Hematological and renoprotective effects of folic acid and lentil extract in diclofenac sodium exposed rats / Efeitos hematológicos e renoprotetores do ácido fólico e do extrato de lentilha em ratos expostos ao diclofenaco de sódio

Excessive intake of non-steroidal anti-inflammatory drugs such as, diclofenac sodium (DS) may lead to toxicity in the rats. In this work, we aimed to examine the protective impact of lentil extract (LE) and folic acid (FA) on the hematological markers, the kidney tissue oxidative stress and the renal function against diclofenac sodium (DS) in male albino rats. The rats (120-150 g) were divided into four equal groups randomly, the first group kept as the untreated control. The second group was administrated with DS (11.6 mg/kg b.wt. orally once/day). The third group was received DS+FA (11.6 mg/kg b.wt.+76.9 microgram/kg b.wt.) orally once/day. The fourth group was treated with DS+LE (11.6 mg/kg b.wt.+500 mg/kg b.wt.) orally once/day. After four weeks, the results revealed that DS produced a significant decrease in the values of red blood cells (RBCs), hemoglobin concentration (Hb), hematocrit (HCT) and white blood cells (WBCs). On the other hand, there was a significant increase in the platelets count. Also, DS induced a renal deterioration; this was evidenced by the significant increase in the serum levels of urea, creatinine, uric acid, Na, Ca, Mg as well as the nitric oxide (NO) level in the kidney tissue. Also, there were a significant reduction in the serum levels of potassium (K) and reduced glutathione (GSH) in the kidney homogenates. Moreover, the findings in the rats treated by DS+LE or DS+FA showed a potential protection on the hematological markers, oxidative stress in the kidney tissue and the renal function disturbed by DS. LE and FA could play a potent role for the prevention the adverse hematological, the kidney tissue oxidative stress and the renal dysfunction caused by DS via their anti-oxidative and bioactive phytochemicals.

A ingestão excessiva de anti-inflamatórios não esteroidais, como o diclofenaco de sódio (DS), pode causar toxicidade em ratos. Neste trabalho, objetivamos examinar o impacto protetor do extrato de lentilha (LE) e ácido fólico (AF) em marcadores hematológicos, no estresse oxidativo do tecido renal e na função renal contra o diclofenaco de sódio (DS) em ratos albinos machos. Os ratos (120-150 g) foram divididos em quatro grupos iguais aleatoriamente, sendo o primeiro grupo mantido como controle não tratado. O segundo grupo foi administrado com DS (11,6 mg / kg de peso corporal por via oral uma vez / dia). O terceiro grupo recebeu DS + FA (76,9 mg / kg de peso corporal por via oral uma vez / dia). O quarto grupo foi tratado com DS + LE (500 mg / kg de peso corporal por via oral uma vez / dia). Após quatro semanas, os resultados revelaram que o DS produziu uma diminuição significativa nos valores de glóbulos vermelhos (RBCs), concentração de hemoglobina (Hb), hematócrito (HCT) e glóbulos brancos (WBCs). Por outro lado, houve um aumento significativo na contagem de plaquetas. Além disso, o DS induziu uma deterioração renal; isso foi evidenciado pelo aumento significativo dos níveis séricos de ureia, creatinina, ácido úrico, Na, Ca, Mg e também do nível de óxido nítrico no tecido renal. Além disso, houve uma redução significativa nos níveis séricos de potássio (K) e glutationa reduzida (GSH) nos homogenatos renais. Além disso, os achados nos ratos tratados com DS + LE ou DS + FA mostraram uma proteção potencial sobre os marcadores hematológicos, estresse oxidativo no tecido renal e função renal perturbada pelo DS. LE e AF podem desempenhar um papel potente na prevenção do estresse hematológico adverso, do estresse oxidativo do tecido renal e da disfunção renal causada pelo DS por meio de seus fitoquímicos antioxidantes e bioativos.

Ácido fólico y embarazo, ¿beneficio o riesgo? / Folic acid and pregnancy, benefit or risk?

RESUMEN El consumo de ácido fólico se ha relacionado con la disminución en la incidencia de malformaciones congénitas y deficiencias obstétricas, pero existen criterios de que no siempre su uso tiene los efectos favorables esperados para la madre y su descendencia. Con el objetivo de estructurar los presupuestos teóricos que sustentan el beneficio y el riesgo del consumo de ácido fólico para el embarazo, se realizó una búsqueda sobre el tema consultándose 37 referencias bibliográficas actualizadas. El ácido fólico ostenta dos grandes funciones en el organismo: la síntesis y reparación de los ácidos nucleicos, así como la síntesis del aminoácido metionina a partir de la homocisteina, esta última, al acumularse en el organismo se asocia a defectos congénitos y enfermedades crónicas del adulto. A partir de estos aspectos se corrobora que su consumo antes y durante el embarazo es beneficioso pues previene defectos del tubo neural, algunas cardiopatías congénitas, hendiduras bucofaciales, síndrome de Down, desórdenes del espectro autista, infecciones obstétricas, preeclampsia, hemorragia uterina, desprendimiento abrupto de la placenta, retardo del crecimiento intrauterino y prematuridad. El consumo excesivo de más de 5 mg/día se ha asociado a anemia por deficiencia de vitamina B12, déficit de zinc, crecimiento intrauterino retardado y prematuridad; en modelos animales acelera la transformación maligna de tumores existentes. Se concluye que el ácido fólico contribuye a preservar una embriogénesis y placentación normal y no se han demostrado efectos adversos por su uso, pero debe ser consumido en la dosis adecuada y por prescripción médica.

ABSTRACT Acid folic intake has been related to the decrease in the incidence of congenital malformations and obstetric deficiencies but there are criteria about folic acid not always achieving the expected favorable results for mothers and their descendants. A search on the theme was carried out with the objective of structuring the theoretical assumptions upholding the benefit and risk of folic acid intake for pregnancy. 37 updated bibliographic references were consulted. The folic acid has two main functions in the organism: nucleic acids´ synthesis and repair, and also the synthesis of the methionine amino acid from homocystein; when the last one accumulates in the organism, it is associated to congenital defects and adults´ chronic diseases. Beginning from these aspects, it is stated that the intake before and after pregnancy is beneficial because it prevents defects of the neural tube, some congenital deficiencies, oral facial clefts, Down syndrome, autism spectrum disorders, obstetric infections, preeclampsia, uterine hemorrhage, sudden placental abruption, intrauterine grow retardation and prematurity. The excessive intake of more than 5 mg/d has been associate to anemia due vitamin B12 deficiency, zinc deficiency, intrauterine retarded grow and prematurity; in animal models it speeds up the malignant transformation of existent tumors. The authors arrived to the conclusion that folic acid contributes to preserving a normal embryogenesis and placentation, and that no adverse effects have been demonstrated, nevertheless it should be taken in adequate doses and for medical prescription.

Impacto del Ácido Fólico en la Incidencia de Fisuras Labiopalatinas de la Población Occidente de la Región Metropolitana, Chile / Impact of Folic Acid on the Incidence of Cleft Lip and Palate of the Western Population of the Metropolitan Region, Chile

RESUMEN: La fisura labiopalatina ha tenido una alta frecuencia en la población chilena. A partir del 2000 se inició el programa de fortificación de la harina con ácido fólico a fin de disminuir los defectos del tubo neural. El objetivo de este estudio fue determinar el impacto que presenta la incorporación del ácido fólico en la incidencia de fisuras labiopalatinas de la población del área occidente de la Región Metropolitana. Se recopiló información a partir de las fichas clínicas de la Fundación Gantz seleccionando a los recién nacidos entre 1990 y 2009, correspondientes a las comunas del Servicio de Salud Occidente de la Región Metropolitana. Desde el 2000 hasta el 2004 se observó una disminución importante en las tasas de fisura labiopalatina, con una tasa de 0,88 fisurados por 1000 recién nacidos vivos. Posteriormente se observó un incremento a partir del 2005 hasta el 2009 llegando a una tasa de 1,52 fisurados por 1000 recién nacidos vivos. En conclusión, el efecto protector del ácido fólico se evidencia en la disminución de las tasas de los recién nacidos con fisuras durante los primeros años de su implementación. Sin embargo, posteriormente se observó un aumento de dichas tasas, lo cual podría deberse al incumplimiento de la norma.

ABSTRACT: Cleft lip and palate has had a high frequency in the Chilean population. From the year 2000 a flour fortification program with folic acid was initiated in order to reduce the defects of the neural tube. The objective of this study was to determine the impact of the incorporation of folic acid in the incidence of cleft lip and palate of the population of the western area of the Metropolitan Region. Information was collected from clinical records of the Gantz Foundation, selecting newborns from 1990 to 2009, corresponding to the districts of the western sector of the Metropolitan Region. From 2000 to 2004 there was a significant decrease in cleft lip and palate rates, with a rate of 0.88 cases per 1000 live births. Subsequently, an increase was observed from 2005 to 2009, reaching a rate of 1.52 cases per 1000 live births. In conclusion, the protective effect of folic acid is evidenced in the reduction of the rates of newborns with cleft palate during the first years of its implementation. However, an increase in these rates was subsequently observed, which could be due to noncompliance with the standard.

Analysis of static and dynamic balance in healthy elderly practitioners of Tai Chi Chuan versus ballroom dancing

OBJECTIVE: To determine whether Tai Chi Chuan or ballroom dancing promotes better performance with respect to postural balance, gait, and postural transfer among elderly people. METHODS: We evaluated 76 elderly individuals who were divided into two groups: the Tai Chi Chuan Group and the Dance Group. The subjects were tested using the NeuroCom Balance Master¯ force platform system with the following protocols: static balance tests (the Modified Clinical Tests of Sensory Interaction on Balance and Unilateral Stance) and dynamic balance tests (the Walk Across Test and Sit-to-stand Transfer Test). RESULTS: In the Modified Clinical Test of Sensory Interaction on Balance, the Tai Chi Chuan Group presented a lower sway velocity on a firm surface with open and closed eyes, as well as on a foam surface with closed eyes. In the Modified Clinical Test of Sensory Interaction on Unilateral Stance, the Tai Chi Chuan Group presented a lower sway velocity with open eyes, whereas the Dance Group presented a lower sway velocity with closed eyes. In the Walk Across Test, the Tai Chi Chuan Group presented faster walking speeds than those of the Dance Group. In the Sit-to-stand Transfer Test, the Tai Chi Chuan Group presented shorter transfer times from the sitting to the standing position, with less sway in the final standing position. CONCLUSION: The elderly individuals who practiced Tai Chi Chuan had better bilateral balance with eyes open on both types of surfaces compared with the Dance Group. The Dance Group had better unilateral postural balance with eyes closed. The Tai Chi Chuan Group had faster walking speeds, shorter transfer times, and better postural balance in the final standing position during the Sit-to-stand Test. .

The prophylactic effects of folic acid and vitamin E against valproic acid during fetal thymus development: an ultrastructural study / Los efectos profilácticos del ácido fólico y la vitamina E contra el ácido valproico durante el desarrollo fetal del timo: un estudio ultraestructural

To evaluate histopathologic differences in the thymus of Wistar Albino rat fetuses prenatally exposed to valproic acid (VPA), folic acid (FA) and vitamin E (Vit-E). VPA (400 mg/kg), FA (400 mcg/kg) and Vit -E (250 mg/kg) were administered to rats on each of gestation days 8, 9 and 10. The fetuses (n:24) were divided into four groups: control, VPA, VPA+Vit-E and VPA+FA groups. On the 20th day of gestation, all pregnant rats were sacrificed and the fetuses were extracted. Thin sections from thymus of live fetuses were stained with uranyl acetate-lead citrate and were examined under transmission electron microscope. The histopathological findings of control group was normal. In VPA group, it showed extensive degenerative changes by VPA were on all tissue compartments when compared to controls. In VPA-FA group, vacuoles, mitochondrial cristalysis and swelling were decreased in cytoplasm. In VPA-Vit-E group, lipid storage and vacuolization were observed. Mitochondrial cristalysis decreased. Our aim in the present study is to analyze histopathological changes which may occur in a high risk experimental model after giving of VPA. In addition, protective roles of the administration of FA and Vit-E are assessed.

Se realizó este estudio para evaluar las diferencias histopatológicas en el timo de fetos de ratas Wistar Albinas expuestas prenatalmente a ácido valproico (VPA), ácido fólico (AF) y vitamina E (Vit-E). VPA (400 mg/kg), FA (400 mcg/kg) y vitamina E (250mg/kg) administradas a ratas en los días 8, 9 y 10 de gestación. Los fetos (n=24) fueron divididos en cuatro grupos: control, APV, APV + vitamina E y VPA + FA. En el día 20 de gestación, todas las ratas preñadas fueron sacrificadas y los fetos fueron extraídos. Se obtuvieron secciones delgadas del timo de los fetos y se tiñeron con citrato de uranilo - acetato de plomo, siendo examinados al microscopio electrónico de transmisión. Los hallazgos histopatológicos del grupo control fueron normales. En el grupo VPA, se observaron cambios degenerativos en todos los compartimentos de tejido en comparación con los controles. En el grupo VPA+FA, las vacuolas, cristalisis mitocondrial e inflamación se redujeron en el citoplasma. En grupo VPA + Vitamina E, se observó el almacenamiento de lípidos y vacuolización. La cristalisis mitocondrial disminuyó. El estudio permitió analizar los cambios histopatológicos que pueden ocurrir en un modelo experimental de alto riesgo después de la administración de VPA, además, las funciones de protección por la administración de AF y vitamina E.

Folate and vitamin B12 intake and risk of squamous-cell carcinoma of the esophagus

Esophageal cancer is one of the most common cancers in Iran and has a high mortality rate. The aim of this study was to assess the association between folate and vitamin B12 intake and risk of squamous-cell carcinoma of the esophagus cancer. In this case-control study, cases [n=47] were patients diagnosed with squamous-cell carcinoma of the esophagus [SCCE] in main hospital Kurdistan and controls [matched with cases by age and sex] were patients with acute non-cancer diseases at the same hospitals [n=96]. Demographic data and physical activity were collected using questionnaires. A semi-quantitative food frequency questionnaire used for nutritional information and folate and vitamin B12 intake were calculated with Nutritionst IV [N4]. Thirty eight percent of cases and 40% of controls were males. Mean age of cases and controls were 58 +/- 18 and 58 +/- 17 years respectively. Mean folate intake among cases was 152.1 microg/day, which was less than in the controls. After adjustment for confounders, folate intake was inversely related with SCCE [OR=0.03, 95% Cl 0.00, 0.12]. The association between vitamin B[12] intake and SCCE was not significant [p=0.46]. Folate intake was inversely related with SCCE: however, there was not a significant association between vitamin 612 intake and SCCE

The Expression of Folate Sensitive Fragile Sites in Patients with Bipolar Disorder

PURPOSE: Genetic factors are known to be important in the etiology of bipolar disorder (BD). The fragile sites (FSs) are a very interesting subject for the study of clinical disorders. The aim of this study was to evaluate fragile sites seen in patients with bipolar disorder and find a correlation between some fragile sites and bipolar disorder. PATIENTS AND METHODS: The frequencies of folate sensitive FSs were compared in short-term whole blood cultures from bipolar patients and from normal individuals. RESULTS: The rate of FS expression in the patients was considerably higher than in the controls (p < 0.001). Several chromosome regions including 1p36, 1q21, 1q32, 3p25, 7q22, 7q32, 11q23, 12q24, 13q32, 14q24, Xp22 and Xq26 were represented considerably more often in the patients than in the controls (p value between 0.001 to 0.036). Among these FSs, the sites 1p36, 1q21, 3p25, 7q22, 7q32, and 14q24 were not observed in other studies. CONCLUSION: These regions can be the most active of hot spots in the genomes of bipolar patients, and may harbor important genes associated with BD.

Expression and identification of folate-sensitive fragile sites in British Suffolk sheep (Ovis aries).

An investigation to understand the dynamics and biological significance of fragile site expression, and identification of 5-fluorodeoxyuridine (FUdR) induced chromosomal gaps/breaks, were carried out in an experimental flock of 45 Suffolk sheep. The statistical comparison revealed, highly significant variation in the frequency of chromosomal fragile site expression between control and FUdR cultures. Mean (+/- S.D.) values for cells with gaps and breaks, or aberrant cell count (AC), and the number of aberrations (NoA) per animal were 2.02 +/- 0.34, 2.42 +/- 0.48, 13.26 +/- 0.85 and 21.87 +/- 1.88 (P lessthan 0.01) in control and FUdR cultures, respectively. The comparison of age revealed nonsignificant variation between control and FUdR cultures. The G-band analysis of fragile site data revealed gaps in 29 autosomal and two X-chromosomal bands in the control cultures, whereas FUdR treated cultures scored 78 unstable bands in autosomes of which 56 were significantly fragile. X-chromosomes expressed breaks and gaps in six G-negative bands and five of them (Xq13, Xq15, Xq17, Xq24 and Xq26) were significantly fragile. The distribution comparison of autosomal fragile sites between sex groups did not reveal any significant variation. Female X-chromosomes were significantly more fragile than the male X-chromosomes. The distribution comparison for age groups (lambs versus adults) revealed significantly higher number of fragile bands in adults. Comparison of published data on reciprocal translocations in sheep with the fragile-site data obtained in this study indicated that the break sites of both phenomena were correlated. Similarities were also found between fragile sites and breakpoints of evolutionary significance in family Bovidae.

Redescubriendo al ácido fólico / Rediscovering the folic acid

La mayor variación del paradigma del soporte nutricional es concebir nutrientes como fármacos y es el caso de los folatos. El folato describe un grupo de compuestos similares química y nutricionalmente esenciales en el metabolismo al actuar como cofactores en reacciones de transferencia de un carbono. Se consideran esenciales, porque el hombre necesita ingerirlos a través de alimentos encontrándose ampliamente extendidos en la naturaleza, en mayor cantidad en las verduras, hígado y cereales. Las funciones de los folatos, referentes a formación de eritrocitos y leucocitos y la prevención de daños en el tubo neural del niño durante la gestación han sido estudiadas. Actualmente es una de las deficiencias nutricionales más comunes en el mundo, y tiene graves consecuencias sobre la salud. La suplementación con ácido fólico ha demostrado ser una medida eficaz en la prevención primaria de dichos defectos si se toma antes de la concepción y durante la primera etapa del embarazo . En los últimos años se identifican funciones relacionadas con malformaciones congénitas, patologías del embarazo, salud cardiovascular y el desarrollo de enfermedad tumoral de los individuos y la enfermedad de Alzheimer. En esta revisión la autora pretende resaltar las funciones de los folatos en la salud humana. En muchos países, incluido el nuestro, la ingestión de folatos es baja, e incluso por debajo de niveles óptimos. Es prioritario aumentar el interés acerca de esta vitamina para aumentar el nivel de folatos, así como explorar las posibilidades de promocionar lo beneficiosas que son para la salud algunas fuentes...

In vitro effect of folic acid and cobalamin [vitamin B12] on adhesion and growth of Giardia lamblia

Giardia lamblia is one of the most common intestinal protozoan parasites infecting human in the world. The goal of this study was searching for in-vitro effect of folic acid and cobalamin on adhesion and growth of G. lamblia as two important mechanisms in the pathogenesis in TYI-S-33 medium. G. lamblia trophozoites were obtained by in- vitro excystation procedure. Three groups of Giardia trophozoites were analyzed: control group, G.lamblia was cultured in TYI-S-33 without any vitamin, 2nd group with 0.1 micro g/ml vitamin B12 or folic acid, and 3rd group with 0.5 micro g/ml of vitamin B12 or folic acid. All culture media tubes incubated at 37 °C. After 2 h of incubation, the adherence into borosilicate culture tubes, and after 24 h the growth of trophozoites were measured .The results showed that in vitamin B12 groups, the growth was increased significantly [P? 0.05] but the adherence decreased significantly [P

Patrón de apoptosis de células blancas de sangre de cordón umbilical (CBSCU) en cultivos in vitro producido por la carbamacepina, Metotrexate y Acido Fólico / Pattern of apoptosis of white cells of blood of umbilical cord (CBSCU) in cultivations in vitro taken place by the carbamacepina, Metotrexate and Folic Acid

Se evaluó el patrón de apoptosis de células blancas de sangre de cordón umbilical producido por la carbamecepina y metotrexate de potencial teratógénico conocido y ácido fólico con efecto protector de defectos de tubo neural, en cultivos in vitro. Se empleó un diseño completamente al azar con 9 repeticiones, el cual responde a un modelo lineal aditivo. Se estudió la acción protectora de ácido fólico en presencia de MTX y CBZ en cultivos in vitro de células blancas de cordón umbilical. Se demopstró que el anticonvulsivante CBZ y el agente anti-inflamatorio MTX inducen apoptosis a 100uM y 50uM respectivamente (dosis terapéutica). En este estudio se encontró que la presencia de ACF (o,1 - 10uM) protege a las células blancas de cordón umbilical contra la inducción de la apoptosis producida por la CBZ y MXT. Por el contrario el ACF no suprime la muerte celular debida al tiempo de cultivo. Entonces el ACF tiene un efecto robusto de protección contra la apoptosis en células blancas de cordón umbilical, esta propiedad provee una nueva vía para el estudio de los mecanismos moleculares y celulares de esta vitamina. Los datos reportados en este estudio son los primeros resultados generados sobre el efecto del MTX, CBZ y ACF y co-cultivos CBZ + ACF, MTX +ACF en cultivos de células blancas de sangre de cordón umbilical humano, demostándose que esta metodología in vitro es capaz de detectar el efecto de agentes protectores y teratogénicos justificándose estudios posteriores de validación de la técnica y evaluación de otros medicamentos para su aplicación.

Evaluation of antimitotic activity of Rotula aquatica (Lour): a traditional herb used in treatment of cancer.

Rotula aquatica was extensively used by vaidyas (Ayurvedic practioners) in holistic treatment of cancer. In the present study, an attempt has been made to evaluate the antimitotic activity of R. aquatica. Preliminary antimitotic screening was done using Allium cepa root tip assay. The mitotic index of the root tips markedly decreased with increasing concentration of the aqueous extract. The different fractions obtained by successive extraction of R. aquatica using solvents of increasing polarity were also evaluated for their antimitotic activity. Tannins were isolated which showed a better activity than the non-tannin fraction. Experiments were also carried out with incorporation of folic acid in the aqueous extract. Folic acid inhibited the antimitotic activity of aqueous extract of R. aquatica in a dose dependent manner. The results obtained were compared with methotrexate--a known drug available in market as anti-cancer agent. The studies were extended to human cells using 3 pancreatic cancer cell lines, viz: HPAF-II, BxPC-3, and CAPAN-2. Extract of R. aquatica was found to be extremely effective in the prevention of cell proliferation of the pancreatic cancer cell lines. The phytochemical evaluation revealed presence of polyphenols (tannins) and steroids. A HPTLC fingerprinting was developed and studied. Two compounds were isolated and subjected to spectral studies like UV, IR and mass spectrums. The empirical formula was derived by considering this data with elemental analysis of the compounds.

Efecto de la administración semanal de ácido fólico sobre los valores sanguíneos / The effect of weekly administration of folic acid on folic acid blood levels

Objetivo. Evaluar el efecto de la administración de 5 mg por semana de ácido fólico sobre los valores sanguíneos. Material y métodos. Estudio de comparación concurrente realizado en zonas urbanas y rurales del estado de Nuevo León, México, en 1998, a 74 mujeres, 39 de ellas con antecedente de un producto con defecto de cierre del tubo neural y 35 sin dicho antecedente. La muestra sólo incluyó a mujeres que parieron durante 1997. Las mujeres recibieron 5 mg de ácido fólico por semana durante tres meses. El AF sanguíneo fue determinado por radioinmunoanálisis (RIA), al inicio y una semana después de la última tableta. Se calcularon promedios y desviaciones estándar. Resultados. El 90 por ciento de las mujeres aumentó significativamente los valores sanguíneos. El ácido fólico intraeritrocitario se incrementó de 150.49 ñ 31.17 ng/ml a 184.21 ñ 35.53 ng/ml (p<0.005) y el plasmático de 5.93 ñ 1.98 ng/ml a 7.03 ñ 2.5 ng/ml (p<0.05). El 82 por ciento alcanzó cifras mayores de 160 ng/ml. Conclusiones. La administración semanal de 5 mg de ácido fólico puede ser una estrategia adecuada y costo eficiente para la suplementación con esta vitamina a la población de escasos recursos. El texto completo en inglés de este artículo está disponible en: http://www.insp.mx/salud/index.html

Neural tube defects: prevention by folic acid and other vitamins.

Folic acid has been demonstrated in clinical trials to reduce significantly the recurrence (and probably occurrence) of neural tube defects (NTD). In the U.K., there has been no decline in prevalence of NTD since the publication of the findings with folic acid. This article examines a series of questions relating to the action of folic acid, with emphasis on the use of mouse models as a source of experimental information which cannot easily be obtained by direct study of humans. Several mouse genetic NTD models exhibit sensitivity to prevention by folic acid, whereas other mice which develop morphologically similar NTD are resistant. Folic acid normalises neurulation in the sensitive mouse strains, providing evidence for a direct effect on the developing embryo, not on the pregnant female: Mouse studies do not support the proposed action of folic acid in encouraging the in utero demise of affected fetuses (i.e. terathanasia). Polymorphic variants of several folate-related enzymes have been shown to influence risk of NTD in humans and an inherited abnormality of folate metabolism has been demonstrated in one mouse NTD model. However, the biochemical basis of the action of folic acid in preventing NTD remains to be determined in detail. NTD in one folate-resistant mouse strain can be prevented by myo-inositol, both in utero and in vitro, raising the possibility of a therapeutic role also in humans. Gene-gene interactions seem likely to underlie the majority of NTD, suggesting that poly-therapy involving folic acid and other agents, such as myo-inositol, may prove more effective in preventing NTD than folic acid treatment alone.

Uso del ácido fólico en la prevención primaria de malformaciones congénitas / Use of folic acid in the primary prevention of abnormalities

Cuando los países mejoran sus condiciones de salud y alcanzan tasas de mortalidad infantil de alrededor de un dígito, las malformaciones congénitas pasan a ocupar el primer lugar entre sus causas. El énfasis en el tratamiento de las malformaciones congénitas debe estar en diseñar estrategias de prevención primaria. Al respecto, durante los últimos años el uso del ácido fólico ha adquirido un rol preponderante. El uso periconcepcional de ácido fólico ha mostrado un claro efecto protector en relación con los defectos de cierre del tubo neural. Considerando la importancia de la prevención primaria en la morbimortalidad a cualquier edad, se ha estimado fundamental planificar estrategias de prevención aplicables en el ámbito individual y poblacional. Se presentan las bases embrionarias, anatómicas, bioquímicas y moleculares de los defectos de cierre del tubo neural y la importancia de iniciar programas a nivel poblacional que aseguren una ingesta suficiente de ácido fólico en las poblaciones objetivo

Prevención primaria de malformaciones congénitas / Primary prevention of congenital malformations

A medida que los países mejoran sus índices de salud, las malformaciones congénitas pasan a ocupar el primer lugar en las causas de mortalidad infantil. El énfasis en el tratamiento de las malformaciones congénitas debe hacerse con buenas estrategias de prevensión primaria. Al respecto, durante los últimos años el uso del ácido fólico ha adquirido un rol preponderante. El uso periconcepcional de ácido fólico ha mostrado un claro efecto protector en relación a algunas malformaciones congénitas frecuentes, especialmente en los defectos de cierre del tubo neural. Considerando la importancia de la prevención primaria en la morbimortalidad a cualquier edad, se ha considerado fundamental planificar estrategias de prevención aplicables en el ámbito individual y poblacional. Se presentan las bases embrionarias, anatómicas, bioquímicas y moleculares de los defectos de cierre del tubo neural y la importancia de iniciar estrategias a nivel poblacional que aseguren una ingesta suficiente de ácido fólico en las poblaciones objetivo