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Milk can be considered as an indicator of the degree of environmental contamination of the place where it is produced and this is especially important when assessing its content in toxic metals. Therefore, 36 bovine milk samples from 7 farms with a semi-extensive grazing system were analysed, located in Asturias (Spain), in an area with high probability of being highly contaminated due to a mining zone, with important industrial activity and near high-density highway traffic. The samples were lyophilised to achieve total dehydration, further analysed using inductively coupled plasma mass spectrometry (ICP-MS). The metals titrated were aluminium (Al), arsenic (As), molybdenum (Mo) and mercury (Hg) in the lyophilised samples and subsequently extrapolated their values to whole milk. All samples analysed showed levels of Al and Mo above the limit of detection, with mean values of Al of 140.89 ± 157.07 in liquid milk and 1065.76 ± 1073.45 in lyophilised milk and Mo of 20.72 ± 14.61 μg/kg and 152.26 ± 96.82 μg/kg in whole and lyophilised milk. Only As was detected in four samples with mean values of 18.45 ± 6.89 and 166.45 ± 42.30 μg/kg in liquid and lyophilised milk, respectively, and no Hg was found in any of them. In no case do the values found indicate a significant hazard to the population and are in agreement with those found in other investigations. Although the various anthropogenic activities of the area (industrial, mining, traffic density) could, a priori, indicate a possibly contaminated area.

In this case report, we analyze the possible causes of the poor health status of a professional Apis mellifera iberiensis apiary located in Gajanejos (Guadalajara, Spain). Several factors that potentially favor colony collapse were identified, including Nosema ceranae infection, alone or in combination with other factors (e.g., BQCV and DWV infection), and the accumulation of acaricides commonly used to control Varroa destructor in the beebread (coumaphos and tau-fluvalinate). Based on the levels of residues, the average toxic unit estimated for the apiary suggests a possible increase in vulnerability to infection by N. ceranae due to the presence of high levels of acaricides and the unusual climatic conditions of the year of the collapse event. These data highlight the importance of evaluating these factors in future monitoring programs, as well as the need to adopt adequate preventive measures as part of national and international welfare programs aimed at guaranteeing the health and fitness of bees., This research was funded by INIA-FEDER (RTA2017-00004-C02)

We developed a comprehensive composition database of 629 cereal-based gluten free (GF) products available in Spain. Information on ingredients and nutritional composition was retrieved from food package labels. GF products were primarily composed of rice and/or corn flour, and 90% of them included added rice starch. The most common added fat was sunflower oil (present in one third of the products), followed by palm fat, olive oil, and cocoa. Only 24.5% of the products had the nutrition claim &ldquo, no added sugar&rdquo, Fifty-six percent of the GF products had sucrose in their formulation. Xanthan gum was the most frequently employed fiber, appearing in 34.2% of the GF products, followed by other commonly used such as hydroxypropyl methylcellulose (23.1%), guar gum (19.7%), and vegetable gums (19.6%). Macronutrient analysis revealed that 25.4% of the products could be labeled as a source of fiber. Many of the considered GF food products showed very high contents of energy (33.5%), fats (28.5%), saturated fatty acids (30.0%), sugars (21.6%), and salt (28.3%). There is a timid reformulation in fat composition and salt reduction, but a lesser usage of alternative flours and pseudocereals.

En: Foods. 2021. vol. 10 (4) : 851. e-ISSN 2304-8158 We developed a new database to evaluate the nutritional composition of lactose-free products from Spain. The database includes dairy products and other products, all of which show the “lactose-free” declaration on their label, accounting for 327 products in total. Of these, 123 are dairy products, 16 are non-dairy products which include a dairy ingredient (5%) and 188 items (57% of the sample) are non-dairy products that do not contain any dairy ingredient. The main subgroups are yogurt (25%), milk (24%), and cheese (17%). Nineteen percent of the compiled products included nutritional claims on their labels. Most lactose-free products did not contain either added sugars or low- or no-calorie sweeteners (58%), while 34% included added sugars and only 6%, sweeteners or a combination of both (2%). We found that 19.5%, mainly within the milk subgroup, were fortified with vitamins A, D, E, K, B9 , and B12, P, and Ca. There were no significant differences in the nutritional composition between lactose-free products and traditional products. According to the NOVA classification, 55% of compiled lactose-free products were ultra-processed, and 20% processed. The array of lactose-free products marketed in Spain proves that there are enough, both in quantity and quality, to satisfy the dairy needs of lactose intolerants.

Arsenic is a toxic element widely distributed in nature, but numerous bacteria are able to resist its toxicity mainly through the ars genes encoding an arsenate reductase and an arsenite efflux pump. Some “arsenotrophic” bacteria are also able to use arsenite as energy supplier during autotrophic growth by coupling anaerobic arsenite oxidation via the arx gene products to nitrate respiration or photosynthesis. Here, we have demonstrated that Azoarcus sp. CIB, a facultative anaerobic β-proteobacterium, is able to resist arsenic oxyanions both under aerobic and anaerobic conditions. Genome mining, gene expression, and mutagenesis studies revealed the presence of a genomic island that harbors the ars and arx clusters involved in arsenic resistance in strain CIB. Orthologous ars clusters are widely distributed in the genomes of sequenced Azoarcus strains. Interestingly, genetic and metabolic approaches showed that the arx cluster of the CIB strain encodes an anaerobic arsenite oxidase also involved in the use of arsenite as energy source. Hence, Azoarcus sp. CIB represents the prototype of an obligate heterotrophic bacterium able to use arsenite as an extra-energy source for anaerobic cell growth. The arsenic island of strain CIB supports the notion that metabolic and energetic skills can be gained by genetic mobile elements.

Polymers with nanoparticle inclusions are attractive materials because physical properties can be tuned by varying size and volume fraction range. However, elastic behavior can degrade at higher inclusion fractions when particle-particle contacts become important, and sophisticated measurement techniques are required to study this crossover. Here, we report on the mechanical properties of materials with BaTiO3 nanoparticles (diameters

Polymer-tethered colloidal particles (aka "particle brush materials") have attracted interest as a platform for innovative material technologies and as a model system to elucidate glass formation in complex structured media. In this contribution, Brillouin light scattering is used to sequentially evaluate the role of brush architecture on the dynamical properties of brush particles in both the individual and assembled (film) state. In the former state, the analysis reveals that brush-brush interactions as well as global chain relaxation sensitively depend on grafting density; i.e., more polymer-like behavior is observed in sparse brush systems. This is interpreted to be a consequence of more extensive chain entanglement. In contrast, the local relaxation of films does not depend on grafting density. The results highlight that relaxation processes in particle brush-based materials span a wider range of time and length scales as compared to linear chain polymers. Differentiation between relaxation on local and global scale is necessary to reveal the influence of molecular structure and connectivity on the aging behavior of these complex systems.

Patients who follow a gluten-free diet (GFD) may be prone to nutritional deficiencies, due to food restriction and consumption of gluten-free products. The aim was to assess nutritional status in celiac children and adolescents on a long-term GFD. A cross-sectional age and gender-matched study in 70 celiac and 67 non-celiac volunteers was conducted, using dietary, anthropometric, biochemical parameters, and assessing bone mineral density and physical activity. Adequacy of vitamin D intake to recommendations was very low, in both groups, and intakes for calcium and magnesium were significantly lower in celiac volunteers. Celiac children and adolescents may have a higher risk of iron and folate deficiencies. Both groups followed a high-lipid, high-protein, low fiber diet. Median vitamin D plasma levels fell below reference values, in celiac and non-celiac participants, and were significantly lower in celiac girls. Other biochemical parameters were within normal ranges. Anthropometry and bone mineral density were similar within groups. With the exception of some slightly lower intakes, children and adolescents following a GFD appear to follow the same trends as healthy individuals on a normal diet. No effect of food restriction or gluten-free product consumption was observed.

Background. Angiogenesis has a key role in several conditions and is regulated by several factors such as the platelet-derived growth factor (PDGF) or the vascular endothelial growth factor (VEGF). The goal of this study was to investigate the possible role of PDGF and VEGF in a group of patients with severe food allergy.Methods. We design a prospective longitudinal study (n=30) with patients with persistent cow’s milk proteins (CMP) allergy. After achieving a CMP rush desensitization protocol, a clinical followup including SPT and blood samples to determine sIgE, protein levels, PDGF, and VEGF-A and a panel of the most representative Th1, Th2, Treg, and Th17cytokines were also monitored.Results. Baseline levels of PDGF and VEGF in the CMP allergic patients (1170 pg/mL and 253 pg/mL) were different compared to those nonallergic CMP control subjects (501 pg/mL and 108 pg/mL). Both PDGF and VEGF were significantly downregulated (P<0.05) 6 months after completion of the CMP desensitization process and remained significantly decreased 12 months later.Conclusion. The present study shows a significant increase of PDGF and VEGF in anaphylaxis suffering children compared to a control group. Interestingly, both VEGF and PDGF were significantly downregulated after completing a full CMP rush IgE desensitization.

Background Plasma concentrations of lipoprotein (a) (Lp(a)), a lipoprotein with atherogenic and thrombogenic properties, have a strong genetic basis, although high concentrations of Lp(a) have also been reported in the context of inflammation, as in rheumatoid arthritis (RA). Few studies evaluate the impact of biologic therapies (BT) on Lp(a) in RA, taking into account that with these new therapies a better control of inflammation is achieved. Objective The aim of the study was to evaluate the plasma concentrations of Lp(a) in Spanish RA patients on BT attending rheumatology outpatient clinics. Methods Baseline analysis of the CARdiovascular in rheuMAtology project, a 10-year prospective study, evaluating the risk of cardiovascular events in RA and other forms of inflammatory arthritis. RA patients were classified according to treatment: no biologic, anti-tumor necrosis factor, anti-interleukin-6 receptor tocilizumab (TCZ), and other biologic (rituximab or abatacept). A model of linear multivariate regression was built in which the dependent variable was Lp(a) concentration and the explanatory variable was BT. The model was adjusted for confounding factors. Results Seven hundred and seventy-five RA patients were analyzed. Plasma concentrations of total cholesterol and triglyceride were significantly higher in TCZ-treated patients. Nevertheless, no significant difference in the atherogenic index between TCZ-treated patients and patients without BT was found. After adjusting for confounding factors, patients with BT had lower concentrations of Lp(a) than those without BT; however, only TCZ-treated patients achieved statistically significant differences (?: ?0.303, 95% confidence interval: ?0.558 to ?0.047; P = .02). Conclusions RA patients treated with TCZ show lower plasma concentrations of Lp(a) compared with patients without BT. This project has been supported by an unrestricted grant from Abbvie, Spain. The design, analysis, interpretation of results, and preparation of the article have been done independently of Abbvie. Dr González-Gay's studies have been supported by grants from “Fondo de Investigaciones Sanitarias” PI06/0024, PS09/00748, and PI12/00060 and RD12/0009/0013 (RIER) from “Instituto de Salud Carlos III” (ISCIII) (Spain).

[Background] Cow’s milk protein allergy (CMPA) is the most common food allergy in infants. However, little is known about which specific immune mechanisms are related with the CMPA onset. The objective was to investigate which immune alterations constitute differential factors between allergy and tolerance, and hence could be implicated in the CMPA establishment in infants., [Methods] An extensive analysis of immune subsets, including Treg and cytokine-secreting cells was performed in blood samples from 28 infants younger than 9 mo obtained 1–4 d after the first adverse reaction to milk., [Results] Less than 4 d after first allergic reaction, infants who developed CMPA had decreased Treg counts and increased frequency of IL4-secreting CD4 T cells compared to controls. The deficit of Tregs was correlated with decreased serum levels of vitamin D. Values of Tregs, IL4-secreting cells and vitamin D were good predictors of CMPA diagnosis. Basal vitamin D levels in CMPA infants also predicted those CMPA patients developing spontaneous tolerance in the first year., [Conclusion] Establishment of CMPA in infants was related with lower Treg and vitamin D levels. These immune alterations would be crucial factors behind the CMPA establishment and they could constitute a therapeutic target for treatment of CMPA., This work was supported by grants from Instituto de Salud Carlos III (ISCIII) co-financed by FEDER funds (PI12/00934; ICI14/00282), and by a grant from Sociedad Española de Inmunología Clínica, Alergología y Asma Pediátrica (SEICAP). R.C-R. is supported by the ISCIII through the “Miguel Servet II” program (CPII13/00033), and M.P. by the Spanish MICINN through the Ramón y Cajal Program (RYC-2009–05486). J.L-A. is supported by an IISGM pre-doctoral grant, and L.P. is in receipt of a FPU PhD Grant (AP2012-2343) from the Ministerio de Educación, Cultura y Deporte (Spain).

Introduction. Folic acid (FA) is a synthetic compound commonly added for voluntary fortification of food products in many European countries. In our country, food composition databases (FCDB) lack comprehensive data on FA fortification practices and this is considered a priority research need when undergoing nutritional assessment of the population. Methods. A product inventory was collected and updated by visiting retail stores in Madrid Region, conducting online supermarket searches, and by the provision of food label information by manufacturers. Euro-FIR FCDB guidelines for data compilation and harmonization were used. Results. The FCDB, compiled between 2011 and 2015, includes FA as well as macro and micronutrient data from 338 fortified foodstuffs. As compared to previous FCDB updates (May 2010), 37 products have ceased to declare added FA in their labels, mainly yogurt and fermented milk products. The main food subgroup is ‘breakfast cereals’ (n = 95, 34% of total). However, the highest average FA fortification levels per recommended serving were observed in the ‘milk, milk products, and milk substitutes’ group at ≥35% FA Nutrient Reference Values (NRV, 200 µg, EU Regulation 1169 of 2011) (60–76.3 µg FA per 200 mL). Average contribution to the FA NRV per food group and serving ranged between 16%–35%. Conclusion. Our data show a minor decrease in the number of FA fortified products, but vitamin levels added by manufacturers are stable in most food groups and subgroups. This representative product inventory comprises the main FA food source from voluntary fortification in our country. It is therefore a unique compilation tool with valuable data for the assessment of dietary intakes for the vitamin.

During cortical development, plasticity reflects the dynamic equilibrium between increasing and decreasing functional connectivity subserved by synaptic sprouting and pruning. After adult cortical deafferentation, plasticity seems to be dominated by increased functional connectivity, leading to the classical expansive reorganization from the intact to the deafferented cortex. In contrast, here we show a striking "decrease" in the fast cortical responses to high-intensity forepaw stimulation 1-3 months after complete thoracic spinal cord transection, as evident in both local field potentials and intracellular in vivo recordings. Importantly, this decrease in fast cortical responses co-exists with an "increase" in cortical activation over slower post-stimulus timescales, as measured by an increased forepaw-to-hindpaw propagation of stimulus-triggered cortical up-states, as well as by the enhanced slow sustained depolarization evoked by high-frequency forepaw stimuli in the deafferented hindpaw cortex. This coincidence of diminished fast cortical responses and enhanced slow cortical activation offers a dual perspective of adult cortical plasticity after spinal cord injury.

Folic acid (FA) is an emerging nutritional factor in the pathogenesis of diverse neurodegenerative disorders by still unknown mechanisms. The hippocampus is altered during the loss of cognitive abilities in humans and selectively affected when homocysteine increases. The aim was to evaluate the potential protective role of folic acid in the maintenance of biochemical markers related to the methionine cycle, as well as the integrity of the hippocampus as part of the brain in aged rats. Male Sprague–Dawley rats (18 months old) were assigned to four different folic acid groups (0 mg FA/kg diet, deficient; 2 mg FA/kg diet, control; 8 mg FA/kg diet, moderate supplementation; 40 mg FA/kg diet, extra supplementation) for 30 days. We evaluated several parameters related to the methionine cycle. In addition, hippocampus areas were immunostained for specific neuronal markers and astrocytes. Serum folate levels increased according to FA dietary level (p

Folates and derivatives usually occur as polyglutamates, in different oxidized forms and substitutions in nature. The multiplicity of forms and the generally low content in food makes quantitative analysis of folate a difficult task. A method that uses affinity chromatography followed by ion-pair high performance liquid chromatography was adapted to the analysis of folate distribution in Spanish beers, with simultaneous information on the pteridine ring structure and the glutamate residues. On average, total folate concentration (as sum of individual vitamers expressed in folic acid) in the analyzed beers was 2.0 μg/100 mL. For all the beers, folates were present as monoglutamates and the analysis showed a total absence of polyglutamyl folates. The distribution of the monoglutamyl folate derivatives analyzed in Spanish beers was: 10-formyltetrahydrofolate (41.7% of total folate), tetrahydrofolate (26.5%), 5-methyltetrahydrofolate (17.2%) and folic acid (14.6%). This study provides new information regarding the distribution of naturally occurring folates in beer and contributes to the assessment of folate bioavailability in this beverage.

Folic acid (FA) is a relevant factor in the prevention of a number of pathologies; thus supplementation and/or fortification strategies using FA have been widely introduced as a result. In Spain, there is a lack of reliable data to assess the impact of the increasing number of FA fortified foods. The objective of this work was to evaluate FA fortification levels in breakfast cereal products in Spain. Seventy-three breakfast cereals were analysed for total folate (TF) content. Adequacy was evaluated vs. labelled values (LV), recommended intakes (RI) and tolerable upper intake levels (ULs). Mean TF content ranged from 253 to 427 μg/100 g (76–128 μg/30 g) in different cereal matrix categories. Higher TF content was found in wheat and bran/whole-wheat cereals. As for commercial types, low-fat cereals contained the highest TF levels (445–630 μg/100 g). By consuming these, children (1–9 years old) and women of childbearing age could meet 40–160% and 20–40% of their RIs, respectively, with a standard serving size (30 g). However, children 1–6 years old are at higher risk of excessive FA intake, since low-fat cereals contain more than 50% of their ULs. Our conclusion is that overage (the addition of excess vitamin content) is a practice in FA fortified breakfast cereals. This could be a potential risk for children, but a benefit for women of reproductive age. Physiological status and age are therefore critical factors to take into account to give pertinent advice in consuming FA fortified foods.

Since mandatory folic acid fortification of grains and cereals was introduced in order to prevent neural tube defects, the number of products that are being fortified with folic acid is growing, especially milk and dairy products. However, the effectiveness of this action remains controversial.To investigate the efficiency of skimmed milk as a vehicle for folic acid fortification by the determination of the acute absorption from low-fat fortified milk compared to fortified and unfortified whole milk in healthy subjects.A single-dose bioavailability study was performed using three commercially available milks (whole and skimmed milk fortified with folic acid and unfortified whole milk). Healthy volunteers (3 women, 2 men) were administered a single dose of 430 ml of each milk, at 1-week intervals between test days. Plasma total folate concentrations, at baseline and hourly from 1.5 up to 6.5 h after ingestion, were measured.Plasma folate concentration was significantly increased, when compared to baseline values, 1.5 h after ingestion of skimmed fortified milk, and 2.5 h after whole fortified milk, and remained significantly higher than baseline values for up to 6.5 h after both treatments. The highest plasma folate concentration (20.9 ± 3.1 nmol/l) was obtained 6.5 h postprandial in response to skimmed fortified milk. The acute absorption of folic acid, calculated on the basis of area under the plasma folate concentration curve, was significantly higher from skimmed fortified milk compared to fortified and unfortified whole milk.The absorption of folic acid from fortified skimmed milk is faster than the absorption of folic acid from fortified whole milk, and it renders significantly higher plasma folate concentration when compared to whole milk. These findings indicate that skimmed milk could be considered an efficient food matrix for folic acid fortification.

Spinal cord injury can produce extensive long-term reorganization of the cerebral cortex. Little is known, however, about the sequence of cortical events starting immediately after the lesion. Here we show that a complete thoracic transection of the spinal cord produces immediate functional reorganization in the primary somatosensory cortex of anesthetized rats. Besides the obvious loss of cortical responses to hindpaw stimuli (below the level of the lesion), cortical responses evoked by forepaw stimuli (above the level of the lesion) markedly increase. Importantly, these increased responses correlate with a slower and overall more silent cortical spontaneous activity, representing a switch to a network state of slow-wave activity similar to that observed during slow-wave sleep. The same immediate cortical changes are observed after reversible pharmacological block of spinal cord conduction, but not after sham. We conclude that the deafferentation due to spinal cord injury can immediately (within minutes) change the state of large cortical networks, and that this state change plays a critical role in the early cortical reorganization after spinal cord injury.

Background: Recent studies in animal models have shown that high methionine intakes induce atherosclerotic changes that may be exacerbated when deficiencies of vitamins B6, B12 and folate are present. However, the mechanism underlying this possible atherogenic effect remains unknown. The aim of the present study was to evaluate the effects of methionine on the folate-dependent thymidylate-DNA synthesis, as a possible mechanism of atherogenicity, as well as the effect of high methionine/low folate on several key inflammation markers, such as vascular cell adhesion molecule-1 (VCAM-1), receptor for advanced glycation end products (RAGE) and matrix metalloproteinase-9 (MMP-9) in human aortic endothelial cells. Methods: Deoxyuridine suppression test was performed in order to evaluate thymidylate synthesis. To examine the expression of inflammation markers, cells were exposed to high methionine/low folate media for 9 days. Results: The assayed methionine levels (0.1, 0.5 and 5 mM) did not affect the de novo thymidylate-DNA synthesis. Consistent with this result, methionine (1 and 2.5 mM), alone or in combination with folate deficiency, increased homocysteine levels but did not induce the expression of the inflammation markers evaluated. Conclusion: Under the study conditions, methionine was not able to exert the atherogenic mechanism proposed and did not have the hypothesized inflammatory consequences in human aortic endothelial cells.

BACKGROUND: In intensive agriculture, the use of pesticides and soil fumigants is necessary to produce economically viable crops worldwide. However, this practice may involve undesirable effects on human health and the environment. In 1995, methyl bromide was restricted by the Montreal Protocol because of possible ozone depletion. The objective of this study was to compare intrinsic environmental and toxicological properties of 11 active substances with nematicidal properties, some of them recognized as methyl bromide alternatives. RESULTS: Four groups of active substances were discriminated by a series of principal component analyses (PCAs): (a) high toxicity to non-target fauna, humans and animals and medium persistence in the environment (cadusafos, ethoprophos and fenamiphos); (b) high toxicity to humans, animals and non-target fauna and high persistence (carbofuran and fosthiazate); (c) low toxicity to non-target fauna, humans and animals and low persistence (carbosulfan, benfuracarb and oxamyl); (d) low toxicity to humans, animals and non-target fauna and medium persistence in the environment (1,3-dichloropropene, chloropicrin and methyl bromide). CONCLUSION: Evaluating the multiple aspects of toxicological and environmental properties of active substances through PCA is proposed as a helpful tool for initially comparing the complex toxicological behaviour of active substances as plant protection products. Copyright © 2008 Society of Chemical Industry

10 pages, 3 figures, 4 tables.-- Available online Dec 3, 2007., The effect of high-pressure (HP) treatments on the IgG- and immunoglobulin E (IgE)-binding properties and digestibility of whey proteins was investigated. The formation of protein aggregates was important in whey protein isolate (WPI) and β-lactoglobulin (β-Lg) treated at 200 and 400 MPa at pH 6.8, but was not detected at pH 2.5. Treatment of β-Lg and WPI at 200 and 400 MPa increased binding to β-Lg-specific rabbit IgG and did not affect binding to IgE from allergic patients, but there was no apparent relationship between these responses and the degree of protein aggregation. HP treatment at 400 MPa promoted the hydrolysis of β-Lg by pepsin, but this increased susceptibility of β-Lg to proteolysis was progressively lost during the refrigerated storage of the HP-treated WPI. The higher digestibility of the HP-treated WPI with pepsin did not have an impact on the IgE-binding of the proteolysis products, as compared to non-HP-treated WPI, probably because of the release, in both cases, of specific IgE-binding peptides. Some of these immunoreactive fragments remained after hydrolysis with Corolase PP and probably accounted for a low, but detectable, IgE-binding response., This work was supported by the projects AGL-2004-03322 and AGL-2005-03384 (Ministerio de Educación y Ciencia).

Epidemiological and experimental studies suggest that folate may modulate colorectal carcinogenesis. Its role could be associated with the importance of tetrahydrofolate in DNA and RNA methylation, as well as in thymidylate and purine synthesis, essential for DNA synthesis and repair. In consequence, we analyzed the global DNA methylation and S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) colonic mucosa concentration in biopsies with polyps vs. control biopsies from the same patients ( n =45). Significant colonic DNA global hypomethylation ( p

The design and engineering of hybrid materials exhibiting tailored phononic band gaps are fundamentally relevant to innovative material technologies in areas ranging from acoustics to thermo-optic devices. Phononic hybridization gaps, originating from the anti-crossing between local resonant and propagating modes, have attracted particular interest because of their relative robustness to structural disorder and the associated benefit to ‘manufacturability'. Although hybridization gap materials are well known, their economic fabrication and efficient control of the gap frequency have remained elusive because of the limited property variability and expensive fabrication methodologies. Here we report a new strategy to realize hybridization gap materials by harnessing the ‘anisotropic elasticity' across the particle–polymer interface in densely polymer-tethered colloidal particles. Theoretical and Brillouin scattering analysis confirm both the robustness to disorder and the tunability of the resulting hybridization gap and provide guidelines for the economic synthesis of new materials with deliberately controlled gap position and width frequencies., Hybridization-type band gaps are known to persist in phononic crystals, but their fabrication remains challenging for all-solid hypersonic composites. Here, the authors utilize the elastic anisotropy at the interface of polymer-tethered colloidal particles to control phonon propagation in GHz regime.

Valproate (VPA) is a drug widely used to treat epilepsy, but it has serious adverse effects including hepatotoxicity, teratogenicity and antifolate activity. The mechanism underlying VPA toxicity is unclear although an interaction with folate and other metabolites involved in methionine metabolism has been suggested. The present study was undertaken to evaluate potential changes in the metabolic function of the methionine cycle after acute exposure to a single dose of valproate. Female Wistar rats (n = 30) were treated with 400 mg/kg of VPA. Different groups of six rats were killed at 1 (t1), 3 (t3), 6 (t6), 9 (t9), and 24 (t24) hours after the injection. One group of rats was untreated (n = 6) and was considered the control group. The most pronounced effects of VPA administration were observed 1 h after drug injection. VPA induced a 56% reduction in methionine adenosyltransferase activity and a 54% reduction in plasma vitamin B-6. Increases in the hepatic concentration of S-adenosylhomocysteine and oxidized glutathione, and a reduction in the S-adenosylmethionine/S-adenosylhomocysteine transmethylation ratio also occurred at 1 h. All of these alterations, however, were normalized within 24 h, parallel with a decrease in serum VPA concentration. The acute effects of VPA suggest that the alterations in the methionine cycle could be the common mechanism underlying the hepatotoxic, teratogenic and antifolate effects of the drug.

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

The concept of drug-nutrient interactions is not new, but it has only recently gained currency in medicine. Although the elderly are normally considered to be at particular risk, other groups may also be at risk: infants, adolescents, pregnant women, alcohol and tobacco users, etc. In infants and adolescents there are several factors that may influence the possible interactions: firstly, nutrient needs are usually higher, mainly micronutrients; systems for detoxification of anutrients are not complete; the tendency to restricted diets (especially girls) that are unable to cover the actual recommended intakes for a number of micronutrients (i.e. vitamins); and the dangerous increase in alcohol consumption either in males or females. Administration of drugs in population with adequate vitamin intake is usually not a problem, but administration of drugs in those with borderline intake of vitamins or in patients with low nutritional status can result in symptomatic vitamin deficiency states. The groups at risk of poor vitamin status are smokers (a high proportion of adolescents are active smokers); dieters (skipping meals and dieting to lose weight frequently compromise micronutrient intake, and it should be considered that it is extremely difficult to meet all the requirements at intakes of less than 1,200 calories per day), oral contraceptive users, and pregnant and lactating women, excessive alcohol users, etc. The chapter also focuses on the case of folate: rapidly dividing tissues during the adolescent growth spurt increase requirements for folate. Because of this increased need, folate status appears to be of concern during the age of this rapid growth. A variety of drugs are known to interfere with vitamin utilization by blocking or altering transformation of the vitamin to its metabolically active form. Serum folate levels are known to be low in a high percentage of patients with rheumatoid arthritis, suggesting that aspirin alters the transport of folate by competition for binding sites on serum proteins. Methotrexate, a drug commonly used at low doses for the treatment of psoriasis, rheumatoid arthritis and certain liver disorders, limits the availability of methyl groups derived from one-carbon metabolism by inhibiting competitively a key enzyme in the intracellular folate metabolism. In humans, the antiepileptic drug valproic acid (VPA) is associated with two major adverse effects: teratogenicity and folate deficiency. The mechanisms by which VPA exerts the teratogenic or antifolate effect remain unclear, but an alteration in the methionine cycle is the strongest hypothesis proposed.

En: Food Chemistry. ISSN. 0308-8146. v. 169, (2015) : 283-288 Ready-to-eat foods have nowadays become a significant portion of the diet. Accordingly, nutritional composition of these food categories should be well-known, in particular its folate content. However, there is a broad lack of folate data in food composition tables and databases. A total of 21 fresh-cut vegetable and fruit packed products were analysed for total folate (TF) content using a validated method that relies on the folate-dependent growth of chloramphenicol-resistant Lactobacillus casei subspecies rhamnosus (NCIMB 10463). Mean TF content ranged from 10.0 to 140.9 lg/100 g for the different matrices on a fresh weight basis. Higher TF quantity, 140.9–70.1 lg/100 g, was found in spinach, rocket, watercress, chard and broccoli. Significant differences were observed between available data for fresh vegetables and fruits from food composition tables or databases and the analysed results for fresh-cut packed products. Supplied data support the potential of folate-rich fresh-cut ready-to-eat vegetables to increase folate intake significantly.

Carbon tetrachloride (CCl4) administration to rats produces hepatic cirrhosis and supplementation with S-adenosylmethionine (SAM) can partially prevent CCl4-induced liver injury. These effects are thought to be caused by oxidative stress and the subsequent formation of free radicals, but the mechanism whereby this occurs and the accurate nature of the mechanisms by which SAM exerts its protective action are not well understood. The effect of short-term administration of CCl4 on hepatic DNA methylation and on SAM and S-adenosylhomocysteine (SAH) were assessed. CCl4 administration to rats for 3 weeks resulted in hypomethylation of liver DNA, determined by comparing the extent to which DNA from livers of control or treated animals could be methylated in vitro using [3H-methyl] SAM as methyl donor. This CCl4 effect on DNA methylation was corrected by the administration of SAM (10 mg/kg/d, intramuscularly), with values of methyl groups incorporation comparable with those observed in the control animals. hepatic SAM was decreased by CCl4 (65.3 +/- 5.27 vs. 102.2 +/- 4.89 nmol/g; P < .05) and SAH was increased (69.5 +/- 14.6 vs. 29.4 +/- 3.83 nmol/g; P < .05). This led to a marked reduction of the SAM/SAH ratio (the methylation ratio) from 3.47 in control rats to 0.94 in CCl4-treated animals (P < .05). SAM treatment partially prevented (P < .05) the reduction of the ratio SAM/SAH induced by CCl4. CCl4 also induced a marked elevation of serum homocysteine levels (more than 20-fold; P < .001), which was partially prevented by SAM administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Resumen del póster presentado al 1st International Conference on Food Digestion celebrado en Cesena (Italia) del 19 al 21 de marzo de 2012., Riboflavin binding protein (RfBP) is a minor protein in hen egg, whose potential involvement in egg allergy has seldom been studied. For an allergen to induce a reaction in sensitized individuals, it must survive the passage through the gastrointestinal tract in a sufficiently intact or immunologically active form. The aim of this work was to investigate the capacity of egg white RfBP to bind IgE from egg-allergic patients before and after a simulated gastrointestinal digestion. The protein was cleaved mainly in the gastric phase of digestion. After gastroduodenal digestion, the protein was fragmented but linked through disulfide bonds. The intact protein and its digests were subjected to inhibition ELlSA using sera from patients allergic to egg. The results showed a considerable IgE-binding for intact RfBP, while the digests showed a reduced but still relevant IgEbinding, which varied with the serum used. The digests were then subjected to immunoblot with allergic patients' sera, and at least two IgE-reactive peptides (of apparent molecular weight 3.9 and 5.1 kDa) were detected. These peptides were excised from the gel, tfypsinized and analyzed by MALDI-TOFKOF mass spectrometry for identification. The results showed that peptide 41-84 and 52/53-84 from RfBP could contain one or multiple IgE binding epitopes that would resist gastrointestinal digestion, being large enough to potentially crosslink IgE on mast cells and trigger an allergic reaction in sensitized individuals.

The aim was to investigate whether pregnancy-induced changes in total homocysteine (tHcy) are associated with folate and vitamin B12 nutritional status, genetic C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) enzyme, and gestation outcome at a time when folic acid supplementation started to be recommended in the Spanish health system.In total 154 pregnant women were recruited from among gynecologic patients of the Alcorcón Public Hospital Outpatient Clinic (Madrid, Spain). Blood tests were performed at weeks 15, 24, and 32 of pregnancy. Total Hcy, folate, and vitamin B12 serum fasting concentrations were measured using an IMx system. Genotype analyses were done by polymerase chain reaction/restriction fragment/length polymorphism analysis.Folate and vitamin B12 serum concentrations decreased significantly (P0.01) through pregnancy and reached the lowest values in the third trimester. Serum tHcy concentrations were significantly (P0.01) lower in the second trimester but increased in the third trimester. Frequencies of MTHFR C667T genotype were CC (35.7%), CT (57.2%), and TT (7.1%). Total Hcy concentration was not statistically influenced by maternal genotype. Plasma folate was the single negative predictor of maternal tHcy in the first trimester of pregnancy; 11.1% of gestations resulted in intrauterine growth restriction, 7.9% in gestational diabetes mellitus, and 4.8% in gestational hypertension. No significant differences in serum folate, vitamin B12, or tHcy concentrations were found in complicated pregnancies and these were unrelated to MTHFR genotype.Although tHcy seems to be physiologically low in this Spanish population and unrelated to folate and B12 nutritional status, C677T MTHFR genotype, and some pregnancy complications, we support the statement that appropriate folate concentration may be important throughout pregnancy to prevent abnormalities associated with altered status (e.g., neural tube defects). According to our study, supplementation with folic acid seems to achieve this purpose because diet alone may be insufficient. In addition, a poor vitamin B12 status, as measured by plasma levels, may indicate that supplementation of both vitamins is needed.

7 pages, 4 figures.-- Available online May 18, 2008., This paper examines the potential of high hydrostatic pressure to produce whey protein hydrolysates that combine low immunoglobulin (Ig)G- and IgE-binding with acceptable functional properties, with the aim to produce milk-based ingredients with reduced potential allergenicity that could be used in hypoallergenic foods. Treatment with pepsin and chymotrypsin under high pressure produced, in minutes, hydrolysates in which α-lactalbumin and β-lactoglobulin were totally proteolysed, giving rise to large and hydrophobic peptides. Such hydrolysates presented reduced antigenicity and human IgE-binding properties. The hydrolysates obtained with pepsin at 400 MPa showed improved heat stability, particularly at a pH, close to the isoelectric point of the whey proteins, and their emulsion activity indexes at pH 7.0 were superior to those of the untreated whey proteins. These results suggest that the peptides present retained low antigenicity together with sufficient capacity to form emulsions., This work has been supported by the projects AGL-2004-03322, CONSOLIDER-INGENIO CSD-2007-00063 (Ministerio de Educación y Ciencia, Spain) and S-0505/AGR/0153 (Comunidad Autónoma de Madrid, Spain).

Egg proteins are responsible for one of the most common forms of food allergy, especially in children, and one of the major allergens is ovalbumin (OVA). With the aim to examine the potential of high pressure to enhance the enzymatic hydrolysis of OVA and modify its immunoreactivity, the protein was proteolyzed with pepsin under high-pressure conditions (400 MPa). Characterization of the hydrolysates and peptide identification was performed by reversed-phase high-performance liquid chromatography-tandem mass spectrometry (RP-HPLC-MS/MS). The antigenicity (binding to IgG) and binding to IgE, using the sera of patients with specific IgE to OVA, were also assessed. The results showed that, upon treatment with pepsin at 400 MPa, all of the intact protein was removed in minutes, leading to the production of hydrolysates with lower antigenicity than those produced in hours at atmospheric pressure. However, the exposure of new target residues only partially facilitated the removal of allergenic epitopes, because the hydrolysates retained residual IgG- and IgE-binding properties as a result of the accumulation of large and hydrophobic peptides during the initial stages of hydrolysis. These peptides disappeared at later stages of proteolysis, although reactivity toward IgG and IgE was not completely abolished. Some fragments identified in the hydrolysates (such as Leu124-Phe134, Ile178-Ala187, Leu242-Leu252, Gly251-Ile259, Lys322-Gly343, Phe358-Phe366, and Phe378-Pro385) carried previously identified IgE-binding epitopes. Because some of the peptides found, such as Phe358-Phe366, probably contain only one binding site for IgE, the possibility to use high pressure to tailor hydrolysates that contain mostly peptides with only one IgE-binding site, which may help the immune system to tolerate egg proteins, is suggested.

7 pages.-- PMID: 18680946 [PubMed]., Cows' milk allergy is the most frequent food allergy in children, and β-lactoglobulin (β-Lg) is a major allergen. Milk-based hypoallergenic ingredients are manufactured by enzymatic hydrolysis, a process that could be improved by the application of high-pressure treatments. This study showed that the treatment of β-Lg dissolved in buffer with chymotrypsin and trypsin under high pressure for relatively short times accelerated proteolysis by leading to a rapid removal of the intact protein. The rapid proteolysis of the β-Lg substrate under pressure led to the production, in 20 min, of hydrolysates with lower immunoglobulin (Ig) G binding than those produced in 8 h (chymotrypsin) or 48 h (trypsin) at atmospheric pressure. However, those hydrolysates retained some residual IgE-binding properties that could be traced to the preferential release, during the initial stages of proteolysis, of peptides containing IgE epitopes, such as (Val-41-Lys-60), (Leu-149-Ile-162), and (Ser-21-Arg-40). The formation of these fragments was favored when proteolysis was conducted under high pressure due to the preferential hydrolysis of Arg-40 and Arg-148 by trypsin, and Tyr-42 and Leu-149 by chymotrypsin, all located at the dimer interface of β-Lg or very close to it. Although our results do not support that trypsin and chymotrypsin under high pressure selectively address the allergenic regions of β-Lg, it is possible to select the conditions that quickly produce hydrolysates with reduced potential allergenicity that could be used in hypoallergenic foods.

11 pages.-- PMID: 18292248 [PubMed]., Interpretive summary available at: http://jds.fass.org/cgi/data/91/3/928/DC1/1, This study evaluates the use of high pressure to enhance pepsin hydrolysis of β-lactoglobulin (β-LG). The protein was subjected to high pressure before and during the proteolytic process. Analysis of remnant β-LG, identification of the peptides produced, and evaluation of antigenicity (binding to commercial antibodies) and binding to IgE of allergic patients’ sera were conducted in the hydrolysates. The results showed that the application of high pressure before the enzyme treatment slightly improved the proteolytic process but did not reduce the antigenicity or IgE binding of the hydrolysates. The application of high pressure during the enzymatic treatment enhanced the production of large intermediate fragments that were further proteolysed to smaller fragments as proteolysis proceeded for longer periods. At 400 MPa, all the intact protein was removed in minutes, simultaneously decreasing its antigenicity and serum IgE binding properties. However, for considerable reduction of the antigenicity and IgE binding of β-LG, extending the incubation time with the enzyme was needed to reduce the amount of potentially allergenic intermediate peptides. Changes of β-LG under pressure at acidic pH are discussed.

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

This study reports the influence of colorectal neoplasia on methylation intermediates and folate concentrations in human colonic mucosa, as well as systemic measures of folate status, to examine biomarkers and possible mechanisms of folate-related carcinogenesis. A total of 47 patients were selected from those previously diagnosed with adenocarcinoma of the colorectum undergoing surgery. For each individual, we obtained a biopsy of the adenocarcinoma and a biopsy of normal appearing mucosa, to perform an intra-individual comparison. The ‘methylation’ ratio (S-adenosylmethionine/S-adenosylhomocysteine (SAH)) was lower in pathological tissue vs normal mucosa (P=0.08), mainly due to a much higher SAH concentration (P

There is new evidence that a good folate status may play a critical role in the prevention of neural-tube defects and in lowering elevated homocysteine concentrations. This adequate folate status may be achieved through folic acid dietary supplementation. Folate is a water-soluble vitamin with a low potential toxicity. However, the possible consequences of long-term high-dose folic acid supplementation are unknown, especially those related to the methionine cycle, where folate participates as a substrate. With the aim of evaluating such possible effects, four groups of Wistar rats were classified on the basis of physiological status (virgin v. pregnant) and the experimental diet administered (folic-acid-supplemented, 40 mg/kg diet v. control, 2 mg folic acid/kg diet). Animals were fed on the diets for 3 weeks. Results showed that gestation outcome was adequate in both groups regardless of the dietary supplementation. However, there were reductions (P < 0·001) in body weight and vertex-coccyx length in fetuses from supplemented dams v. control animals. Folic acid administration also induced a higher (P < 0·01) S-adenosylmethionine : S-adenosylhomocysteine value due to increased S-adenosylmethionine synthesis (P < 0·01). However, hepatic DNA methylation and serum methionine concentrations remained unchanged. Serum homocysteine levels were reduced in supplemented dams (P < 0·05). Finally, pregnancy caused lower serum folate, vitamin B6 and vitamin B12 levels (P < 0·05). Folic acid administration prevented the effect of pregnancy and raised folate levels in dams, but did not change levels of vitamins B12 and B6. These new findings are discussed on the basis of potential benefits and risks of dietary folic acid supplementation.

There is new evidence that good folate status may play a critical role in the prevention of neural tube defects and in the maintenance of adequate homocysteine levels, an amino acid recently identified as a risk factor for cardiovascular disease. This has led to different folate recommendations, all of them much higher than the present dietary recommendations. Folic acid is a water-soluble vitamin with a low potential toxicity. However, the possible consequences of long-term, high folate intakes are unknown. Therefore, the present study was undertaken to determine the effects of long-term, high dietary folate supplementation on gestational and nutritional markers in pregnant and virgin rats. Four groups of Wistar rats were classified on the basis of physiological status (virgin or pregnant) and the experimental diets administered (folic acid supplemented, 40 mg/kg diet; or control diet, 2 mg folic acid/kg diet). Rats were fed their respective diets for 3 wk. Two critical periods were used for metabolic balance studies (experimental d 1-5 and 17-21), which involved the determination of fat and protein digestibilities as well as metabolic protein utilization (MPU) and net protein utilization (NPU). Gestational development (number of live fetuses) was adequate in both diet groups regardless of folate supplementation. However, body weight and vertex-coccyx length in fetuses from supplemented dams were less than (P < 0.0001) in fetuses of control dams. Fat and nitrogen digestibilities were not affected by supplementation, but MPU and NPU coefficients were significantly lower (P < 0.05) in the folic acid-supplemented groups, irrespective of physiological status, compared to control rats. These new findings of macro-micronutrient interactions caused by high folate supplementation are discussed on the basis that the vitamin may act as a xenobiotic more than as a nutrient.

[Background/Aim]: The aim of this study was to investigate the effects of S-adenosylmethionine on liver peroxidation and liver fibrogenesis in carbon tetrachloride-induced cirrhosis. [Methods]: Cirrhosis was induced in three groups of six rats by repeated injections of carbon tetrachloride over 9 weeks. One group of animals was treated only with carbon tetrachloride, and the other two received carbon tetrachloride plus S-adenosylmethionine (10 mg/kg intramuscularly daily) from week 3 to week 9, and from week 6 to week 9 of the study, respectively. Two additional groups of six rats, a control group and a group treated only with S-adenosylmethionine, were also studied. Glutathione concentration, thiobarbituric acid-reactive substances, collagen content, prolyl hydroxylase activity, and procollagen type I mRNA expression were determined in liver samples. [Results]: All carbon tetrachloride-treated rats had cirrhosis at the end of the study. Cirrhosis was also present in five of the six carbon tetrachloride-treated rats receiving S-adenosylmethionine for 3 weeks, but in only one of the six rats that received S-adenosylmethionine for 6 weeks. Hepatic glutathione was significantly diminished in carbon tetrachloride-treated rats (2.7 ± 0.3 μmol/g tissue) and returned to normal in rats receiving S-adenosylmethionine for 3 or 6 weeks (3.7 ± 0.13 and 3.9 ± 11 μmol/g tissue, respectively). The hepatic thiobarbituric acid-reactive substances were significantly lower in rats treated with carbon tetrachloride and S-adenosylmethionine for 6 weeks (98 ± 5 nmol/g) than in rats treated with carbon tetrachloride (134 ± 12 nmol/g) and in those treated with carbon tetrachloride and S-adenosylmethionine for 3 weeks (127 ± 13 nmol/g). There were no differences in either hepatic collagen and prolyl hydroxylase activity between rats that received only carbon tetrachloride and those treated with S-adenosylmethionine for 3 weeks. In contrast, carbon tetrachloride-treated rats receiving S-adenosylmethionine for 6 weeks had significantly lower collagen and prolyl hydroxylase activity than the other two groups. A much greater increase in procollagen type I mRNA was found in carbon tetrachloride-treated rats than in rats treated with carbon tetrachloride and S-adenosylmethionine for 6 weeks. Furthermore, there was a significant correlation between the hepatic thiobarbituric acid-reactive substances and prolyl hydroxylase activity and hepatic collagen. [Conclusions]: We conclude that the early administration of S-adenosylmethionine in a model of carbon tetrachloride-induced liver injury restores glutathione levels and reduces lipid peroxidation, resulting in less advanced liver fibrosis., This work was supported in part by grants from Fondo de Investigaciones Sanitarias (FIS 94/0231) and from Europharma (Madrid, Spain).

International audience; In a hypersensitive reaction to pathogen infection, expression of the beta-1,3-glucanase gn1 gene is induced in cells surrounding the necrotic lesions. The 5'-flanking sequence of gn1 was examined to investigate the molecular basis controlling activation of gene expression during this plant defense response. Studies on transgenic tobacco plants containing gn1 promoter deletions fused to the beta-glucuronidase reporter gene revealed the presence of negative and positive regulatory sequences mediating both the level and the spatial distribution of gn1 expression. Promoter sequences to -138 bp were sufficient to confer increased gene expression around the necrotic lesions produced in response to Pseudomonas syringae pv. syringae inoculation. It is demonstrated by electrophoretic mobility shift assays that nuclear proteins in both healthy and hypersensitively reacting tobacco leaves interact with DNA sequences within the regulatory elements identified. Among the binding sequences characterized, the promoter region extending from -250 to -217 bp contained the DNA motif -GGCGGC- found to be conserved in most if not all promoters of genes encoding pathogenesis-related basic proteins. The activity bound by this promoter sequence was stronger in hypersensitively responding tissues than in healthy untreated tobacco leaves.

Background: The antiepileptic drug valproic acid (VPA) may be teratogenic. The mechanism of teratogenicity remains unclear, but it has been hypothesized that VPA interferes with folate metabolism.Objective: To study the effect of VPA on the methionine cycle and transmethylation reactions in pregnant rats.Methods: Wistar rats were treated with VPA (300 mg/kg/day) on gestation days 8, 9, and 10, alone or in combination with folinic acid (FOL, 4 mg/kg/day) on gestation days 8, 9, and 10 or S-adenosylmethionine (SAM, 10 mg/kg/day) throughout gestation days 1 to 10.Results: VPA induced a reduction in maternal methionine serum concentration (p < 0.05) caused by a 24% reduction of methionine synthase activity in liver. This provoked hepatic DNA hypomethylation, although the methylation ratio (S-adenosylmethionine/S-adenosylhomocysteine) was not altered. Homocysteine, folate, and vitamin B12 serum concentrations, as well as methionine adenosyltransferase and betaine homocysteine methyltransferase hepatic activities, did not change. In fetuses exposed to VPA, no effect was observed in hepatic methionine content, but the methylation ratio was reduced (p < 0.01), leading again to hepatic DNA hypomethylation. Coadministration of FOL prevented VPA-induced alterations in methionine synthesis and corrected fetal DNA hypomethylation. By contrast, SAM did not exert a protective effect on fetal DNA methylation.Conclusion: Impaired methionine synthesis and DNA hypomethylation may be involved in VPA-induced teratogenesis.

Historically, food fortification has served as a tool to address population-wide nutrient deficiencies such as rickets by vitamin D fortified milk. This article discusses the different policy strategies to be used today. Mandatory or voluntary fortification and fortified foods, which the consumer needs, also have to comply with nutritional, regulatory, food safety and technical issues. The ‘worldwide map of vitamin fortification’ is analysed, including differences between developed and developing countries. The vitamins, folate and vitamin D, are taken as practical examples in the review of the beneficial effect of different strategies on public health. The importance of the risk-benefit aspect, as well as how to identify the risk groups, and the food vehicles for fortification is discussed. Keywords: food fortification; folic acid; vitamin D; policies; deficiencies (Published: 2 April 2012 )Citation: Food & Nutrition Research 2012. 56 : 5459 - DOI: 10.3402/fnr.v56i0.5459