G0/G1 cell cycle arrest, elevated senescence-associated ?-galactosidase activity, and upregulation of p16. Acid pulsing induced Dkk1-mediated senescence, which was directly linked to the ability of Dkk1 to antagonize the canonical Wnt/?-catenin signaling. In healthy esophageal mucosa, Dkk1 expression was associated with low expression of transcriptionally active ?-catenin, while in reflux-esophagitis tissue, Dkk1 overexpression correlated with increased senescence-associated ?-galactosidase activity and p16 upregulation. The data indicate that, in human reflux esophagitis, Dkk1 functions as a secreted growth inhibitor by suppressing Wnt/?-catenin signaling and promoting cellular senescence. These findings suggest a significant role for Dkk1 and cellular senescence in esophageal tissue homeostasis during reflux esophagitis. PMID:24481601

Lyros, Orestis; Rafiee, Parvaneh; Nie, Linghui; Medda, Rituparna; Jovanovic, Nebojsa; Schmidt, Jamie; Mackinnon, Alexander; Venu, Nanda

2014-01-01

341

Dickkopf-1, the Wnt antagonist, is induced by acidic pH and mediates epithelial cellular senescence in human reflux esophagitis.  

PubMed

Squamous esophageal epithelium adapts to acid reflux-mediated injury by proliferation and differentiation via signal transduction pathways. Induction of the Wnt antagonist Dickkopf-1 (Dkk1) is involved in tissue repair during inflammation and cellular injury. In this study, we aimed to identify the biological role of Dkk1 in human reflux esophagitis with respect to cell growth and regulation of Wnt signaling. Esophageal biopsies from reflux-esophagitis patients (n = 15) and healthy individuals (n = 10) were characterized in terms of Dkk1 expression. The role of Dkk1 in response to acid-mediated epithelial injury was analyzed by cellular assays in vitro utilizing squamous esophageal epithelial cell lines (EPC1-hTERT, EPC2-hTERT, and HEEC). Dkk1 was significantly overexpressed in human reflux-esophagitis tissue compared with healthy esophageal mucosa at transcriptional and translational levels. After acute and chronic acid (pH 4) exposure, esophageal squamous epithelial cell lines expressed and secreted high levels of Dkk1 in response to stress-associated DNA injury. High extracellular levels of human recombinant Dkk1 inhibited epithelial cell growth and induced cellular senescence in vitro, as demonstrated by reduced cell proliferation, G0/G1 cell cycle arrest, elevated senescence-associated ?-galactosidase activity, and upregulation of p16. Acid pulsing induced Dkk1-mediated senescence, which was directly linked to the ability of Dkk1 to antagonize the canonical Wnt/?-catenin signaling. In healthy esophageal mucosa, Dkk1 expression was associated with low expression of transcriptionally active ?-catenin, while in reflux-esophagitis tissue, Dkk1 overexpression correlated with increased senescence-associated ?-galactosidase activity and p16 upregulation. The data indicate that, in human reflux esophagitis, Dkk1 functions as a secreted growth inhibitor by suppressing Wnt/?-catenin signaling and promoting cellular senescence. These findings suggest a significant role for Dkk1 and cellular senescence in esophageal tissue homeostasis during reflux esophagitis. PMID:24481601

Lyros, Orestis; Rafiee, Parvaneh; Nie, Linghui; Medda, Rituparna; Jovanovic, Nebojsa; Schmidt, Jamie; Mackinnon, Alexander; Venu, Nanda; Shaker, Reza

2014-04-01

342

Dual orexin receptor antagonists show distinct effects on locomotor performance, ethanol interaction and sleep architecture relative to gamma-aminobutyric acid-A receptor modulators  

PubMed Central

Dual orexin receptor antagonists (DORAs) are a potential treatment for insomnia that function by blocking both the orexin 1 and orexin 2 receptors. The objective of the current study was to further confirm the impact of therapeutic mechanisms targeting insomnia on locomotor coordination and ethanol interaction using DORAs and gamma-aminobutyric acid (GABA)-A receptor modulators of distinct chemical structure and pharmacological properties in the context of sleep-promoting potential. The current study compared rat motor co-ordination after administration of DORAs, DORA-12 and almorexant, and GABA-A receptor modulators, zolpidem, eszopiclone, and diazepam, alone or each in combination with ethanol. Motor performance was assessed by measuring time spent walking on a rotarod apparatus. Zolpidem, eszopiclone and diazepam [0.3–30 mg/kg administered orally (PO)] impaired rotarod performance in a dose-dependent manner. Furthermore, all three GABA-A receptor modulators potentiated ethanol- (0.25–1.5 g/kg) induced impairment on the rotarod. By contrast, neither DORA-12 (10–100 mg/kg, PO) nor almorexant (30–300 mg/kg, PO) impaired motor performance alone or in combination with ethanol. In addition, distinct differences in sleep architecture were observed between ethanol, GABA-A receptor modulators (zolpidem, eszopiclone, and diazepam) and DORA-12 in electroencephalogram studies in rats. These findings provide further evidence that orexin receptor antagonists have an improved motor side-effect profile compared with currently available sleep-promoting agents based on preclinical data and strengthen the rationale for further evaluation of these agents in clinical development. PMID:24399926

Ramirez, Andres D.; Gotter, Anthony L.; Fox, Steven V.; Tannenbaum, Pamela L.; Yao, Lihang; Tye, Spencer J.; McDonald, Terrence; Brunner, Joseph; Garson, Susan L.; Reiss, Duane R.; Kuduk, Scott D.; Coleman, Paul J.; Uslaner, Jason M.; Hodgson, Robert; Browne, Susan E.; Renger, John J.; Winrow, Christopher J.

2013-01-01

343

Succession of dominant and antagonistic lactic acid bacteria in fermented cucumber: Insights from a PCR-based approach  

Microsoft Academic Search

The goal of the investigation was to study the succession of major groups of lactic acid bacteria (LAB) and their antagonism in salt-fermented cucumber using PCR. In a direct detection method as well as a short enrichment process, PCR enabled detection of Leuconostoc and Lactobacillus during early hours of fermentation. Subsequently, Lactobacillus and Pediococcus emerged as the dominant genera. Nucleic

Atul Kumar Singh; Aiyagari Ramesh

2008-01-01

344

Molecular basis determining inhibition/activation of nociceptive receptor TRPA1 protein: a single amino acid dictates species-specific actions of the most potent mammalian TRPA1 antagonist.  

PubMed

The transient receptor potential ankyrin 1 (TRPA1) is a Ca(2+)-permeable, nonselective cation channel mainly expressed in a subset of nociceptive neurons. TRPA1 functions as a cellular sensor detecting mechanical, chemical, and thermal stimuli. Because TRPA1 is considered to be a key player in nociception and inflammatory pain, TRPA1 antagonists have been developed as analgesic agents. Recently, by utilizing species differences, we identified the molecular basis of the antagonistic action of A967079, one of the most potent mammalian TRPA1 antagonists. Here, we show a unique effect of A967079 on TRPA1 from diverse vertebrate species, i.e. it acts as an agonist but not as an antagonist for chicken and frog TRPA1s. By characterizing chimeric channels of human and chicken TRPA1s, as well as point mutants, we found that a single specific amino acid residue located within the putative fifth transmembrane domain was involved in not only the stimulatory but also the inhibitory actions of A967079. AP18, structurally related to A967079, exerted similar pharmacological properties to A967079. Our findings and previous reports on species differences in the sensitivity to TRPA1 antagonists supply useful information in the search for novel analgesic medicines targeting TRPA1. PMID:25271161

Banzawa, Nagako; Saito, Shigeru; Imagawa, Toshiaki; Kashio, Makiko; Takahashi, Kenji; Tominaga, Makoto; Ohta, Toshio

2014-11-14

345

Zhankuic acid A isolated from Taiwanofungus camphoratus is a novel selective TLR4/MD-2 antagonist with anti-inflammatory properties.  

PubMed

TLR4, a membrane receptor that functions in complex with its accessory protein myeloid differentiation factor-2 (MD-2), is a therapeutic target for bacterial infections. Taiwanofungus camphoratus is highly valued as a medicinal mushroom for cancer, hypertension, and inflammation in traditional medicine. Zhankuic acid A (ZAA) is the major pharmacologically active compound of T. camphoratus. The mechanism of action of T. camphoratus or ZAA has not been fully elucidated. We analyzed the structure of human TLR4/MD-2 complex with ZAA by X-score and HotLig modeling approaches. Two Abs against MD-2 were used to verify the MD-2/ZAA interaction. The inflammation and survival of the mice pretreated with ZAA and injected with LPS were monitored. The modeling structure shows that ZAA binds the MD-2 hydrophobic pocket exclusively via specific molecular recognition; the contact interface is dominated by hydrophobic interactions. Binding of ZAA to MD-2 reduced Ab recognition to native MD-2, similar to the effect of LPS binding. Furthermore, ZAA significantly ameliorated LPS-induced endotoxemia and Salmonella-induced diarrhea in mice. Our results suggest that ZAA, which can compete with LPS for binding to MD-2 as a TLR4/MD-2 antagonist, may be a potential therapeutic agent for gram-negative bacterial infections. PMID:24532584

Chen, Yu-Fon; Shiau, Ai-Li; Wang, Sheng-Hung; Yang, Jai-Sing; Chang, Sue-Joan; Wu, Chao-Liang; Wu, Tian-Shung

2014-03-15

346

Zhankuic Acid A Isolated from Taiwanofungus camphoratus Is a Novel Selective TLR4/MD-2 Antagonist with Anti-Inflammatory Properties  

PubMed Central

TLR4, a membrane receptor that functions in complex with its accessory protein myeloid differentiation factor-2 (MD-2), is a therapeutic target for bacterial infections. Taiwanofungus camphoratus is highly valued as a medicinal mushroom for cancer, hypertension, and inflammation in traditional medicine. Zhankuic acid A (ZAA) is the major pharmacologically active compound of T. camphoratus. The mechanism of action of T. camphoratus or ZAA has not been fully elucidated. We analyzed the structure of human TLR4/MD-2 complex with ZAA by X-score and HotLig modeling approaches. Two Abs against MD-2 were used to verify the MD-2/ZAA interaction. The inflammation and survival of the mice pretreated with ZAA and injected with LPS were monitored. The modeling structure shows that ZAA binds the MD-2 hydrophobic pocket exclusively via specific molecular recognition; the contact interface is dominated by hydrophobic interactions. Binding of ZAA to MD-2 reduced Ab recognition to native MD-2, similar to the effect of LPS binding. Furthermore, ZAA significantly ameliorated LPS-induced endotoxemia and Salmonella-induced diarrhea in mice. Our results suggest that ZAA, which can compete with LPS for binding to MD-2 as a TLR4/MD-2 antagonist, may be a potential therapeutic agent for gram-negative bacterial infections. PMID:24532584

Chen, Yu-Fon; Shiau, Ai-Li; Wang, Sheng-Hung; Yang, Jai-Sing; Chang, Sue-Joan

2014-01-01

347

Antagonistic roles of abscisic acid and cytokinin during response to nitrogen depletion in oleaginous microalga Nannochloropsis oceanica expand the evolutionary breadth of phytohormone function.  

PubMed

The origin of phytohormones is poorly understood, and their physiological roles in microalgae remain elusive. Genome comparison of photosynthetic autotrophic eukaryotes has revealed that the biosynthetic pathways of abscisic acid (ABA) and cytokinins (CKs) emerged in unicellular algae. While ABA and CK degradation mechanisms emerged broadly in algal lineages, complete vascular plant-type conjugation pathways emerged prior to the rise of Streptophyta. In microalgae, a complete set of proteins from the canonical ABA and CK sensing and signaling pathways is not essential, but individual components are present, suggesting stepwise recruitment of phytohormone signaling components. In the oleaginous eustigmatophyte Nannochloropsis oceanica IMET1, UHPLC-MS/MS detected a wide array of plant hormones, despite a phytohormone profile that is very distinct from that of flowering plants. Time-series transcriptional analysis during nitrogen depletion revealed activation of the ABA biosynthetic pathway and antagonistic transcription of CK biosynthetic genes. Correspondingly, the ABA level increases while the dominant bioactive CK forms decrease. Moreover, exogenous CKs stimulate cell-cycle progression while exogenous ABA acts as both an algal growth repressor and a positive regulator in response to stresses. The presence of such functional flowering plant-like phytohormone signaling systems in Nannochloropsis sp. suggests a much earlier origin of phytohormone biosynthesis and degradation than previously believed, and supports the presence in microalgae of as yet unknown conjugation and sensing/signaling systems that may be exploited for microalgal feedstock development. PMID:25041627

Lu, Yandu; Tarkowská, Danuše; Ture?ková, Veronika; Luo, Tingwei; Xin, Yi; Li, Jing; Wang, Qintao; Jiao, Nianzhi; Strnad, Miroslav; Xu, Jian

2014-10-01

348

Biocontrol of blue and gray mold diseases of pear fruit by integration of antagonistic yeast with salicylic acid.  

PubMed

This study was conducted to evaluate the efficacy of the biocontrol yeast Cryptococcus laurentii and salicylic acid (SA) in suppressing the blue and gray mould rots in pear fruit and to explore possible mode of action involved. Our results showed that the combined treatment of pear fruit with C. laurentii with SA at 100 microg ml(-1) resulted in a remarkably improved control of Penicillium expansum and Botrytis cinerea infections, including the pre-inoculated P. expansum, in comparison with the application of C. laurentii or SA alone. The biocontrol yeast C. laurentii proliferated rapidly within the first 24 h of incubation in pear fruit wounds. Although SA at 100 microg ml(-1) neither affected the population growth of C. laurentii nor directly inhibited the blue mold when the inoculation concentrations of P. expansum were above 5 x 10(2) spore per ml in vivo, it induced the fruit resistance to the blue and gray mold rots when the time interval between SA treatment and pathogens inoculation was more than 48 h, being associated with a rapid and strong activation of the peroxidase activity in pear fruit. Thus we assume that SA may be regarded as a secondary defense line in a combination of C. laurentii and SA, which could reinforce the biocontrol efficacy of C. laurentii by induction of the fruit natural resistance. PMID:17428566

Yu, Ting; Chen, Jishuang; Chen, Rongle; Huang, Bin; Liu, Donghong; Zheng, Xiaodong

2007-05-30

349

Comparison of the antithrombotic effects and bleeding risk of fractionated aurin tricarboxylic acid and the GPIIb/IIIa antagonist GR144053 in a hamster model of stenosis.  

PubMed

The present study compared the antithrombotic properties of fractionated aurin tricarboxylic acid (ATA), an inhibitor of platelet glycoprotein (GP) Ib, and GR144053, a GPIIb/IIIa antagonist, in a hamster model of stenosis. Endothelial cell injury in the hamster carotid artery was achieved by a 2F modified catheter. Arterial blood flow in the control groups was interrupted 5.4+/-0.9 minutes after the injury. When ATA (0.01, 0.03, 0.1, 0.3, and 1.0 mg/kg per hour) or GR144053 (0.1, 0.3, and 1.0 mg/kg per hour) were continuously infused intravenously, the time elapse before the vessel completely occluded was prolonged in a dose-dependent manner. However, all arteries in the ATA-treated groups ultimately occluded during the observation period even if the aggregation of platelets ex vivo and induced by botrocetin was completely inhibited. When either ATA (0.1 mg/kg per hour) or GR144053 (0.3 mg/kg per hour) were infused via an implanted osmotic pump together with tissue-type plasminogen activator (tPA), late patency of the reperfused artery was improved compared to that of arteries treated with TPA alone. However, the cyclic reflow pattern after reperfusion on days 0 and 1 was not reduced by the ATA treatment. The bleeding time was significantly prolonged when either ATA or GT144053 was coadministered with tPA. The treatment with ATA showed an especially marked prolongation of the bleeding time. In conclusion, both inhibition of platelet activation by ATA or GR144053 prevent arterial thrombosis and enhance the thrombolytic effect of tPA, but GR144053 was more protective in its antithrombotic effect and more effective during thrombolytic therapy than ATA. PMID:10403686

Ito, T; Matsuno, H; Kozawa, O; Niwa, M; Sakai, N; Uematsu, T

1999-07-01

350

Synthesis and separation of the enantiomers of the Neuropeptide S receptor antagonist (9R/S)-3-Oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide (SHA 68)  

PubMed Central

This study reports the synthesis, chromatographic separation and pharmacological evaluation of the two enantiors of the neuropeptide S receptor (NPSR) antagonist (9R/S)-3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide (SHA 68). The (9R)-3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide (compound 10) and (9S)-3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide (compound 10a) were synthesized and their purity assessed by chiral chromatography. The absolute configuration of the enantiomer 10 has been assigned from the crystal structure of the corresponding (S)-phenyl ethyl amine derivative 8. Calcium mobilization studies performed on cells expressing the recombinant NPSR demonstrated that compound 10 is the active enantiomer while the contribution of 10a to the NPSR antagonist properties of the racemic mixture is negligible. PMID:21466221

Trapella, Claudio; Pela', Michela; Zoppo, Luisa Del; Calo', Girolamo; Camarda, Valeria; Ruzza, Chiara; Cavazzini, Alberto; Costa, Valentina; Bertolasi, Valerio; Reinscheid, Rainer K.; Salvadori, Severo; Guerrini, Remo

2011-01-01

351

Leukotriene receptor antagonist therapy  

PubMed Central

Leukotriene receptor antagonists (LTRA) are a new class of drugs for asthma treatment, available in tablet form. Their unique mechanism of action results in a combination of both bronchodilator and anti-inflammatory effects. While their optimal place in asthma management is still under review, LTRA represent an important advance in asthma pharmacotherapy.???Keywords: leukotriene receptor antagonist; asthma; montelukast; zafirlukast PMID:11085767

Dempsey, O

2000-01-01

352

Folic acid, homocysteine and cardiovascular disease: Are the dots connecting?  

Technology Transfer Automated Retrieval System (TEKTRAN)

For many decades, atherosclerosis research has been dominated by the lipid hypothesis. Even when new concepts were brought to the table (i.e., oxidation hypothesis); efforts were made to fit them into the lipid context (i.e., oxidized LDL). This dominance provided the right environment for the devel...

353

21 CFR 172.345 - Folic acid (folacin).  

Code of Federal Regulations, 2010 CFR

...Applied Nutrition's Library, Food and Drug Administration, 5100 Paint Branch...section 401 of the Federal Food, Drug, and Cosmetic Act (the act) when...defined in section 5(b)(3) of the Orphan Drug Act (21 U.S.C....

2010-04-01

354

The pathogenesis of folic acid deficiency in man  

Microsoft Academic Search

ACH year in this lecture we honour the name of Dr. Robert Graves, a physician, writer and philosopher of the early nineteenth century. The lustre his name has added to Irish medicine throughout the world needs no elaboration. I must however confess that I was pleasantly surprised to learn of the approbation with which he was received by his contemporary

D. G. Weir

1974-01-01

355

Folates and Folic Acid: From Fundamental Research Toward Sustainable Health  

Microsoft Academic Search

Folates are of paramount importance in one-carbon metabolism of most organisms. Plants and microorganisms are able to synthesize folates de novo, making them the main dietary source for humans and animals, which are dependent on food or feed supplies for folates. Folate deficiency is an increasing problem in the developing, as well as in the developed regions of the world,

Dieter Blancquaert; Sergei Storozhenko; Karen Loizeau; Hans De Steur; Veerle De Brouwer; Jacques Viaene; Stéphane Ravanel; Fabrice Rébeillé; Willy Lambert; Dominique Van Der Straeten

2010-01-01

356

Uracil misincorporation into DNA and folic acid supplementation  

Technology Transfer Automated Retrieval System (TEKTRAN)

BACKGROUND: Folate deficiency decreases thymidylate synthesis from deoxyuridylate, which results in an imbalance of deoxyribonucleotide that may lead to excessive uracil misincorporation (UrMis) into DNA during replication and repair. OBJECTIVE: We evaluated the relation between UrMis in different ...

357

[Calcium antagonists: current and future applications based on new evidence. The mechanisms on lowering serum uric acid level by calcium channel blockers].  

PubMed

In hypertensive subjects, their serum uric acid levels tend to be higher because of decreasing urinary secretion or overproduction of uric acid. Among calcium channel blockers (CCBs) , long acting nifedipine and cilnidipine reveal serum uric acid lowering action. They decrease the production of uric acid precursor in skeletal muscles under anaerobic condition induced by hypertension or insulin resistance. Hyperuricemia is considered to be a risk factor of not only gout but also renal and cardiovascular diseases, thus, it is important to use CCBs without adverse effect on uric acid metabolisms. PMID:20048433

Mizuta, Einosuke; Hamada, Toshihiro; Igawa, Osamu; Shigemasa, Chiaki; Hisatome, Ichiro

2010-01-01

358

Vitamin B12 and pteroylglutamic acid studies in the domestic fowl  

E-print Network

? ration of vitamin B, p on the B-. P content of egg yolks........................... 5 Chapter 3. Factors affecting the in vitro conversion of folic acid (PGA) to the citrovorum factor (CF)............................ 29 Chapter 4. Effect of vitamin... of vitamin B^2 several workers (Doctor et al., '53; Drysdale et al., *51) have reported that the vitamin is implicated in utilization of pteroylglutamic acid (folic acid). Soon after the discovery of the citrovorum factor (OF, folinic acid...

Reid, Bobby Leroy

1955-01-01

359

The ascorbic acid content of stem rust susceptible and resistant wheat  

E-print Network

solutions containing one-tenth the normal amount of phosphorous was lower in folic acid, biotin, niacin and calcium pantothen? ate than plants grown in normal solutions of phosphorous. The control solution or normal solution contained 1.00 millimoles... of photo? synthesis and therefore influencing sugar production, which in turn# affects ascorbic acid production? Hotson (13) showed that P-arninobenzoic acid and folic acid are essential in metabolism and growth of stem rust* The work of McCoy et al...

Pilgrim, Arthur James

1955-01-01

360

GnRH antagonists  

Microsoft Academic Search

Ovarian stimulation is an important step in the success rate of in vitro fertilization (IVF) allowing multiple follicular growth, several oocytes and consequently more embryos. The combination of GnRH-antagonists (GnRH-ant) and gonadotrophins is now available for clinical use and represent a valid alternative to classical protocol with GnRH agonist. GnRH-antagonists induce a direct block of GnRH receptor with a rapid

Maria Elisabetta Coccia; Ciro Comparetto; Gian Luca Bracco; Gianfranco Scarselli

2004-01-01

361

Mesoporous Silica with Site-Isolated Amine and Phosphotungstic Acid Groups: A Solid Catalyst with Tunable Antagonistic Functions for One-Pot Tandem Reactions  

SciTech Connect

A bifunctional solid catalyst is prepared by combining acid and base functions on mesoporous silica supports. The co-existence of these functions is shown by a two-step reaction sequence in one pot. Excellent product yields, which cannot be obtained by separated acid and base functions in one pot, show the validity of our concept.

Shiju N. R.; Syed K.; Alberts A.; Brown D. and Rothenberg G.

2011-09-15

362

Synergistic and antagonistic effects between halide ions and carboxymethyl cellulose for the corrosion inhibition of mild steel in sulphuric acid solution  

Microsoft Academic Search

The corrosion and corrosion inhibition effect of carboxymethyl cellulose (CMC) for mild steel in sulphuric acid medium was\\u000a investigated using chemical (weight loss and hydrogen evolution) techniques at 30–60 °C. The effect of addition of halide\\u000a ions (Cl?, Br?, and I?) was also studied. It was found that CMC functions as an inhibitor for acid induced corrosion for mild steel. Inhibition

S. A. Umoren; M. M. Solomon; I. I. Udosoro; A. P. Udoh

2010-01-01

363

NR2B selective NMDA receptor antagonists.  

PubMed

NR2B antagonists have received considerable attention in recent years. In this class of excitatory amino acid receptor antagonists NR2B antagonists have shown efficacy in neuroprotection, anti-hyperalgesic and anti-Parkinson animal models. Several groups are involved in developing these compounds as therapeutic agents and evaluating newer therapeutic targets for these agents. Until recently benzylpiperidine and phenylpiperidine templates, which were based on the structures of Ifenprodil and Eliprodil, formed the basis of most SAR in this area. A few chemical leads in this class such as CP-101,606, Ro25,6981 and PD0196860 have been identified as possible development leads which have generated significant interest in this area. In addition to the efforts of Pfizer (Parke-Davis), Roche and E.Merck, several other industrial and academic research groups have continued to work in the NR2B area and recently Merck and Roche have reported new chemical leads as NR2B antagonists with significantly different biaryl templates. These new advances have raised hope, for potential success of the NR2B antagonists as new therapeutic agents, for the treatment of several pathophysiological indications. PMID:11945135

Nikam, Sham S; Meltzer, Leonard T

2002-01-01

364

Fish oil and 3-thia fatty acid have additive effects on lipid metabolism but antagonistic effects on oxidative damage when fed to rats for 50 weeks.  

PubMed

The 3-thia fatty acid tetradecylthioacetic acid (TTA) is a synthetic modified fatty acid, which, similar with dietary fish oil (FO), influences the regulation of lipid metabolism, the inflammatory response and redox status. This study was aimed to penetrate the difference in TTA's mode of action compared to FO in a long-term experiment (50 weeks of feeding). Male Wistar rats were fed a control, high-fat (25% w/v) diet or a high-fat diet supplemented with either TTA (0.375% w/v) or FO (10% w/v) or their combination. Plasma fatty acid composition, hepatic lipids and expression of relevant genes in the liver and biomarkers of oxidative damage to protein were assessed at the end point of the experiment. Both supplements given in combination demonstrated an additive effect on the decrease in plasma cholesterol levels. The FO diet alone led to removal of plasma cholesterol and a concurrent cholesterol accumulation in liver; however, with TTA cotreatment, the hepatic cholesterol level was significantly reduced. Dietary FO supplementation led to an increased oxidative damage, as seen by biomarkers of protein oxidation and lipoxidation. Tetradecylthioacetic acid administration reduced the levels of these biomarkers confirming its protective role against lipoxidation and protein oxidative damage. Our findings explore the lipid reducing effects of TTA and FO and demonstrate that these bioactive dietary compounds might act in a different manner. The experiment confirms the antioxidant capacity of TTA, showing an improvement in FO-induced oxidative stress. PMID:22221672

Vigerust, Natalya Filipchuk; Cacabelos, Daniel; Burri, Lena; Berge, Kjetil; Wergedahl, Hege; Christensen, Bjørn; Portero-Otin, Manuel; Viste, Asgaut; Pamplona, Reinald; Berge, Rolf Kristian; Bjørndal, Bodil

2012-11-01

365

Identification of amino acids in the nicotinic acetylcholine receptor agonist binding site and ion channel photolabeled by 4-[(3-trifluoromethyl)-3H-diazirin-3-yl]benzoylcholine, a novel photoaffinity antagonist.  

PubMed

[(3)H]4-[(3-trifluoromethyl)-3H-diazirin-3-yl]benzoylcholine (TDBzcholine) was synthesized and used as a photoaffinity probe to map the orientation of an aromatic choline ester within the agonist binding sites of the Torpedo nicotinic acetylcholine receptor (nAChR). TDBzcholine acts as a nAChR competitive antagonist that binds at equilibrium with equal affinity to both agonist sites (K(D) approximately 10 microM). Upon UV irradiation (350 nm), nAChR-rich membranes equilibrated with [(3)H]TDBzcholine incorporate (3)H into the alpha, gamma, and delta subunits in an agonist-inhibitable manner. The specific residues labeled by [(3)H]TDBzcholine were determined by N-terminal sequence analysis of subunit fragments produced by enzymatic cleavage and purified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and/or reversed-phase high-performance liquid chromatography. For the alpha subunit, [(3)H]TDBzcholine photoincorporated into alphaCys-192, alphaCys-193, and alphaPro-194. For the gamma and delta subunits, [(3)H]TDBzcholine incorporated into homologous leucine residues, gammaLeu-109 and deltaLeu-111. The photolabeling of these amino acids suggests that when the antagonist TDBzcholine occupies the agonist binding sites, the Cys-192-193 disulfide and Pro-194 from the alpha subunit Segment C are oriented toward the agonist site and are in proximity to gammaLeu-109/deltaLeu-111 in Segment E, a conclusion consistent with the structure of the binding site in the molluscan acetylcholine binding protein, a soluble protein that is homologous to the nAChR extracellular domain. PMID:12525154

Chiara, David C; Trinidad, Jonathan C; Wang, Dong; Ziebell, Michael R; Sullivan, Deirdre; Cohen, Jonathan B

2003-01-21

366

Opioid Antagonist Impedes Exposure.  

ERIC Educational Resources Information Center

Thirty spider-phobic adults underwent exposure to 17 phobic-related, graded performance tests. Fifteen subjects were assigned to naltrexone, an opioid antagonist, and 15 were assigned to placebo. Naltrexone had a significant effect on exposure, with naltrexone subjects taking significantly longer to complete first 10 steps of exposure and with…

Merluzzi, Thomas V.; And Others

1991-01-01

367

Characterization of a novel and potent collagen antagonist, caffeic acid phenethyl ester, in human platelets: In vitro and in vivo studies  

Microsoft Academic Search

Objective: Caffeic acid phenethyl ester (CAPE), which is derived from the propolis of honeybee hives, has been demonstrated to possess multiple pharmacological activities. In the present study, CAPE (6-25 ?M) specifically inhibited collagen-induced platelet aggregation and the ATP release reaction in platelet suspensions. Methods: Platelet aggregation, flow cytometric analysis, immunoblotting, and electron spin resonance (ESR) were used to assess the

George Hsiao; Jie J. Lee; Kuang H. Lin; Chia H. Shen; Tsorng H. Fong; Duen S. Chou; Joen R. Sheu

2007-01-01

368

Xanthines as Adenosine Receptor Antagonists  

PubMed Central

The natural plant alkaloids caffeine and theophylline were the first adenosine receptor (AR) antagonists described in the literature. They exhibit micromolar affinities and are non-selective. A large number of derivatives and analogs have subsequently been synthesized and evaluated as AR antagonists. Very potent antagonists have thus been developed with selectivity for each of the four AR subtypes. PMID:20859796

Jacobson, Kenneth A.

2013-01-01

369

Antagonist Treatment of Opioid Withdrawal  

Microsoft Academic Search

Although antagonist drugs are receiving increasing attention in the treatment of opioid withdrawal, the mechanisms of interaction of opiate agonists and antagonists remain largely to be investigated. We focused on the effects of very low quantities of opiate antagonists, for their potential utility in detoxification. Upon reviewing the evidence on the administration of small doses of naloxone and naltrexone in

Paolo Mannelli; Edward Gottheil; Elisabeth J. Van Bockstaele

2006-01-01

370

Solving time-dependent CYP3A4 inhibition for a series of indole-phenylacetic acid dual antagonists of the PGD(2) receptors CRTH2 and DP.  

PubMed

Based on their structural similarity to previously described compound AMG 009, indole-phenyl acetic acids were proposed to be potent dual inhibitors of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2 or DP2) and prostanoid D receptor (DP or DP1). This series was equipotent to AMG 009 in binding assays against both receptors but exhibited decreased serum shift. We discovered early in the optimization of these indole-phenylacetic acid compounds that they demonstrated CYP3A4 time-dependent inhibition (TDI). Hypothesizing that the source of TDI was the indole core we modified the 1,2,3-substitution to eventually afford a highly potent modulator of CRTH2 and DP which did not exhibit TDI. PMID:24825301

Johnson, Michael G; Liu, Jim Jiwen; Li, An-Rong; van Lengerich, Bettina; Wang, Sophie; Medina, Julio C; Collins, Tassie L; Danao, Jay; Seitz, Lisa; Willee, Angela; D'Souza, Warren; Budelsky, Alison L; Fan, Peter W; Wong, Simon G W

2014-07-01

371

Synergistic and antagonistic effect of lactic acid bacteria on tyramine production by food-borne pathogenic bacteria in tyrosine decarboxylase broth  

Microsoft Academic Search

The effect of lactic acid bacteria (LAB) strains on tyramine (TYR) and also other biogenic amines (BA) production by eight common food-borne pathogen (FBP) in tyrosine decarboxylase broth (TDB) was investigated by using a rapid HPLC method. Significant differences were observed among the FBP strains in ammonia (AMN) and BA production apart from tryptamine, histamine (HIS) and spermine formation (p<0.05).

Esmeray Kuley; Fatih Özogul

2011-01-01

372

Anticonvulsant activity of 4-urea-5,7-dichlorokynurenic acid derivatives that are antagonists at the NMDA-associated glycine binding site  

Microsoft Academic Search

Twelve 4-urea-5,7-dichlorokynurenic acid derivatives were synthesized by reacting the 4-tosylimino derivative of 5,7-dichlorokynurenate\\u000a methyl ester first with triphosgene and then with a secondary amine. Compounds were screened in mice for anticonvulsant activity\\u000a using maximal electroshock (MES), subcutaneous pentylenetetrazole (Met), and threshold tonic extension (TTE) tests. A rotorod\\u000a test was used to determine neurotoxicity. Seven of the derivatives had anticonvulsant activity

Alfred C. Nichols; K. Lemone Yielding

1998-01-01

373

Effect of BN 52021, a specific antagonist of platelet activating factor (PAF-acether), on calcium movements and phosphatidic acid production induced by PAF-acether in human platelets  

SciTech Connect

/sup 32/P-labelled human platelets loaded with quin 2 and pretreated with aspirin were stimulated with 1-100 nM platelet activating factor (PAF-acether or 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine) in a medium containing the ADP-scavenging system creatine phosphate/creatine phosphokinase. Under these conditions, PAF-acether evoked a characteristic fluorescence change allowing to quantify elevations in cytoplasmic free Ca/sup 2 +/ from internal stores (Ca/sup 2 +/ mobilization) or from external medium (Ca/sup 2 +/ influx), as well as an increased production of phosphatidic acid, reflecting phospholipase C activation. These effects, which can be attributed to PAF-acether only and not to released products such as ADP or thromboxane A2, were strongly inhibited in a dose-dependent manner by BN 52021, a specific antagonist of PAF-acether isolated from Ginkgo biloba. As the drug remained inactive against the same effects elicited by thrombin, it is concluded that BN 52021 does not interfere directly with the mechanism of transmembrane signalling involving inositol-phospholipids or (and) some putative receptor-operated channels, but rather acts on the binding of PAF-acether to its presumed membrane receptor.

Simon, M.F.; Chap, H.; Braquet, P.; Douste-Blazy, L.

1987-02-15

374

Antagonistic properties of a natural product - Bicuculline with the gamma-aminobutyric acid receptor: Studied through electrostatic potential mapping, electronic and vibrational spectra using ab initio and density functional theory  

NASA Astrophysics Data System (ADS)

(+)-Bicuculline (hereinafter referred to as bicuculline), a phthalide isoquinoline alkaloid is of current interest as an antagonist of gamma-aminobutyric acid (GABA). Its inhibitor properties have been studied through molecular electrostatic potential (MEP) mapping of this molecule and GABA receptor. The hot site on the potential surface of bicuculline, which is also isosteric with GABA receptor, has been used to interpret the inhibitor property. A systematic quantum chemical study of the possible conformations, their relative stabilities, FT-Raman, FT-IR and UV-vis spectroscopic analysis of bicuculline has been reported. The optimized geometries, wavenumber and intensity of the vibrational bands of all the conformers of bicuculline have been calculated using ab initio Hartree-Fock (HF) and density functional theory (DFT) employing B3LYP functional and 6-311G(d,p) basis set. Mulliken atomic charges, HOMO-LUMO gap ? E, ionization potential, dipole moments and total energy have also been obtained for the optimized geometries of both the molecules. TD-DFT method is used to calculate the electronic absorption parameters in gas phase as well as in solvent environment using integral equation formalism-polarizable continuum model (IEF-PCM) employing 6-31G basis set and the results thus obtained are compared with the UV absorption spectra. The combination of experimental and calculated results provides an insight into the structural and vibrational spectroscopic properties of bicuculline.

Srivastava, Anubha; Tandon, Poonam; Jain, Sudha; Asthana, B. P.

2011-12-01

375

High-performance liquid chromatography-tandem mass spectrometry method for the determination of perampanel, a novel ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist in human plasma.  

PubMed

Perampanel (Fycompa(®)) is a novel ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist registered for the adjunctive treatment of patients (?12 years) with refractory partial onset seizures. In order to support clinical trials, as well as therapeutic drug monitoring, a sensitive bioanalytical method for the determination of perampanel concentrations in human plasma was established and validated using liquid chromatography with tandem mass spectrometry. Perampanel and an internal standard were extracted from human plasma (100?L) by liquid extraction using methyl t-butyl ether, then evaporated and reconstituted. The chromatographic separation was conducted on a C8 column with isocratic elution at a flow rate of 0.2mL/min. The established method showed linearity in the range 0.25-200ng/mL with correlation coefficients of >0.99 that could be extended 10-fold as validated by dilution integrity analyses. No significant endogenous peaks were detected in the elution of analytes in blank human plasma and no significant matrix effect was observed. The intra- and inter-batch reproducibility analyses demonstrated accuracy and precision within the acceptance criteria. To check the impact of anti-epileptic drugs on the perampanel assay, accuracy, precision, and specificity were assessed in the presence of 14 anti-epileptic drugs. No anti-epileptic drugs at clinically relevant levels showed a significant impact on the perampanel assay. PMID:25569285

Mano, Yuji; Takenaka, Osamu; Kusano, Kazutomi

2015-03-25

376

A comparative assessment of ?-lipoic acid N-phenylamides as non-steroidal androgen receptor antagonists both on and off gold nanoparticles.  

PubMed

A group of ?-lipoic acid N-phenylamides were synthesized employing a variety of amide coupling protocols utilizing electron deficient anilines. These compounds were then assessed for their ability to block androgen-stimulated proliferation of a human prostate cancer cell line, LNCaP. These structurally simple compounds displayed anti-proliferative activities at, typically, 5-20 ?M concentrations and were comparable to a commonly used anti-androgen Bicalutamide®. The inclusion of a disulfide (RS-SR) moiety, serving as an anchor to several metal nanoparticle systems (Au, Ag, Fe(2)O(3), etc.), does not impede any biological activity. Conjugation of these compounds to a gold nanoparticle surface resulted in a high degree of cellular toxicity, attributed to the absence of a biocompatible group such as PEG within the organic scaffold. PMID:22196975

Henderson, Luke C; Altimari, Jarrad M; Dyson, Gail; Servinis, Linden; Niranjan, Birunthi; Risbridger, Gail P

2012-02-01

377

Amino acid sequence and molecular modelling of glycoprotein IIb-IIIa and fibronectin receptor iso-antagonists from Trimeresurus elegans venom.  

PubMed

Low-molecular-mass Arg-Gly-Asp (RGD)-containing polypeptides were isolated from the venom of Trimeresurus elegans by a simple two-step procedure consisting of membrane filtration and reverse-phase HPLC. A combination of electrospray MS, fast-atom bombardment MS and Edman degradation allowed us to ascertain the presence in the venom of different isoforms and to determine their primary structures. The amino acid sequences resembled the structure of elegantin, the only disintegrin previously reported from the T. elegans venom [Williams, Rucinski, Holt and Niewiarowski (1990) Biochim. Biophys, Acta 1039, 81-89]. MS analyses indicated the occurrence of differential proteolytic processing at both the N-terminus and the C-termins of the polypeptide chains. The amino acid sequence alignment of the elegantin isoforms with known components of the disintegrin family demonstrated the complete conservation of the 12 cysteine residues involved in disulphide bridges. Molecular modelling of elegantins predicted an overall folding of these molecules quite similar to that reported for the kistrin solution structure. The newly identified polypeptide isoforms strongly inhibited ADP-induced aggregation in both human and canine platelet-rich plasma but showed a different species-dependent specificity. These molecules were also able to inhibit B16-BL6 murine melanoma cell adhesion to immobilized fibronectin. The comparison of the structures and biological activities of elegantin isoforms and kistrin allowed us to highlight some structural features that, in addition to the RGD locus might be involved in the interaction of these snake-venom polypeptides with the integrin receptors on the platelet and cell surface. PMID:8920980

Scaloni, A; Di Martino, E; Miraglia, N; Pelagalli, A; Della Morte, R; Staiano, N; Pucci, P

1996-11-01

378

Prostaglandin EP4 antagonists.  

PubMed

Prostaglandin antagonists, with their pharmacological effects, are well-known drugs capable of treating widely diffused illnesses, including pain and inflammation disorders. In recent years, a major research focus has been devoted to the identification of agents able to selectively antagonize each receptor with which prostaglandins interact. This review attempts to give a broad overview of molecules capable of selectively blocking the prostaglandin PGE2 EP4 receptor. Further therapeutic applications and uses have also been disccussed, including the first drug candidate to have reached clinical trials within the last few years. PMID:24237064

Borriello, Manuela; Stasi, Luigi Piero

2013-05-01

379

The development of cannabinoid antagonists.  

PubMed

The discovery of two distinct cannabinoid receptors (CB1 and CB2) in the early 1990's has revived the research on cannabinoid antagonists. While the search for antagonists based on the structure of agonists (classical cannabinoids or aminoalkylindoles) appeared rather disappointing, the first potent cannabinoid antagonists were developed in a new chemical series: the diarylpyrazoles. Since its discovery in 1994, the selective CB1 antagonist SR 141716 has became a major pharmacological tool to elucidate the physiological role of the CB1 cannabinoid receptor and its endogenous ligand. The selective CB2 antagonist SR 144528 is expected to play the same role for the CB2 receptors, while the recent development of cannabinoid antagonists belonging to other chemical series illustrates the interest of these compounds which are now considered as interesting therapeutic targets by many pharmaceutical companies. PMID:10469889

Barth, F; Rinaldi-Carmona, M

1999-08-01

380

SDZ 205-557, a selective, surmountable antagonist for 5HT 4 receptors in the isolated guinea pig ileum  

Microsoft Academic Search

A selective antagonist for the recently characterized 5-HT4-receptor is lacking. The only surmountable antagonist available, ICS 205-930, is a weak antagonist and is far more potent at 5-HT3-than at 5-HT4 receptors. In this paper, SDZ 205-557 (2-methoxy-4-amino-5-chloro-benzoic acid 2-(diethylamino) ethyl ester) is characterized as the first potent, selective and surmountable antagonist at 5-HT4 receptors in the isolated guinea pig ileum.

Karl-Heinz Buchheit; Rainer Gamse; Hans-Jtirgen Pfannkuche

1992-01-01

381

n -3 Fatty acids plus oleic acid and vitamin supplemented milk consumption reduces total and LDL cholesterol, homocysteine and levels of endothelial adhesion molecules in healthy humans  

Microsoft Academic Search

Background and aims: Numerous studies suggest n -3 polyunsaturated fatty acids (n -3 PUFA) and oleic acid intake have beneficial effects on health including risk reduction of coronary heart disease. The purpose of this study was to evaluate the effect of a commercially available skimmed milk supplemented with n -3 PUFA, oleic acid, and vitamins E, B6, and folic acid

L. BARÓ; J. FONOLLÁ; J. L. PEÑA; A. MARTÍNEZ-FÉREZ; A. LUCENA; J. JIMÉNEZ; J. J. BOZA; E. LÓPEZ-HUERTAS

2003-01-01

382

Maternal micronutrients, omega-3 fatty acids, and placental PPAR? expression.  

PubMed

An altered one-carbon cycle is known to influence placental and fetal development. We hypothesize that deficiency of maternal micronutrients such as folic acid and vitamin B12 will lead to increased oxidative stress, reduced long-chain polyunsaturated fatty acids, and altered expression of peroxisome proliferator activated receptor (PPAR?) in the placenta, and omega-3 fatty acid supplementation to these diets will increase the expression of PPAR?. Female rats were divided into 5 groups: control, folic acid deficient, vitamin B12 deficient, folic acid deficient + omega-3 fatty acid supplemented, and vitamin B12 deficient + omega-3 fatty acid supplemented. Dams were dissected on gestational day 20. Maternal micronutrient deficiency leads to lower (p < 0.05) levels of placental docosahexaenoic acid, arachidonic acid, PPAR? expression and higher (p < 0.05) levels of plasma malonidialdehyde, placental IL-6, and TNF-?. Omega-3 fatty acid supplementation to a vitamin B12 deficient diet normalized the expression of PPAR? and lowered the levels of placental TNF-?. In the case of supplementation to a folic acid deficient diet it lowered the levels of malonidialdehyde and placental IL-6 and TNF-?. This study has implications for fetal growth as oxidative stress, inflammation, and PPAR? are known to play a key role in the placental development. PMID:24749811

Meher, Akshaya P; Joshi, Asmita A; Joshi, Sadhana R

2014-07-01

383

Identification of 2-(2-(1-naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid (setipiprant/ACT-129968), a potent, selective, and orally bioavailable chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonist.  

PubMed

Herein we describe the discovery of the novel CRTh2 antagonist 2-(2-(1-naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid 28 (setipiprant/ACT-129968), a clinical development candidate for the treatment of asthma and seasonal allergic rhinitis. A lead optimization program was started based on the discovery of the recently disclosed CRTh2 antagonist 2-(2-benzoyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid 5. An already favorable and druglike profile could be assessed for lead compound 5. Therefore, the lead optimization program mainly focused on the improvement in potency and oral bioavailability. Data of newly synthesized analogs were collected from in vitro pharmacological, physicochemical, in vitro ADME, and in vivo pharmacokinetic studies in the rat and the dog. The data were then analyzed using a traffic light selection tool as a visualization device in order to evaluate and prioritize candidates displaying a balanced overall profile. This data-driven process and the excellent results of the PK study in the rat (F = 44%) and the dog (F = 55%) facilitated the identification of 28 as a potent (IC50 = 6 nM), selective, and orally available CRTh2 antagonist. PMID:23721423

Fretz, Heinz; Valdenaire, Anja; Pothier, Julien; Hilpert, Kurt; Gnerre, Carmela; Peter, Oliver; Leroy, Xavier; Riederer, Markus A

2013-06-27

384

Cardiovascular effects of the new generation calcium antagonist 3-pyridine carboxylic acid 5-[(cyclopropylamino)carbonyl]-1,4-dihydro-2,6-dimethyl-4-(2-nitropheny l) octyl ester.  

PubMed

The cardiovascular effects of 3-pyridine carboxylic acid 5-[(cyclopropylamino)carbonyl]-1,4-dihydro-2,6-dimethyl-4-(2-nitro phenyl) oxtyl ester (NP-252, CAS 132031-81-3) were examined in anesthetized closed- or open-chest dogs and Langendorff perfused rabbit hearts, and compared with those of nifedipine (NF) and nicardipine (NC). In anesthetized closed- and open-chest dogs, NP-252 (i.v.) selectively increased vertebral and coronary blood flow with a fall in mean blood pressure (MBP). These effects were nearly equipotent with those of NF and NC, but more durable. A similar effect was obtained by intraduodenal administration of NP-252. Also, NP-252 (i.v.) decreased MBP, total peripheral resistance (TPR), left ventricular pressure and dLVP/dtmax while cardiac output (CO) and stroke volume (SV) increased without apparent changes in heart rate and myocardial contractility index. Decreases in MBP and TPR by NP-252 were equipotent with NF and NC, whereas increases in CO and SV were more potent than those of the two drugs. These actions of NP-252 were longer than those of the reference agents. Further, in perfused rabbit hearts, NO-252 increased coronary perfusion flow (CPF), accompanying a slight negative inotropy. Its effect in CPF was equipotent with NF and 2 times less than that of NC, however the duration was much longer than those of the reference drugs. On the other hand, the negative inotropic effect of NP-252 was less than NF, but greater than that of NC. In the preparations controlled by pacing, NP-252 and NF lengthened atrio-His bundle conduction time, without affecting His bundle-ventricular conduction time. Lengthening effect of NP-252 was about 4 times less than that of NF. These results suggest that NP-252 acts more selectively on vascular smooth muscle than cardiac muscle, and has almost equipotent but markedly longer vasodilating actions as compared to NF and NC. It may be expected that NP-252 is a new generation of tissue specific and long acting Ca2+ antagonist. PMID:1530674

Hojo, M; Teramoto, N; Hata, H; Katayama, O; Tatsumi, H; Shibata, S

1992-05-01

385

Wnt pathway antagonists and angiogenesis  

Microsoft Academic Search

Dysregulation of the Wnt pathway has been extensively studied in multiple diseases, including some angiogenic disorders. Wnt\\u000a signaling activation is a major stimulator in pathological angiogenesis and thus, Wnt antagonists are believed to have therapeutic\\u000a potential for neovascular disorders. Actually, some Wnt antagonists have been identified directly from the anti-angiogenic\\u000a factor family. This review summarizes the recent progress toward understanding

Bin Zhang; Jian-xing Ma

2010-01-01

386

Effects of fibrinogen receptor antagonist GR144053F and aurintricarboxylic acid on platelet activation and degranulation 1 1 Abbreviations: ACD, citric acid\\/trisodium citrate\\/glucose (recipe A), blood anticoagulant; ATA, aurintricarboxylic acid; CT CADP, closure (occlusion) time determined with the use of collagen\\/ADP cassettes in PFA100; GPIb-IX-V, a complex of glycoproteins Ib, IX, and V, a vWF receptor; GPIIb-IIIa, a complex of glycoproteins IIb and IIIa, a fibrinogen receptor; ic 50, the concentration of an inhibitor, at which 50% of the maximal estimated inhibition occurred; the extent of maximal inhibition was calculated based on the mathematical resolving of the equation describing the inhibition of platelet aggregation; PE, R-phycoerythrin; PFA100™, platelet function analyzer; PRP, platelet-rich plasma; RGD, Arg-Gly-Asp; PBS, phosphate-buffered saline; TRAP, thrombin receptor activating peptide, SFLLRNPNDKYEPF; and vWF, von Willebrand factor  

Microsoft Academic Search

Activated blood platelets play crucial role in restenosis due to their fundamental significance in thrombus formation. Therefore, platelets are attractive targets for the inhibition with a variety of antagonists. In this study, we present direct evidence that GR144053F [non-peptide antagonist of glycoprotein IIb-IIIa complex (GPIIb-IIIa)] inhibits activation and degranulation of human platelets, and opposes the action of aurintricarboxylic acid (ATA),

Marcin Rozalski; Magdalena Boncler; Jacek Golanski; Cezary Watala

2001-01-01

387

Selective antagonists of benzodiazepines  

Microsoft Academic Search

Benzodiazepines produce most, if not all, of their numerous effects on the central nervous system (CNS) primarily by increasing the function of those chemical synapses that use gamma-amino butyric acid (GABA) as transmitter1,2. This specific enhancing effect on GABAergic synaptic inhibition is initiated by the interaction of benzodiazepines with membrane proteins of certain central neurones, to which drugs of this

W. Hunkeler; H. Möhler; L. Pieri; P. Polc; E. P. Bonetti; R. Cumin; R. Schaffner; W. Haefely

1981-01-01

388

Antagonists for acute oral cadmium chloride intoxication  

SciTech Connect

An examination has been carried out on the relative efficacy of a number of chelating agents when acting as antagonists for oral cadmium chloride intoxication in mice. The compounds were administered orally after the oral administration of cadmium chloride at 1 mmol/kg. Of the compounds examined, several were useful in terms of enhancing survival, but by far the most effective in both enhancing survival and leaving minimal residual levels of cadmium in the liver and the kidney, was meso-2,3-dimercaptosuccinic acid (DMSA). Several polyaminocarboxylic acids also enhanced survival. The most effective of these in reducing liver and kidney levels of cadmium were diethylenetriaminepentaacetic acid (DTPA), trans-1,2-diaminocyclohexane-N,N,N'N'-tetraacetic acid (CDTA), and triethylenetetraminehexaacetic acid (TTHA). D-Penicillamine (DPA) was found to promote survival but also led to kidney cadmium levels higher than those found in the controls. Sodium 2,3-dimercaptopropane-1-sulfonate (DMPS) was as effective in promoting survival as DMSA but left levels of cadmium in the kidney and liver that were approximately four times greater than those found with DMSA.

Basinger, M.A.; Jones, M.M.; Holscher, M.A.; Vaughn, W.K.

1988-01-01

389

A study of the effect of pantothenic acid deficiency on the reproductive organs of the male albino rat  

E-print Network

". istochemical reactions (Deans, I)cKibbin, 'l]C&) . Experiments 'by (Wright and Welch, '44) denio:ist "Ptcd thiit a, relutioii- ship exists between i'olic acid. , biotin, and paiitothenic ac'd. Thc 3 &I&iiiio 1 o' b! etii& a&&d folic acid I o tl c: &' ' 't... arne uc40 1830 gO 150 30 30 c ~ c. IIater Soluble Vitamin. Iiixture (Amounts Siven per 1000 c. c. of' distilled. water) 'Znicmine hydrochloride Niacin Xnositol Choline chlorld. e Para amino cenozoic acid. Folic acid Pyridoxine Biotin...

Lorenzen, Gerald Andrew

1958-01-01

390

Two Cases of H2-Receptor Antagonist Hypersensitivity and Cross-Reactivity  

PubMed Central

H2-receptor antagonists, such as cimetidine, ranitidine and famotidine, are some of the most commonly prescribed medications for gastric acid-related disorders. These compounds are generally well-tolerated and anaphylactic reactions to them are rare. Here, we report two cases of H2-receptor antagonist-induced anaphylactic reactions: the first presented with sudden dyspnea, sneezing, urticaria, and swelling of the eyelids after ranitidine intake. The second presented with sudden severe urticaria, facial swelling, chest discomfort, dizziness, and hypotension. Possible cross-reactivity with other H2-receptor antagonists was assessed by oral challenge and skin tests. To date, only a few reports addressing cross-reactivity among H2-receptor antagonists have been published. We review the literature and summarize the data available on drug cross-reactivity in H2-receptor antagonist hypersensitivity. PMID:21461253

Song, Woo-Jung; Kim, Min-Hye; Lee, Sang-Min; Kwon, Yong-Eun; Kim, Sae-Hoon; Cho, Sang-Heon; Min, Kyung-Up; Kim, You-Young

2011-01-01

391

Non-NMDA receptor antagonist-induced drinking in rat  

NASA Technical Reports Server (NTRS)

Glutamate has been implicated in the central control of mechanisms that maintain body fluid homeostasis. The present studies demonstrate that intracerebroventricular (i.c.v.) injections of the non-N-methyl-d-aspartate (NMDA) receptor antagonists 6, 7-dinitroquinoxaline-2,3-dione (DNQX) and 6-cyano-7-nitroquinoxaline-2,3 dione (CNQX) induce drinking in rats. The dipsogenic effect of i.c.v. DNQX was antagonized by the non-NMDA receptor agonist alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). The water intake induced by DNQX was also blocked by pretreatment with a NMDA receptor antagonist, MK-801, but not by angiotensin type 1 (AT1) or acetylcholine muscarinic receptor antagonists (losartan and atropine). The results indicate that non-NMDA receptors may exert a tonic inhibitory effect within brain circuits that control dipsogenic activity and that functional integrity of NMDA receptors may be required for the non-NMDA receptor antagonists to induce water intake. Copyright 1998 Published by Elsevier Science B.V.

Xu, Z.; Johnson, A. K.

1998-01-01

392

TRPV4 agonists and antagonists.  

PubMed

TRPV4 belongs to the TRPV subfamily of Transient Receptor Potential (TRP) ion channels. This year marks the 10 year anniversary of the discovery of this polymodal ion channel which is activated by a variety of stimuli including warm temperatures, hypotonicity and endogenous lipids. Coupled with a widespread tissue distribution, this activation profile has resulted in a large number of disparate physiological functions for TRPV4. These range from temperature monitoring in skin keratinocytes to osmolarity sensing in kidneys, sheer stress detection in blood vessels and osteoclast differentiation control in bone. As knowledge of its physiological roles has expanded, interest in targeting TRPV4 modulation for therapeutic purposes has arisen and is now focused on several areas. First, as with related TRP channels TRPV1, TRPV3, TRPM8 and TRPA1, TRPV4 antagonism is being considered for inflammatory and neuropathic pain treatment. Recent work conducted using KO mice and agonists 4?PDD and GSK1016790A suggests bladder dysfunctions may also be targeted. Additionally, ventilator-induced lung injury has emerged as another potential indication for TRPV4 antagonists. Herein we review the known small molecule modulators of TRPV4 and relate progress made in identifying potent, selective and bioavailable agonists and antagonists to interrogate this ion channel in vivo. PMID:21671873

Vincent, Fabien; Duncton, Matthew A J

2011-01-01

393

Dietary Intake of Natural Sources of Docosahexaenoic Acid and Folate in Pregnant Women of Three European Cohorts  

Microsoft Academic Search

Background: Folic acid plays a fundamental role in cell division and differentiation. Docosahexaenoic acid (DHA) has been associated with infantile neurological and cognitive development. Thus, optimal intrauterine development and growth requires adequate supply of these nutrients during pregnancy. Methods: Healthy pregnant women, aged 18–41 years, were recruited in Granada (Spain; n = 62), Munich (Germany; n = 97) and Pécs

C. Franke; S. Verwied-Jorky; C. Campoy; M. Trak-Fellermeier; T. Decsi; V. Dolz; B. Koletzko

2008-01-01

394

A new alcohol antagonist: Phaclofen  

SciTech Connect

The ability of the GABA{sub B} receptor antagonist, phaclofen to alter behavioral effects of ethanol was evaluated by loss of righting reflex (sleep time), motor incoordination (bar holding), spontaneous locomotion (open field activity) and hypothermia. Pretreatment with phaclofen significantly decreased the effects of ethanol on motor incoordination, locomotor activity and hypothermia. However, phaclofen had no effect on either pentobarbital- or diazepam-induced motor incoordination. Phaclofen slightly increased the ED{sub 50} for loss of the righting reflex but did not alter either the duration of reflex loss produced by ethanol or blood ethanol levels at awakening. Our results suggest phaclofen is rapidly inactivated resulting in difficulty in observing antagonism of long duration ethanol effects. These findings suggest that the GABA{sub B} system may play a role in mediating several important actions of ethanol.

Allan, A.M. (Washington Univ. School of Medicine, Saint Louis, MO (USA)); Harris, R.A. (Univ. of Colorado School of Medicine, Denver (USA))

1989-01-01

395

Peptide antagonist of the androgen receptor.  

PubMed

Androgen receptor (AR) is a steroid hormone receptor that is activated by endogenous androgens, mainly testosterone and 5alpha-dihydrotestosterone (5alpha-DHT). AR is also an important drug target, and AR antagonists (antiandrogens) have been widely used for prostate cancer therapy. Antiandrogens currently available on the market are all small molecules that antagonize AR function via binding to the ligand binding domain (LBD). AR peptide antagonist has been proposed as a 'mechanism-based' approach to directly block AR function by interrupting AR-protein interactions from the surface of the receptor. Without targeting the rigid ligand binding pocket within LBD, peptide antagonists allow more flexibility in structure design, and are likely to provide more efficient and complete blockade of AR function as compared to small molecule antagonists. AR interacts with a variety of proteins, and the interaction may be mediated by different functional domains of the receptor. Although varieties of AR-protein interfaces might serve as the target for peptide antagonist, majority of ongoing research is still focusing on peptides that target the LBD, which is mainly due to the abundance of structural information revealed by crystal structures. This review gives an overview of the current research attempts to develop AR peptide antagonists, particularly peptide antagonists that target the LBD and N-terminal domain (NTD). The challenges and opportunities for future discovery and development of peptide antagonists are discussed as well. PMID:20030610

Gao, Wenqing

2010-01-01

396

Configurationally Restricted Bismacrocyclic CXCR4 Receptor Antagonists  

E-print Network

Configurationally Restricted Bismacrocyclic CXCR4 Receptor Antagonists Gina C. Valks, Graeme Mc configurationally restricted analogue of bismacrocyclic cyclam-type CXCR4 chemokine receptor antagonists has been,4,8,11-tetraazacyclotetradecane)), Figure 1c, is a drug that interacts with a cell surface protein (CXCR4) via hydrogen bonding

Hubin, Tim

397

Chemokine receptor antagonists: overcoming developmental hurdles  

Microsoft Academic Search

Chemokine receptors have a key role in the pathogenesis of autoimmune diseases, inflammation and viral infection. However, with the exception of selective CCR5 antagonists for HIV, the promise of obtaining new therapeutics related to chemokine receptors has not yet been realized. This article highlights some of the recent failures in the clinical trials of chemokine receptor antagonists and explores possible

Richard Horuk

2008-01-01

398

PAR-1 antagonists: current state of evidence.  

PubMed

Vorapaxar (SCH 530348) and atopaxar (E5555) are oral protease-activated receptor-1 (PAR-1) antagonists with high bioavailability. They inhibits thrombin induced platelet aggregation by competitively inhibiting PAR-1. We systematically evaluated the evidence for the efficacy and safety of all PAR-1 antagonists as well as for the individual drugs vorapaxar and atopaxar in different databases-PubMed, EMBASE, Scopus, and Cochrane register of Controlled Clinical Trials (CENTRAL).We selected randomized controlled trials of PAR-1 antagonists that reported on cardiovascular mortality as a clinical outcome. The random-effects Mantel-Haenszel model was used to evaluate the effect of PAR-1 antagonists on cardiovascular mortality. Seven trials were selected (N = 42,355) for analysis. PAR-1 antagonists as a class, as well as individually, were associated with a non-significant numerically lower risk of cardiovascular mortality than that seen with agents used in the control group; RR, 0.93; 95% CI, 0.83-1.04; P = 0.20). No heterogeneity was noted. However, PAR-1 antagonists also appeared to increase the risk of bleeding significantly. PAR-1 antagonists appear to be associated with some reduction in the risk of cardiovascular mortality; however the significantly higher bleeding risk noted with PAR-1 antagonists appear to mandate a very careful selection of patients that may benefit without a substantially increased risk of bleeds. PMID:22644721

Chatterjee, Saurav; Sharma, Abhishek; Mukherjee, Debabrata

2013-01-01

399

Detecting sexual conflict and sexually antagonistic coevolution  

E-print Network

Detecting sexual conflict and sexually antagonistic coevolution Locke Rowe1,2,* and Troy Day3,4 1 by providing an operational definition of sexual conflict that applies to both inter- and intralocus conflict approaches for detecting interlocus sexual conflict and resultant sexually antagonistic coevolution. We

Day, Troy

400

5-Methyltetrahydrofolate, the active form of folic acid, restores endothelial function in familial hypercholesterolemia  

Microsoft Academic Search

Background—Impaired nitric oxide (NO) activity is an early event in the pathogenesis of cardiovascular disease, resulting from either reduced NO formation or increased NO degradation. Administration of tetrahydrobiopterin (BH4), an essential cofactor for NO production, could restore NO activity in familial hypercholesterolemia (FH). Because folates have been suggested to stimulate endogenous BH4 regeneration, we hypothesized that administration of 5-methyltetrahydrofolate (5-MTHF,

Marianne C. Verhaar; Robert M. F. Wever; John J. P. Kastelein; Thea van Dam; Hein A. Koomans; Ton J. Rabelink

1998-01-01