Tetrahydrobiopterin metabolism in depression and senile dementia of Alzheimer type

Excretion of biopterin and the related pteridines neopterin and pterin was measured in urine samples from a group of 76 male and female unipolar and bipolar depressed outpatients receiving lithium therapy, and compared to 61 male and female control subjects. The ratio of neopterin to biopterin excreted (N/B) was significantly higher in the patients than the controls. The significant positive correlation between urinary neopterin and biopterin shown by the controls was absent in the patients, indicating disrupted biosynthesis of tetrahydrobiopterin.Urinary cortisol excretion in depressed patients was similar to controls, implying normal hypothalmus-pituitary-adrenal axis function in these patients, Serum folate was shown to correlate with urinary total biopterin excretion in female unipolar patients. Two groups of elderly females with senile dementia of Alzheimer type (SDAT) were examined for urinary pteridine excretion. In the first study of 10 patients, the N/B ratio was significantly higher than in 24 controls and the ratio B/B+ N significantly lower. A second study of 30 SDAT patients and 21 controls confirmed these findings. However, neopterin correlated with biopterin in both patients and controls, indicating that the alteration in tetrahydrobiopterin metabolism may be different to that shown in depression. Lithium had no effect in vivo or in vitro on Wistar rat brain or liver biosynthesis of tetrahydrobiopterin at a range of concentrations and duration of dosing period, showing that lithium was not responsible for the lowered biopterin excretion by depressed patients. No significant effects on tetrahydrobiopterin metabolism in the rat were shown by the tricyclic antidepressant imipramine, the anticonvulsant sodium valproate, the vitamin folic acid, the anticatecholaminergic agent amethylparatyrosine, the synthetic corticosteroid dexamethasone, or stimulation of natural cortisol by immobilisation stress. Scopolamine, an ant ichol inergic drug, lowered rat brain pterin which may relate to the tetrahydrobiopterin deficits shown in SDAT.

Oxidative catabolism of tetrahydropterins

Mixed labelled folic acid was administerd to rats. Exposure to N2O was used to give an insight into the major route of scission within the monoglutamate pool, results suggest that THF formed during transport from the gut lumen to the plasma is the major route of scission within the gut. Peroxides in corn oil and arising as a result of lipid peroxidation and autoxidation increase catabolism of the monoglutamate pool and decrease incorporation of administered folates into the polyglutamate pool. It is suggested that peroxides may oxidise B12 resulting in inhibition of methionine synthetase, this results in diminished polyglutamation and increased urinary excretion of 5 CH3THF. Fats undergo peroxidation within tissues, the resulting peroxides increase catabolism of the polyglutamate pool. It is suggested that the NBT assay may reflect polyglutamate breakdown. Antioxidants such as vitamin E (and DES) decrease catabolism of the monoglutamate pool. Administration of DES resulted in changes similar to those observed during malignancy, it is suggested that these changes may precede the onset of tumour development. Vitamin E elevates brain DHPR activity. Since lowered DHPR levels and disturbed THB metabolism have been observed in aging and Down's syndrome it is proposed that vitamin E therapy may prove beneficial in situations where oxidative stress is increased. Brain DHPR activity was increased on administration of peroxides suggesting that in situations of oxidative stress (which may result in increased catabolism of THB) the salvage pathway may be stimulated and loss of THB minimised. N2O exposure had no effect on THB metabolism suggesting that the stimulatory role of 5 CH3THF is due to its role as a methyl donor.

Folate metabolism in the female weanling rat

The metabolism of a mixture of [2-14C] and [3',5',7,9-3H] folic acid was studied in female weanling rats. Intact folates and folate catabolites were excreted in the urine. Folate polyglutamates were found in the tissues. Rats treated with the oestrogen diethylstilbestrol and 17 -ethynyloestradiol exhibited marked changes in the metabolic handling of folic acid and folate catabolism was greatly increased compared to controls. Allopurinol treatment gave greater label retention in the gut, with a substantial increase in catabolism compared to normals. A dose response relationship was illustrated between allopurinol dose and folate catabolism. After lead acetate dosing there was little radioactivity in the urine and tissues over 72h and more radioactivity was retained in the faeces compared to normals. Excretion of intact folates was depressed, especially 5MeTHF and 10CHOTHF. A tenfold increase in both lead and folic acid dosage resulted in an even further decrease of radioactivity in the tissues and urine over 72h. Excretion in the faeces was further elevated. Ferrous sulphate administration resulted in increased catabolism. The retention of radioactivity in the liver, kidney and gut was greatly reduced. A new method of folate analysis; Sephadex LH-20 was introduced. In vitro superoxide anion formation was illustrated using an allopurinol/xanthine oxidase system. Histological studies were employed to qualitatively and quantitatively illustrate the oxidative status in livers and brains of allopurinol and ferrous sulphate dosed rats. Increased dose related formazan deposition was observed when livers of pretreated animals were incubated with nitroblue tetrazolium. Formazan deposition was reduced in pretreated animals also treated with the anti-oxidants vitamin E, mannitol or 4-hydroxy-methyl-4,6-ditertiary-butylphenol. A possible route of folate catabolism is scission by a non-enzymic oxidation involving active oxygen species.

Specific pH‐responsive folate‐conjugate microgels designed for antitumor therapy

Colloidal nanosized folate-conjugated hydrogels for targeted chemotherapy were prepared via a versatile and efficient postsynthetic modification pathway starting from P(NPA-co-NIPAM). The modifications included the introduction of 4-methylpyridine as pH-sensitive pendant groups and the conjugation of folic acid to the microgel network. The microgels showed a specific swelling at pH?

Relationships among dietary intake, dietary patterns, dietary quality and nutrient adequacy and substance use in Latina mother/daughter dyads

This study examined the relationships among dietary intake, substance use, socioeconomic and acculturation-related factors among Latinas in Miami-Dade County. Substance abuse is rising among Latinas. A fuller understanding of this problem is needed given the rise of the Hispanic population and the role of women in Latin society. A better understanding between substance use and dietary intake can guide nutrition interventions to reduce negative substance-related health consequences. A purposeful sample of 320 Latina mother/daughter dyads were recruited and interviewed face-to-face as part of the Latino Women's Study. Dietary intake was collected via a 24-hour recall and examined by (1) nutrient intake, (2) dietary patterns using cluster analysis, (3) quality of diet using the Healthy Eating Index (HEI) and (4) the Dietary Reference Intakes to determine nutrient adequacy. Substance use was measured with the Drug Use Frequency and the Healthy and Daily Living Form. Acculturation was measured with the Cultural Identity Scale. Three dietary patterns emerged based on the number of servings from the food groups established in MyPyramid. None were associated with substance use. Latinas who reported using cannabis, cocaine, sedatives without prescription and/or more than five alcoholic drinks on an occasion at least once a month during the previous twelve months had significantly lower HEI scores (64 vs. 60; F = 7.8, p = .005) and consumed fewer fruits (F = 16, p < .001) than non-users. Latinas classified as mothers whom reported consuming cannabis at least 1-7 times a week had significantly lower HEI scores (F = 4.23, p = .015, η2 = .027) than daughters with the same frequency of substance use. One dimension of acculturation, greater familiarity with Latin culture, was associated with good dietary quality (β = .142, p = .012) regardless of any type of substance used or income level. There was a high prevalence of inadequacy of folic acid intake (50-75%) regardless of substance use. Substance users consumed significantly more energy (1,798 vs. 1,615; p = .027) than non-users. Although effect sizes were small, associations between dietary intake and substance use among Latinas deserve further exploration while acknowledging the combined association with acculturation. ^

Avaliação do pré-natal na atenção primária à saúde no Rio grande do Norte: visão das usuárias

ABSTRACT This study aimed to evaluate the quality of prenatal Primary Care in Rio G rande do Norte, Brazil in 2012 under the program Improving Access and Quality of Primary Care. The study was cross - sectional, quantitative. Included 156 mothers of children under 2 years who received prenatal care at the health evaluated. We applied a ques tionnaire on profile, minimum queries, regularity of attendance, laboratory tests, vaccination, participation in educational activities, guidance received, clinical and obstetric procedures and prescription Ferrous sulphate and folic acid. The descriptive analysis of the criteria used Humanization Program Prenatal and Birth. The results showed that 92% of mothers had six or more visits; 85% with the same care was professional; 94% subsequent appointments scheduled. As for tests and procedures the percentage s were: Urine 98%; HIV - 96%; VDRL and 88%; 91% glucose; tetanus vaccination 93%; educational groups 56% with 36% participation, knowledge of the delivery location and 59% achievement breast exam 65%, 33% and preventive gynecological 43%; 98% supplemented wi th 96% Ferrous Sulfate and Folic Acid. It was concluded that there were advances in Rio Grande do Norte concerning assistance and there are weaknesses in the educational practices and conducting some minimal clinical examinations.

Ethnic differences in grains consumption and their contribution to intake of B-vitamins: results of the Multiethnic Cohort Study

Background: Research indicates that a diet rich in whole grains may reduce the risk of prevalent chronic diseases, including cardiovascular disease, diabetes, and some cancers, and that risk for these diseases varies by ethnicity. The objective of the current study was to identify major dietary sources of grains and describe their contribution to B vitamins in five ethnic groups. Methods. A cross-sectional mail survey was used to collect data from participants in the Multiethnic Cohort Study in Hawaii and Los Angeles County, United States, from 1993 to 1996. Dietary intake data collected using a quantitative food frequency questionnaire was available for 186,916 participants representing five ethnic groups (African American, Latino, Japanese American, Native Hawaiian and Caucasian) aged 45-75 years. The top sources of grain foods were determined, and their contribution to thiamin, riboflavin, niacin, vitamin B6, and folic acid intakes were analyzed. Results: The top source of whole grains was whole wheat/rye bread for all ethnic-sex groups, followed by popcorn and cooked cereals, except for Native Hawaiian men and Japanese Americans, for whom brown/wild rice was the second top source; major contributors of refined grains were white rice and white bread, except for Latinos. Refined grain foods contributed more to grain consumption (27.1-55.6%) than whole grain foods (7.4-30.8%) among all ethnic-sex groups, except African American women. Grain foods made an important contribution to the intakes of thiamin (30.2-45.9%), riboflavin (23.1-29.2%), niacin (27.1-35.8%), vitamin B6 (22.9-27.5%), and folic acid (23.3-27.7%). Conclusions: This is the first study to document consumption of different grain sources and their contribution to B vitamins in five ethnic groups in the U.S. Findings can be used to assess unhealthful food choices, to guide dietary recommendations, and to help reduce risk of chronic diseases in these populations.

Effect of implementation of a preconception counselling resource for women with diabetes: A population based study

Aim To evaluate the effect of regional implementation of a preconception counselling resource into routine diabetes care on pregnancy planning indicators. Methods A preconception counselling DVD was distributed to women by diabetes care teams and general practices. Subsequently, in a prospective population-based study, pregnancy planning indicators were evaluated. The post-DVD cohort (n = 135), including a viewed-DVD subgroup (n = 58), were compared with an historical cohort (pre-DVD, n = 114). Primary outcome was HbA1c at first diabetes-antenatal visit. Secondary outcomes included preconception folic acid consumption, planned pregnancy and HbA1c recorded in the 6 months preconception. Results Mean first visit HbA1c was lower post-DVD vs. pre-DVD: 7.5% vs. 7.8% [58.4 vs. 61.8 mmol/mol]; p = 0.12), although not statistically significant. 53% and 20% of women with type 1 and 2 diabetes, respectively, viewed the DVD. The viewed-DVD subgroup were significantly more likely to have lower first visit HbA1c: 6.9% vs. 7.8% [52.1 vs. 61.8 mmol/mol], P < 0.001; planned pregnancy (88% vs. 59%, P < 0.001); taken folic acid preconception (81% vs. 43%, P = 0.001); and had HbA1c recorded preconception (88% vs. 53%, P < 0.001) than the pre-DVD cohort. Conclusions Implementation of a preconception counselling resource was associated with improved pregnancy planning indicators. Women with type 2 diabetes are difficult to reach. Greater awareness within primary care of the importance of preconception counselling among this population is needed.

Development and application of sensitive genome-wide platforms to study the genetic and epigenetic (DNA methylation) makeup of gametes and early bovine embryos

Pour ce projet, nous avons développé une plateforme pour l’analyse pangénomique de la méthylation de l’ADN chez le bovin qui est compatible avec des échantillons de petites tailles. Cet outil est utilisé pour étudier les caractéristiques génétiques et épigénétiques (méthylation de l’ADN) des gamètes soumis aux procédures de procréation médicalement assisitée et des embryons précoces. Dans un premier temps, une plateforme d’analyse de biopuces spécifiques pour l’étude de la méthylation de l’ADN chez l’espèce bovine a été développée. Cette plateforme a ensuite été optimisée pour produire des analyses pangénomiques de méthylation de l’ADN fiables et reproductibles à partir d’échantillons de très petites tailles telle que les embryons précoces (≥ 10 ng d’ADN a été utilisé, ce qui correspond à 10 blastocystes en expansion). En outre, cet outil a permis d’évaluer de façon simultanée la méthylation de l’ADN et le transcriptome dans le même échantillon, fournissant ainsi une image complète des profils génétiques et épigénétiques (méthylation de l’ADN). Comme preuve de concept, les profils comparatifs de méthylation de l’ADN spermatique et de blastocystes bovins ont été analysés au niveau de l’ensemble du génome. Dans un deuxième temps, grâce à cette plateforme, les profils globaux de méthylation de l’ADN de taureaux jumeaux monozygotes (MZ) ont été analysés. Malgré qu’ils sont génétiquement identiques, les taureaux jumeaux MZ ont des descendants avec des performances différentes. Par conséquent, l’hypothèse que le profil de méthylation de l’ADN spermatique de taureaux jumeaux MZ est différent a été émise. Dans notre étude, des différences significatives entre les jumeaux MZ au niveau des caractéristiques de la semence ainsi que de la méthylation de l’ADN ont été trouvées, chacune pouvant contribuer à l’obtention de performances divergentes incongrues des filles engendrées par ces jumeaux MZ. Dans la troisième partie de ce projet, la même plateforme a été utilisée pour découvrir les impacts d’une supplémentation à forte concentration en donneur de méthyle universel sur les embryons précoces bovins. La supplémentation avec de grandes quantités d’acide folique (AF) a été largement utilisée et recommandée chez les femmes enceintes pour sa capacité bien établie à prévenir les malformations du tube neural chez les enfants. Cependant, plus récemment, plusieurs études ont rapporté des effets indésirables de l’AF utilisé à des concentrations élevées, non seulement sur le développement de l’embryon, mais aussi chez les adultes. Au niveau cellulaire, l’AF entre dans le métabolisme monocarboné, la seule voie de production de S-adénosyl méthionine (SAM), un donneur universel de groupements méthyles pour une grande variété de biomolécules, y compris l’ADN. Par conséquent, pour résoudre cette controverse, une forte dose de SAM a été utilisée pour traiter des embryons produits in vitro chez le bovin. Ceci a non seulement permis d’influencer le phénotype des embryons précoces, mais aussi d’avoir un impact sur le transcriptome et le méthylome de l’ADN. En somme, le projet en cours a permis le développement d’une plateforme d’analyse de la méthylation de l’ADN à l’échelle du génome entier chez le bovin à coût raisonnable et facile à utiliser qui est compatible avec les embryons précoces. De plus, puisque c’est l’une des premières études de ce genre en biologie de la reproduction bovine, ce projet avait trois objectifs qui a donné plusieurs nouveaux résultats, incluant les profils comparatifs de méthylation de l’ADN au niveau : i) blastocystes versus spermatozoïdes ; ii) semence de taureaux jumeaux MZ et iii) embryons précoces traités à de fortes doses de SAM versus des embryons précoces non traités.

La supplémentation nutritionnelle dans la prévention et le traitement des troubles cognitifs associés à la maladie d’Alzheimer

Cette recension systématique analyse 19 essais cliniques randomisés contre placebo qui mesurent l’effet de suppléments d’oméga-3, de vitamines B (B6, B9 et B12), ou de vitamines antioxydantes (C et E), sur le fonctionnement cognitif d’aînés avec ou sans trouble cognitif. Les bases de données consultées pour la recherche des articles sont Cochrane Library, Current Contents, EBSCO, EMBASE, MEDLINE et PsycNet. Les mots clés utilisés sont «alzheimer’s disease», or «mild cognitive impairment», or «cognitive decline»; and «dietary supplements» or «vitamin C», or «vitamin E», or «alpha-tocopherol», or «vitamin B», or «cobalamin», or «folic acid», or «omega 3», or «fatty acids»; and «prevention», or «treatment». La recherche inclut les articles publiés en anglais et en français, de 1999 à juin 2014. Les différents suppléments à l’étude sont bien tolérés et sécuritaires. Des résultats significatifs sont enregistrés sur des mesures cognitives suite à la supplémentation en oméga-3, et en vitamines B, chez des participants sans trouble cognitif ou avec un diagnostic de trouble cognitif léger. Chez les participants atteints de la maladie d’Alzheimer, des résultats significatifs sont surtout enregistrés sur des mesures fonctionnelles, de symptômes psychologiques et comportementaux, ou de qualité de vie, suite à l’administration d’un supplément nutritionnel. La présence d’une hétérogénéité importante dans la méthodologie des essais cliniques limite toutefois les conclusions quant à la pertinence clinique de ces traitements. L’établissement de lignes directrices suite à un consensus d’experts s’avère nécessaire afin d’uniformiser la recherche sur cette nouvelle piste d’intervention dans la prévention et le traitement de la maladie d’Alzheimer.

Primary prevention of neural tube defects: data from the portuguese national registry of congenital anomalies (RENAC)

Background: In Portugal folic acid supplementation is recommended to start at least 2-3 months before conception for primary prevention of Neural Tube Defects. The aim of this study was to evaluate, within gestations with at least one congenital anomaly, possible association between maternal socio-demographic factors and the use of folic acid. Methods: Using data from the Portuguese national registry of congenital anomalies, for the 2004-2013 period, the association between folic acid use during pregnancy and maternal characteristics was studied using the chi-square test. Results: Considering all reported cases with congenital anomaly, the use of folic acid before conception was reported by 12.7% (n = 1233) of the women; 47.8% (n = 4623) started supplementation during the 1st trimester, 7% (n = 680) did not take folic acid and 32.5% (3143) of the records had no information on folic acid use. Women with professions that require higher academic differentiation started the use of supplements before pregnancy (p <0.001); women under 19 years old and with Arab ethnicity (p <0.001) did not take folic acid. Mothers with a previous pregnancy reported less use of folic acid (11.5% versus 14.7%) than mothers without a previous pregnancy (p <0.001). Conclusions: The results suggest some degree of association between maternal characteristics and use of folic acid. To increase the consumption of folic acid before pregnancy new measures are need to promote this primary prevention, among couples and health professionals. This study highlights some maternal characteristics and subgroups of mothers for who the measures should be reinforced.

focus on fruits : 10 tips to help you eat more fruits

Eating fruit provides health benefits. People who eat more vegetables and fruits as part of an overall healthy diet are likely to have a reduced risk of some chronic diseases. Fruits provide nutrients vital for health, such as potassium, dietary fiber, vitamin C, and folate (folic acid). Most fruits are naturally low in fat, sodium, and calories. None have cholesterol. Any fruit or 100% fruit juice counts as a part of the Fruit Group. Fruits may be fresh, canned, frozen, or dried, and may be whole, cut-up, or pureed.

Non-institutionalized nonagenarians health-related quality of life and nutritional status: is there a link between them?

Introduction: Nonagenarian population, clearly increasing, shows different characteristics from the rest of elderly people. Health-related quality of life is a way to study population health in physical, psychological and social dimensions. Objectives: To examine the relationship between nutritional status and health-related quality of life in a group of free-living nonagenarians. Differences with octogenarians were also studied. Methods: Within Villanueva Older Health Study, 20 non-institutionalised people (92.5±3.5 years; 80% women) make the nonagenarian subsample. Nutritional risk was assessed by Mininutritional Assessment questionnaire, dietary intake by a 24-hour dietary recall and health-related quality of life by EuroQoL-5D questionnaire. SPSS was used for statistical analysis. Results: 40% nonagenarians were at risk of malnutrition. Dietary assessment showed magnesium, zinc, potassium, folic acid, vitamin D and vitamin E deficiencies. Problems in mobility were more frequently reported (80%). EQ-5Dindex was associated with MNA (p<0.05). Self-care dimension was associated with calcium and niacin (p<0.05), retinol and cholesterol (p<0.01) intake. Usual activities dimension was associated with niacin (p<0.01) and cholesterol(p<0.05) intake. Pain/discomfort dimension was associated with protein (p<0.01), energy, selenium and niacin (p<0.05) intake. Anxiety/depression was associated with protein(p<0.01) and selenium (p<0.05) intake. Conclusions: Risk of malnutrition is a factor associated to health-related quality of life. Results suggest that energy and some nutrient intakes could be possibly associated to health-related quality of life but further research on this influence is required.

Avaliação nutricional dos idosos institucionalizados no concelho de Viseu

O envelhecimento da população, bem como a alteração da dinâmica da família, têm contribuído diretamente para o aumento do número de idosos institucionalizados. A incidência da desnutrição alcança níveis elevados nestes idosos, sendo essencial o seu diagnóstico precoce para a melhoria da sua qualidade de vida. Constitui objetivo primordial do estudo a avaliação do estado nutricional de idosos institucionalizados no concelho de Viseu, Portugal. A amostra (n=120) é constituída por idosos de ambos os sexos, institucionalizados, com idade igual ou superior a 65 anos, com capacidade para se colocar de pé, sem demência e que não sejam portadores de patologia passível de afetar a digestão, absorção ou utilização dos nutrientes. A avaliação do estado nutricional é determinada tendo em conta parâmetros antropométricos, a aplicação do e Mini Nutricional Assessment (MNA) e dietéticos, através da avaliação da ingestão alimentar (registo de 3 dias). Os questionários aplicados estão validados para a população portuguesa idosa e foram aplicados após consentimento informado. Foram realizadas estatísticas descritivas e inferenciais às diferentes variáveis, de acordo com o género e estratos etários. Considerou-se um nível de confiança de 95%. Dos 120 indivíduos estudados 30% eram do sexo masculino e 70% eram do sexo feminino. As médias das idades eram de 82,36 ± 6,34 anos. A determinação do IMC mostrou que 12,5% dos idosos avaliados exibem baixo peso (IMC 19,6±2,1); 46,7% são eutróficos (IMC 25,7±1,3); 11,7% apresentam excesso de peso (IMC 29,0±0,6), sendo 29,2% classificados como obesos (IMC 33,8±2,9).A avaliação da população pelo MNA evidenciou uma percentagem de desnutrição de 1,7% com uma prevalência de risco de desnutrição (33,3%) mas identifica 65% da amostra como bem nutrida. Os 2 instrumentos utilizados para avaliação do estado nutricional, antropometria (IMC) e MNA mostraram uma correlação estatística entre si positiva. Independentemente do género e do grupo etário verificou-se que o Valor Calórico Total (VCT) ingerido diariamente apresentava valores abaixo do recomendado. Já a ingestão diária de hidratos de carbono e de proteínas apresentou valores médios superiores às recomendações nutricionais enquanto os teores de lípidos ingeridos se situava dentro dos limites recomendados estando porém os valores da ingesta média de fibra total (18g/dia) abaixo dos indicados para a população idosa (25g/dia). Quanto aos micronutrientes encontraram-se deficits de ingestão média diária de minerais e oligoelementos como o cálcio, ferro, magnésio selénio, zinco e iodo e também de algumas vitaminas (D, E, ácido fólico). Conclui-se então que no geral a população estudada apresenta um estado de nutrição normal avaliado através de IMC e do MNA dois instrumentos que estão correlacionados entre si e se complementam. Que a ingestão alimentar apresentada pelos idosos desta amostra é apenas ligeiramente inferior ao recomendado, não colocando em risco o aparecimento de desnutrição. Porém é importante a intervenção dietética no sentido de corrigir determinadas carências (vitaminas, minerais) e prevenir o risco de desnutrição detetado assim como a obesidade.

Impact of the two different iron fortifi ed cookies on treatment of anemia in preschool children in Brazil.

Nutritional intervention in pre-school children using cookies prepared with wheat fl our enriched with iron and folic acid (CWFFeFA) and cookies prepared with cowpea (Vigna unguiculata (L.) Walp) fl our fortifi ed with iron and zinc and wheat fl our enriched with iron and folic acid (CCFFeZn + WFFeFA).