Background: Oral clefts are one of the most common birth defects with significant medical, psychosocial, and economic ramifications. Oral clefts have a complex etiology with genetic and environmental risk factors. There are suggestive results for decreased risks of cleft occurrence and recurrence with folic acid supplements taken at preconception and during pregnancy with a stronger evidence for higher than lower doses in preventing recurrence. Yet previous studies have suffered from considerable design limitations particularly non-randomization into treatment. There is also well-documented effectiveness for folic acid in preventing neural tube defect occurrence at 0.4 mg and recurrence with 4 mg. Given the substantial burden of clefting on the individual and the family and the supportive data for the effectiveness of folic acid supplementation as well as its low cost, a randomized clinical trial of the effectiveness of high versus low dose folic acid for prevention of cleft recurrence is warranted. Methods/design: This study will assess the effect of 4 mg and 0.4 mg doses of folic acid, taken on a daily basis during preconception and up to 3 months of pregnancy by women who are at risk of having a child with nonsyndromic cleft lip with/without palate (NSCL/P), on the recurrence of NSCL/P. The total sample will include about 6,000 women (that either have NSCL/P or that have at least one child with NSCL/P) randomly assigned to the 4 mg and the 0.4 mg folic acid study groups. The study will also compare the recurrence rates of NSCL/P in the total sample of subjects, as well as the two study groups (4mg, 0.4 mg) to that of a historical control group. The study has been approved by IRBs (ethics committees) of all involved sites. Results will be disseminated through publications and presentations at scientific meetings.

Vitamin B 12 deficiency is a common problem in elderly subjects. If a serum cobalamin level of about 150 pmol/L (200 pg/mL) is considered normal, 10 -15% of the elderly are deficient. Today, however, a threshold of 220 -258 pmol/L (300 -350 pg/mL) is recognized as desirable in the elderly, or else sensitive markers like the blood concentration of homocysteine or methylmalonic acid (MMA) are used. Then the prevalence of cobalamin deficiency rises to up to 43%. In the elderly, this high prevalence of poor cobalamin status is predominantly caused by atrophic gastritis type B. Atrophic gastritis results in declining gastric acid and pepsinogen secretion, and hence decreasing intestinal absorption of the cobalamin protein complexes from food. About 20 -50% of the elderly are affected. Furthermore, the reduced acid secretion leads to an alkalinization of the small intestine, which may result in bacterial overgrowth and thus to a further decrease of the bioavailability of the vitamin. In addition, some drugs such as proton pump inhibitors or H2 receptor antagonists inhibit the intestinal absorption of vitamin B 12 . An already moderately reduced vitamin B 12 level is associated with vascular disease and neurocognitive disorders such as depression and impaired cognitive performance. Furthermore, a poor vitamin B 12 status is assumed to be involved in the development and progression of dementia (e.g., Alzheimer's dementia). This is especially observable if the folic acid status is reduced as well. Due to the insecure supply, the cobalamin status of elderly persons (z60 years) should be regularly controlled and a general supplementation with vitamin B 12 (>50 Ag/day) should be considered.

Folic ;acid ( 5 mg) was given daily, for not less than one menstrual period before conception and until the tenth week of pregnancy, to 8 1 women (FS) with a history of a previous neural tube defect (NTD) birth. There was no NTD recurrence among this group or among the offspring of a further 20 women (PS) whose folic acid supplementation fell sh'ort of the full regime. In another I14 women who became pregnant without folic acid supplementation (IJS), there were four NTD recurrences (3.5 per cent). Our results suggest that folk acid supplementation might be an effective method of primary prevention of neural tube defects.

Background: Alzhcimcr's disease (AD) is the most common cause of cognitive impairment in older patients and is expected to increase greatly in prevalence. Interventions that could delay disease onset would have a major public health impact. Objective: The objective of this article is to review evidence from epidemiologic studies and controlled trials addressing whether AD can be prevented. Methods: Data were gathered through a comprehensive, systematic search of MEDLINE using focused search criteria and spanning a 6-year period from January 1998 through January 2004; a hand search of reference lists from these studies and reviews; a review of the Cochrane Database of Systematic Reviews; and a hand search of relevant journals. Selection of articles was based on the clinical focus. Additional inclusion criteria were used to select key articles that contained higher-level evidence in accordance with explicit, validated criteria. Results: Preventive interventions for AD include vitamins, nonsteroidal anti-inflammatory drugs, and agents that protect the endothelium (eg, statins). Good control of hypertension with angiotensinconverting enzyme inhibitors and long-acting dihydropyridines also confers neuroprotective benefits. Conclusions: The paradigm that AD is pharmacologically unresponsive is shifting as more effective pharmacotherapies for prevention and treatment rapidly emerge. Our understanding of the molecular mechanisms of neurodegeneration will soon allow us to more specifically target and interrupt the processes that contribute to this progressive dementia.

Maternal undernutrition and low macro- and micronutrient intake and weight gain during pregnancy have been reported in Bangladesh. We aimed to determine the effects of lipid-based nutrient supplements for pregnant and lactating women (LNS-PL) on weight gain and midupper arm circumference (MUAC) during pregnancy. The Rang-Din Nutrition Study, a cluster-randomized effectiveness trial conducted in Bangladesh, enrolled 4011 pregnant women at ≤20 wk gestation who received either 60 mg Fe + 400 μg folic acid/d or 20 g LNS-PL/d (118 kcal) containing essential fatty acids and vitamins and minerals until delivery. At 36 wk gestation, women were interviewed at home and then attended a follow-up examination at local clinics (n = 2877), where anthropometric measurements were taken. No significant differences between intervention groups in maternal weight gain per week, low weight gain per week, or MUAC at 36 wk gestation were observed in the full sample. However, among multiparous women aged ≥2...

Background: Folate deficiency is common in alcoholic patients, in part due to abnormal transport across membranes relevant to folate homeostasis. The reduced folate carrier (RFC) transports monoglutamyl folates across tissue membranes and could be affected by chronic exposure to ethanol. The micropig model is suitable to study the effect of alcoholism on RFC and folate transport across membranes.Methods: The membrane transport of [3H]-folic acid was measured by a vacuum filtration method in jejunal brush border (JBB), liver plasma membrane (LPM), and kidney brush border (KBB) membranes vesicles from micropigs fed control or 40% ethanol diets for 12 months. RFC transcripts were analyzed by reverse transcription polymerase chain reaction in jejunal mucosa, liver, and kidney from the same animals.Results: When we compared results from three relevant membranes in control animals, the transport of [3H]-folic acid was highest in LPM, 3-fold lower in KBB (p < 0.001), and 6-fold lower in JBB (p < 0.001). The concentration of RFC transcripts per total RNA was greatest in liver, followed by kidney and jejunum. The transport of [3H]-folic acid by JBB vesicles from chronic ethanol-fed animals exhibited 2-fold lower Km and Vmax (p < 0.05), whereas there was no ethanol effect on the Vmax of [3H]-folic acid transport by LPM or KBB. RFC transcript levels were 10-fold lower in jejunal mucosa from ethanol-fed animals than in control-fed animals (p < 0.005).Conclusions: Although our findings demonstrate different RFC transcript amounts and transport efficiencies among tissues, the present studies suggest that chronic ethanol exposure decreases the intestinal absorption of folic acid by altering the expression of RFC and consequently its transport kinetics in JBB. These findings provide a mechanism for the clinical finding of reduced folic acid absorption in chronic alcoholics.

The risk of colorectal cancer (CRC) may be influenced by aberrant DNA methylation and altered nucleotide synthesis and repair, possibly caused by impaired dietary folate intake as well as by polymorphic variants in one-carbon metabolism genes. A case–control study using seventy-one CRC patients and eighty unrelated healthy controls was carried out to assess the genetic association of fifteen SNP and one insertion in nine genes belonging to the folate pathway. Polymorphism selection was based on literature data, and included those which have a known or suspected functional impact on cancer and missense polymorphisms that are most likely to alter protein function. Genotyping was performed by real-time PCR and PCR followed by restriction analysis. The likelihood ratio statistic indicated that most of the polymorphisms were not associated with the risk of CRC. However, an increased risk of CRC was observed for two variant alleles of SNP mapping on the transcobalamin 2 gene (TCN2): C776G...

From the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Mass (PFJ, AGB, IHR, JS); the NHLBI Family Heart Study, University of Utah Cardiovascular Genetics Research Clinic, Salt Lake City (RRW); the NHLBI Family Heart Study, ...

BACKGROUND: 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 higher FA than the recommended intake for rodents had adverse effects on embryonic mouse development at embryonic days (E)10.5 and 14.5. In this report, we examined developmental outcomes in E14.5 embryos after administering a diet supplemented with 10-fold higher FA than recommended to pregnant mice with and without a mild deficiency of methylenetetrahydrofolate reductase (MTHFR). METHODS: Pregnant mice with or without a deficiency in MTHFR were fed a control diet (recommended FA intake of 2 mg/kg diet for rodents) or an FA-supplemented diet (FASD; 10-fold higher than the recommended intake [20 mg/kg diet]). At E14.5, mice were examined for embryonic loss and growth retardation, and hearts were assessed for defects and for ventricular wall thickness. RESULTS: Maternal FA supplementation was associated with embryonic loss, embryonic delays, a higher incidence of ventricular septal defects, and thinner left and right ventricular walls, compared to mothers fed control diet. CONCLUSIONS: Our work suggests that even moderately high levels of FA supplementation may adversely affect fetal mouse development. Additional studies are warranted to evaluate the impact of high folate intake in pregnant women. Birth Defects Research (Part A) 97:47À52, 2013.

Objective: To assess the effect on the haemoglobin concentrations of schoolchildren of weekly iron tablets administered by teachers. Design: Sixty schools were randomly assigned to two groups: in 30 schools children were given weekly for 10 weeks a tablet providing 65 mg of iron and 0.25 mg of folic acid; in the other 30 schools no iron tablets were given. All children were dewormed and given vitamin A before the study began. The haemoglobin concentration of up to 20 randomly selected children in each school was estimated before and 2 weeks after the end of treatment. Setting: Rural community schools in Kolondieba district of Mali. Subjects: Some 1113 schoolchildren aged 6-19 years with a mean of 11.4 years. Results: The haemoglobin concentration of treated children rose on average by 1.8 g l 21 ðP , 0:001Þ and the prevalence of anaemia fell by 8.2% ðP , 0:001Þ; in untreated children the haemoglobin concentration fell by an average of 22.7 g l 21 ðP , 0:001Þ and the prevalence of anaemia rose by 9.4% ðP , 0:001Þ. The fall in haemoglobin concentration among untreated girls of 24.0 g l 21 was greater than in untreated boys (20.3 g l 21 , P , 0:001). Conclusions: Weekly iron tablets given by teachers prevented a general fall in the haemoglobin concentrations of untreated children, and led to a small but statistically significant rise among treated children ðP , 0:001Þ. Young children benefited more than children aged $12 years, and girls benefited more than boys.

THE EPIDEMIC INCREASE in sexual activity and resultant pregnancies among adolescent girls has created a need for safe, convenient, effective forms of contraception. Among the options available, adolescents often prefer the use of the oral contraceptive pill, which substantially relieves menstrual cramps, regulates menses, frequently improves facial acne, and requires no motivation at the time of intercourse. These effects of pill usage, viewed as positive by teenagers, foster compliance. However, the pill is known to cause a wide variety of metabolic changes, including abnormalities in serum folate and red cell folate in women more than 20 years of age? This study was designed to determine if adolescents who take oral contraceptives are also susceptible to abnormal folate metabolism and resultant megaloblastic anemia.

Background: Low folate status is associated with poor cognitive function and dementia in the elderly. Since 1998, grain products in the United States have been fortified with folic acid, which has reduced the prevalence of folate deficiency and hyperhomocysteinemia. Objective: We investigated whether folate status is associated with cognitive function and dementia in a cohort of elderly Latinos (aged ͧ 60 y; n ҃ 1789) exposed to folic acid fortification. Design: Global cognitive function was assessed by the Modified Mini-Mental State Examination (3MSE) and specific cognitive functions by cross-culturally validated neuropsychological tests. Dementia was diagnosed according to the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, 3rd edition revised, and California Alzheimer Disease Diagnostic and Treatment criteria. Red blood cell (RBC) folate was measured by automated chemiluminescence and total plasma homocysteine by HPLC. Results: The prevalence of folate deficiency (RBC folate ͨ 160 ng/mL) was 1%. After control for confounding by homocysteine, vitamin B-12, creatinine, demographic variables, and depressive symptom score, RBC folate was directly associated with 3MSE (P ҃ 0.005) and delayed recall (P ҃ 0.007) scores. In addition, adjusted odds ratios for low 3MSE score (ͨ78) and dementia diagnosis per unit increase in RBC folate were significantly below unity (P ͨ 0.008), which indicated that the relative risks of cognitive impairment and dementia decreased with increasing RBC folate concentration. In contrast, adjusted odds ratios for low 3MSE score and dementia diagnosis per unit increase in homocysteine were not significant. Conclusion: RBC folate is directly associated with cognitive function scores and is inversely associated with dementia in elderly Latinos despite folic acid fortification.

The effect of triethyllead (TriEL) on motile activity, structure of cytoskeleton and chemotaxis of Dictyostelium discoideum amoebae in developing concentration gradients of folic acid (FA) and cAMP has been studied. It was observed that 3 mM TriEL had little or no effect on locomotion and chemotactic response of cells, whereas 5 mM TriEL strongly reduced the motile activity of Dictyostelium discoideum amoebae and inhibited their chemotaxis towards cAMP, but not towards FA. FA was found to restore the motile activity of Dictyostelium discoideum , inhibited by TriEL. A similar effect was observed in the presence of other antioxidants, i.e. ascorbic acid and sodium selenite, suggesting that oxidative stress may be involved in the action of TriEL. Moreover, the treatment of Dictyostelium amoebae with 5 mM TriEL caused disruption of microtubules while 3 mM TriEL had little effect on their structure. FA caused restoration of microtubules only in some cells within 1 h of incubation, i.e. when the directional movement of cells towards this chemoattractant was already observed. However, their organization was significantly different from that observed in the untreated cells, suggesting that microtubule undisturbed organisation may be not necessary for Dictyostelium discoideum amoebae locomotion and chemotaxis #

Indocyanine green (ICG) is a near-infrared (NIR) imaging agent and is also an ideal light absorber for laser-mediated photothermal therapy. This NIR dye could serve as a basis of a dualfunctional probe with integrated optical imaging and photothermal therapy capabilities. However, applications of ICG remain limited by its concentration-dependent aggregation, poor aqueous stability, nonspecific binding to proteins and lack of target specificity. To overcome these limitations, a novel ICG-containing nanostructure is designed utilizing the noncovalent self-assembly chemistry between phospholipid-polyethylene glycol (PL-PEG) and ICG. The interactions between both amphiphilic ICG and PL-PEG were studied using absorption and fluorescence spectroscopy. The properties of ICG-PL-PEG nanoprobe, such as absorption and fluorescence spectra, stability, morphology and size distribution, were also investigated. Two representative targeting molecules, namely, a small molecule, folic acid (FA), and a large protein, integrin R v β 3 monoclonal antibody (mAb), were conjugated to the surface of ICG-PL-PEG nanoprobe, displaying the diversity of ligand conjugation. The target specificity was confirmed using three cell lines with different levels of available folate receptors (FRs) or integrin R v β 3 expression via laser scanning confocal microscope and flow cytometry. This targeting ICG-PL-PEG nanoprobe could be internalized into targeted cells via ligand-receptor mediated endocytosis pathway. Our in vitro experiments showed that internalized ICG-PL-PEG could be used for cell imaging and selective photothermal cell destruction. These results represent the first demonstration of the dual functionality of ICG-containing nanostructure for targeted optical imaging and photothermal therapy of cancerous cells. This novel ICG-PL-PEG nanostructure, when conjugated with other therapeutic and imaging agents, could become a multifunctional probe for cancer diagnosis and treatment.

Background: Epidemiologic evidence regarding niacin, folate, vitamin B-6, and vitamin B-12 intake in relation to cognitive function is limited, especially in midlife.Objective: We hypothesize that higher intake of these B vitamins in young adulthood is associated with better cognition later in life.Design: This study comprised a community-based multicenter cohort of black and white men and women aged 18-30 y in 1985-1986 (year 0, i.e., baseline) from the Coronary Artery Risk Development in Young Adults (CARDIA) study (n = 3136). We examined participants&#39; CARDIA diet history at years 0, 7, and 20 to assess nutrient intake, including dietary and supplemental B vitamins. We measured cognitive function at year 25 (mean ± SD age: 50 ± 4 y) through the use of the Rey Auditory Verbal Learning Test (RAVLT) for verbal memory, the Digit Symbol Substitution Test (DSST) for psychomotor speed, and a modified Stroop interference test for executive function. Higher RAVLT and DSST scores and a ...

Objectives: Elevated homocysteine has emerged as a risk factor for cognitive impairment even in healthy elderly persons. Reduced brain volume and white matter hyperintensities also occur in healthy elderly as well, but the interrelationships between these have not been well studied. We report these interrelationships in non demented, relatively healthy, community-dwelling older adults from a single East Asian population. Methods: Two hundred twenty-eight right-handed participants age 55 years and above were evaluated. Persons with medical conditions or neurological diseases other than well-controlled diabetes mellitus and hypertension were excluded. Participants underwent quantitative magnetic resonance imaging of the brain using a standardized protocol and neuropsychological evaluation. Plasma homocysteine, folate, vitamin B 12 , and markers for cardiovascular risk: blood pressure, body mass index, fasting blood glucose, and lipid profile were measured. Results: Elevated homocysteine was associated with reduced global cerebral volume, larger ventricles, reduced cerebral white matter volume, and lower cognitive performance in several domains. Elevated homocysteine was associated with reduced white matter volume (β = −20.80, t = −2.9, df = 223, p = 0.004) and lower speed of processing (β = −0.38, t = −2.1, df = 223, p = 0.03), even after controlling for age, gender, and education. However, the association between homocysteine and lower speed of processing disappeared after controlling for white matter volume. Elevated homocysteine was not associated with white matter hyperintensity volume or with hippocampal volume. Although homocysteine and folate levels were correlated, their effects on white matter volume were dissociated. Conclusion: In non demented, relatively healthy adults, elevated homocysteine is associated with lower cognitive scores and reduced cerebral white matter volume. These effects can be dissociated from those related to white matter hyperintensities or reduced folate level. (AM J Geriatr Psychiatry 2012; 00:1-9)

This article describes the preparation of a graphene electrode modified with a new conjugate of peptide nanotubes and folic acid for the selective detection of human cervical cancer cells over-expressing folate receptors. The functionalization of peptide nanotubes with folic acid was confirmed by fluorescence microscopy and atomic force microscopy. The peptide nanotube-folic acid modified graphene electrode was characterized by scanning electron microscopy and cyclic voltammetry. The modification of the graphene electrode with peptide nanotube-folic acid led to an increase in the current signal. The human cervical cancer cells were bound to the modified electrode through the folic acid-folate receptor interaction. Cyclic voltammograms in the presence of [Fe(CN) 6 ] 3À/4À as a redox species demonstrated that the binding of the folate receptor from human cervical cancer cells to the peptide nanotube-folic acid modified electrode lowered the electron transfer resulting in a decrease in the measured current. A detection limit of 250 human cervical cancer cells per mL was obtained. Control experiments confirmed that the peptide nanotube-folic acid electrode specifically recognized folate receptors. The modified electrode described here opens up new possibilities for future applications in early stage diagnoses of diseases where cells over-express folate receptors, such as in cancer or leishmaniasis disease.

Neural tube defects are important causes of infant mortality and childhood morbidity. We investigated the relationship between zinc, selenium, copper, and lead concentrations and neural-tube-defect occurrence in women with a second-trimester termination due to fetal-neural-tube defects (NTDs) in this case-control study. Fourteen pregnant women whose pregnancies were terminated as a result of second-trimester ultrasonographic diagnosis of neural tube defects were recruited as cases. The control group (n = 14) consisted of women who were selected among age-, gravidity-, and socioeconomic state (SES)-matched women who had a normal triple-screen and targeted ultrasound during the second trimester with documented normal fetal outcome. Zinc and copper determinations were made using flame atomic absorption spectrophotometer (AAS). Graphite furnace AAS was used for Pb, and Se levels were measured with hydride generation AAS. Cases had significanltly low serum zinc and selenium levels (62.48±15.9 vs 102.6±23.7 and 55.16±11.3 vs 77.4±5.5, respectively, p<0.001). Serum Cu and whole-blood Pb levels were significantly high when compared to controls. There was a negative correlation between serum zinc and selenium levels, and serum copper levels (r=-425 and

Purpose Cardiovascular risk factors such as elevated levels of asymmetric dimethylarginine (ADMA)/C-reactive protein (CRP) and homocysteine are potentially related to essential micronutrients such as certain B vitamins and antioxidant vitamins. The aim of the present study was to investigate whether supplementation with moderate doses of B vitamins and/or antioxidants could alter either ADMA and/or CRP concentrations in middle-aged, apparently healthy men with mildly elevated homocysteine levels. Methods A randomised, double-blind, factorial design, intervention study was carried out on 132 men with mildly elevated homocysteine levels, allocated to four groups (a) B vitamins alone-1 mg folic acid, 7.2 mg pyridoxine, 0.02 mg cyanocobalamin daily, (b) antioxidants alone-150 mg ascorbic acid, 67 mg vitamin E, 9 mg b-carotene daily, (c) B vitamins with antioxidant vitamins, or (d) placebo. A total of 101 men completed the study to 8 weeks.

Anemia and micronutrient deficiencies are common among Indian schoolchildren. We assessed the effectiveness of micronutrient fortification of meals cooked and fortified at school on anemia and micronutrient status of schoolchildren in Himalayan villages of India. In this placebo-controlled, cluster-randomized study, 499 schoolchildren (6-10 y) received either multiple micronutrients (treatment group) or placebo (control group) as part of school meals (6 d/wk) for 8 mo. Both groups were dewormed at the beginning of the study. The micronutrient premix provided 10 mg iron, 375 mg vitamin A, 4.2 mg zinc, 225 mg folic acid, and 1.35 mg vitamin B-12 for each child per day (;75% recommended dietary allowance). Blood samples drawn before and after the intervention were analyzed for hemoglobin, ferritin, retinol, zinc, folate, and vitamin B-12. Baseline prevalence of anemia (37%), iron deficiency anemia (10%), low serum ferritin (24%), retinol (56%), zinc (74%), folate (68%), and vitamin B-12 (17%) did not differ between groups. Postintervention, fewer in the treatment group had lower serum retinol [odds ratio (OR) (95% CI): 0.57 (0.33-0.97)] and folate [OR (95% CI): 0.47 (0.26-0.84)] than the control group. The serum vitamin B-12 concentration decreased in both groups, but the magnitude of change was less in the treatment than in the control group (P , 0.05). Total body iron (TBI) increased in both groups; however, the change was greater in the treatment than in the control group (P , 0.05). Micronutrient fortification of school meals by trained school personnel was effective in improving vitamin A, folate, and TBI status while also reducing the magnitude of a decrease in vitamin B-12 status.

Deficiencies of micronutrients (zinc, iron, folic acid and iodine) during pregnancy are known causes of Low Birth Weight (LBW). Studies have documented status of one or two micronutrients amongst pregnant women (PW). However, no attempt has been made to concurrently assess the prevalence of multiple micronutrient deficiencies and the factors associated with them amongst PW.Objective: The present study was undertaken to assess the prevalence of multiple micronutrient deficiencies amongst PW in a rural area.Methods: A community based cross sectional survey was conducted in six villages of a rural area of district Faridabad in Haryana state, India during November 2000 and October 2001. All PW aged 18 years or more, with pregnancy duration of more than 28 weeks were enrolled. Data were collected on socio-economic status and other demographic parameters. Serum zinc, copper and magnesium levels were estimated by utilizing the Atomic absorption spectrophotometry (AAS); serum ferritin and folate was estimated by Enzyme Linked Immuno Sorbent Assay (ELISA) method and the Radio-lmmuno Assay (RIA) method, respectively and serum thyroid stimulating hormone (TSH) level was estimated by the Abbot AxSYM System. Serum zinc, copper, magnesium, ferritin, and folate levels less than 70.0 μg/dl, 80.0 μg/dl, 1.80 mg/dl, 15 ng/ml, and 3 ng/ml, respectively were considered as indicative of deficiency for respective micronutrients. The TSH levels of 4.670 and more indicated iodine deficiency status. Dietary intake of micronutrients was assessed utilizing 1-day 24-hour dietary recall methodology. Food consumption pattern was assessed utilizing the food frequency questionnaire methodology.Results: Nearly 73.5, 2.7, 43.6, 73.4, 26.3, and 6.4 percent PW were deficient in zinc, copper, magnesium, iron, folic acid and iodine, respectively. The highest concurrent prevalence of two, three, four and five micronutrient deficiency was of zinc and iron (54.9%); zinc, magnesium and iron (25.6%); zinc, magnesium, iron and folic acid (9.3%) and zinc, magnesium, iron, folic acid and iodine (0.8%), respectively. No pregnant woman was found to have concomitant deficiencies of all the six micronutrients. Dietary intake data revealed an inadequate nutrient intake. Over 19% PW were consuming less than 50% of the recommended calories. Similarly, 99, 86.2, 75.4, 23.6, 3.9 percent of the PW were consuming less than 50% of the recommended folic acid, zinc, iron, copper, and magnesium. The consumption of food groups rich in micronutrients (pulses, vegetables, fruits, nuts and oil seeds, animal foods) was infrequent. Univariate and Multivariate logistic regression analysis revealed that low dietary intake of nutrients, low frequency of consumption of food groups rich in micronutrients and increased reproductive cycles with short interpregnancy intervals were important factors leading to micronutrient deficiencies.Conclusion: There was a high prevalence of micronutrient deficiencies amongst the PW of the area, possibly due to the poor dietary intake of food and low frequency of consumption of food groups rich in micronutrients. The concurrent prevalence of two, three, four and five micronutrient deficiencies were common.

The amino acid homocysteine (Hcy), formed from methionine has profound importance in health and diseases. In normal circumstances, it is converted to cysteine and partly remethylated to methionine with the help of vit B12 and folate. However, when normal metabolism is disturbed, due to deficiency of cystathionine-beta-synthase, which requires vit B6 for activation, Hcy is accumulated in the blood with an increase of methionine, resulting into mental retardation (homocystinuria type I). A decrease of cysteine may cause eye diseases, due to decrease in the synthesis of glutathione (antioxidant). In homocystinurias type II, III and IV, there is accumulation of Hcy, but a decrease of methionine, thus, there is no mental retardation. Homocysteinemia is found in Marfan syndrome, some cases of type I diabetes and is also linked to smoking and has genetic basis too. In hyperhomocysteinemias (HHcys), clinical manifestations are mental retardation and seizures (type I only), ectopia lentis, s...

Boron neutron capture therapy (BNCT) is increasingly being used in the treatment of several aggressive cancers, including cerebral glioblastoma multiforme. The main requirement for this therapy is selective targeting of tumor cells by sufficient quantities of 10 B atoms required for their capture/irradiation with lowenergy thermal neutrons. The low content of boron targeting species in glioblastoma multiforme accounts for the difficulty in selective targeting of this very malignant cerebral tumor by this radiation modality. In the present study, we have used for the first time boron nitride nanotubes as carriers of boron atoms to overcome this problem and enhance the selective targeting and ablative efficacy of BNCT for these tumors. Following their dispersion in aqueous solution by noncovalent coating with biocompatible poly-L-lysine solutions, boron nitride nanotubes were functionalized with a fluorescent probe (quantum dots) to enable their tracking and with folic acid as selective tumor targeting ligand. Initial in vitro studies have confirmed substantive and selective uptake of these nanovectors by glioblastoma multiforme cells, an observation which confirms their potential clinical application for BNCT therapy for these malignant cerebral tumors.

BACKGROUND: Folate metabolism pathway genes have been examined for association with neural tube defects (NTDs) because folic acid supplementation reduces the risk of this debilitating birth defect. Most studies addressed these genes individually, often with different populations providing conflicting results. OBJECTIVES: Our study evaluates several folate pathway genes for association with human NTDs, incorporating an environmental cofactor: maternal folate supplementation. METHODS: In 304 Caucasian American NTD families with myelomeningocele or anencephaly, we examined 28 polymorphisms in 11 genes: folate receptor 1, folate receptor 2, solute carrier family 19 member 1, transcobalamin II, methylenetetrahydrofolate dehydrogenase 1, serine hydroxymethyltransferase 1, 5,10-methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homocysteine methyltransferase, 5-methyltetrahydrofolate-homocysteine methyltransferase reductase, betaine-homocysteine methyltransferase (BHMT), and cystathionine-beta-synthase. RESULTS: Only single nucleotide polymorphisms (SNPs) in BHMT were significantly associated in the overall data set; this significance was strongest when mothers took folate-containing nutritional supplements before conception. The BHMT SNP rs3733890 was more significant when the data were stratified by preferential transmission of the MTHFR rs1801133 thermolabile T allele from parent to offspring. Other SNPs in folate pathway genes were marginally significant in some analyses when stratified by maternal supplementation, MTHFR, or BHMT allele transmission. CONCLUSIONS: BHMT rs3733890 is significantly associated in our data set, whereas MTHFR rs1801133 is not a major risk factor. Further investigation of folate and methionine cycle genes will require extensive SNP genotyping and/or resequencing to identify novel variants, inclusion of environmental factors, and investigation of gene-gene interactions in large data sets. KEY WORDS: folate, folic acid supplementation, genetic association, neural tube defects. Environ Health Perspect 114:1547-1552 (2006). doi:10.1289/ehp.9166 available via http://dx.doi.org/ [Online 15 June 2006]

Small size at birth continues to be a problem worldwide and many factors, including reduced folate intake and Pb exposure, are associated with it. However, single factors rarely explain the variability in birth weight, suggesting a need for more complex explanatory models. We investigated environment-gene interactions to understand whether folate intake and maternal Pb exposure were associated with smaller newborn size in 474 women with uncomplicated pregnancies delivering term infants in Mexico City. We examined if folate intake modified the negative effects of maternal Pb burden on birth size. We also asked if maternal and infant methylenetetrahydrofolate reductase (MTHFR) genotypes (C677T, A1298C and G1793A) modified the effects of folate intake or Pb exposure on birth size. Women were aged 24·6 (SD 5·1) years; 43·5 % were primiparous. Maternal blood Pb at delivery was 86 (SD 42) μg/l, with 26·7 % having levels ≥100 μg/l. Tibia Pb level was 9·9 (SD 9·8) μg/g. Of the women, 35·3 % had folate intakes <400 μg/d. Birth weight was 3170 (SD 422) g. In covariate-adjusted regressions, higher folate intake was associated with higher birth weight (β 0·04; P<0·05). Higher bone Pb was associated with lower birth weight (β −4·9; P<0·05). Folate intake did not modify the effects of Pb on birth size, nor did MTHFR modify the association between Pb or folate intake on birth size. Although modest, the relationship between maternal nutrition, Pb burden and birth size does underscore the importance of environmental exposures to child health because patterns of fetal growth may affect health outcomes well into adulthood.

WHAT'S KNOWN ON THIS SUBJECT: Fetal neurocognitive development can be compromised by insufficient intake of folate and other nutrients, but it is not known whether folate intake during adolescence affects cognitive development and academic achievements of adolescents.

A new spectrofl uorimetric method was reported for the determination of folic acid (FA), based on its quenching eff ect on the fl uorescence intensity of Tb 3+ -1,10-phenanthroline complex as a fl uorescent probe. The quenched fl uorescence intensity at an emission wavelength of 545 nm was proportional to the concentration of FA in Tris-HCl buff er solution of pH 6.2. The eff ects of pH, time, order of addition of reagents, temperature and concentrations of Tb 3+ , buff er and 1,10-phenanthroline were investigated and optimized. The linear range for the determination of FA was 0.01-1.1 mg/L. The detection limit was 0.003 mg/L and the relative standard deviation for replicated determination of 1 mg/L of folic acid was 1.2%. This method was simple, practical and relatively free from interference eff ects. It was successfully applied to assess FA in pharmaceutical tablets and urine samples.

To verify the efficacy of a patented proprietary combination of nutraceuticals containing natural hypocholesterolemic and antioxidant agents as red yeast rice extract, policosanols, coenzyme Q 10 , astaxanthin, and folic acid in the following subgroups of hyperlipidemic subjects: fertile (F) versus menopause (M) women, adults versus elderly ([65 years), lunch versus dinner administration time. A randomised, multicenter study in 411 Italians units compared Armolipid-Rottapharm|Madaus (ARM) one tablet/day plus diet versus diet alone (D) for 16 weeks in hyperlipidemic patients [serum total cholesterol (tot-C) [200 mg/dL or LDL-cholesterol (LDL-C) [150 mg/dL at admission]. Efficacy parameters were measured at baseline and every 4 weeks. In 2,408 eligible subjects, 1,665 adults and 743 elderly, total and LDL-cholesterol were likewise reduced by ARM ? D in both age classes and significantly versus D. In 1,246 cases, 302 F and 946 M, tot-C gradually and significantly decreased up to 18.7 and 16.8% in F and M treated groups versus 9% in D group. Similar reduction was observed in LDL-C. In 907 cases, the time of administration of ARM was detailed: 733 received ARM ? D at dinner and 174 at lunch. Cholesterolemia improved equally in the two groups. The association of ARM with an appropriate diet is more effective than diet alone in reducing abnormal cholesterolemia, independently from age classes and administration time during the day, supporting its positive use for controlling hypercholesterolemia with a positive impact on CHD prevention in all categories of subjects.

hypertension, left ventricular function, age, diabetes and history of previous stroke. 1 Following this, the patient's potential benefit from antiplatelet therapy and OAC should be estimated. Finally, and perhaps most tricky, the patient's risk of major bleeding should be assessed. Future research should try to develop more robust methods to predict the individual risk of stroke and major bleeding.

Micronutrient deficiencies, especially iron-deficiency anemia, are a public health problem in Egypt, where anemia rates almost doubled in the years from 2000 to 2005. In 2008, the Government of Egypt began implementation of a 5-year national program to fortify with iron and folic acid the wheat flour used in baking subsidized baladi bread, the staple food consumed by a majority of low- income groups. To project the achievements of this national Wheat Flour Fortification Program. This paper describes the program, estimates the production of fortified flour and consumption of fortified bread, and identifies program challenges and sustainability issues. Through the national Wheat Flour Fortification Program, ferrous sulfate and folic acid are now added to all wheat flour produced under the national Food Subsidy Program. Up to 50 million Egyptians nationwide are now consuming quality-assured fortified baladi bread on a daily basis. In 2011, 6.5 million MT of fortified wheat flour was pr...

Background: Anaemia during pregnancy can lead to adverse maternal and perinatal outcomes. The WHO recommends that all pregnant women in areas where anaemia is prevalent receive supplements of iron and folic acid. However, due to many factors, the use of iron and folic acid supplementation is still low in many countries. This study was conducted to assess the rates of iron-folic supplementation and the associated factors during pregnancy and the effects of taking iron-folic acid supplementation on rates of maternal anaemia and low birth weight (LBW) infants.

Recent studies have demonstrated that cholestyramine, an anionic exchange resin, binds inorganic and hemoglobin iron in vitro and inhibits the absorption of these compounds from the rat small intestine. However, these studies did not answer the question: Will prolonged cholestyramine administration cause depletion of iron stores and development of iron deficiency anemia? Accordingly, rats were fed diets of standard rat chow or standard rat chow-containing either 2 or 5% cholestyramine for 6 months. In the 5% cholestyramine group the hematocrit and hemoglobin values were significantly lower as compared to controls (37.5 vs 43.6%; P<0.001) and 11.4 vs 14.2 g%; g<0.001). Serum iron values in the 5% cholestyramine groups were significantly less than the control group (158 ± 23 vs 205 ± 15 #g%; P<0.001). In the control group nonheme iron in the liver, spleen and duodenum was 206 ~: 31, 1482 ± 212 and 12.5 ± 1.1 #g/g tissue, respectively. In the 2% cholestyramine-treated group, liver nonheme iron was reduced to 172 ± 33 #g/g, spleen nonheme iron to 1266 ± 447 #g/g and duodenal iron to 11.7 ± 1.0 #g/g. In the 5% cholestyramine-treated group liver nonheme iron was significantly reduced to 143 ± 35 ~g/g, spleen nonheme iron to 1030 ± 3.4 #g/g and duodenal nonheme iron to 10.2 ± 1.4 #g/g respectively. In addition, a significant decrease in serum vitamin B12 levels was noted in cholestyramine-fed rats compared to controls (256 ± 83 vs 404 ± 118 ##g/ml). These data indicate that prolonged administration of cholestyramine to rats results in significantly decreased serum iron, tissue nonheme iron stores and serum vitamin B12 levels associated with decreased hematocrit and hemoglobin levels.