Seleção e aplicação de bactérias láticas produtoras de folato para obtenção de um leite fermentado bioenriquecido e avaliação de biodisponibilidade do folato produzido / Screening and application of folate-producing lactic acid bacteria for production of bioenriched fermented milk and evaluation of the bioavaliability of the produced folate

A deficiência de folato é um problema de saúde pública que vem sendo combatido através da fortificação obrigatória de ácido fólico. Entretanto, a ingestão excessiva pode causar efeitos colaterais indesejados. A forma natural da vitamina produzida por algumas cepas de bactérias láticas pode ser uma alternativa segura para aumentar a ingestão de folato pela população. Este trabalho visou selecionar as melhores cepas de BAL produtoras de folato, identificar as melhores condições para a produção da vitamina e avaliar a biodisponibilidade do folato produzido pelas cepas no leite fermentado, empregando-se testes em modelos animais. O estudo foi desenvolvido com cinco cepas de Streptococcus thermophilus (34v, 170v, 268v, 361v e 341 pc) e um cepa de Lactobacillus plantarum (16cv), todas boas produtoras de folato. As condições de produção e a combinação de cepas que resultaram na melhor produção folato foram utilizadas para produzir um leite biofermentado (BFM), avaliando-se a biodisponibilidade da vitamina produzida empregando-se um modelo animal de depleção/repleção, com camundongos Balb/c submetidos a 14 dias de depleção, seguido de 21 dias de repleção da vitamina. Após os 35 dias, os animais foram sacrificados, retirando-se sangue, rins, fígado, baço e intestino para quantificação de folato e avaliação histológica da mucosa intestinal. Todas as quantificações de folato foram feitas pelo método microbiológico. A melhor combinação de cepas (St. Thermophilus 34v + Lb. Plantarum 16cv) resultou na produção de 300 ng/mL de folato, sendo a temperatura de 42ºC melhor que 37ºC para a produção da vitamina. A produção de folato no leite na fermentação em pH controlado 6,0 foi 35% superior à observada no leite fermentado em pH livre. As concentrações de folato no baço e glóbulos vermelhos foram mais altas nos camundongos que ingeriram leite fermentado bioenriquecido (BFM) em relação aos demais grupos de animais. A relação vilosidade/cripta nos camundongos dos grupos BFM foi igual à observada nos animais que receberam leite suplementado com ácido fólico. Houve aumento da hemoglobina, hematócrito e hemácias nos camundongos que ingeriram BFM, evidenciando a bioeficácia do folato produzido. Esses resultados indicam que a produção de folato por bactérias láticas selecionadas em produtos fermentados pode ser uma boa alternativa para aumentar a ingestão de vitamina B9 pela população

A deficiência de folato é um problema de saúde pública que vem sendo combatido através da fortificação obrigatória de ácido fólico. Entretanto, a ingestão excessiva pode causar efeitos colaterais indesejados. A forma natural da vitamina produzida por algumas cepas de bactérias láticas pode ser uma alternativa segura para aumentar a ingestão de folato pela população. Este trabalho visou selecionar as melhores cepas de BAL produtoras de folato, identificar as melhores condições para a produção da vitamina e avaliar a biodisponibilidade do folato produzido pelas cepas no leite fermentado, empregando-se testes em modelos animais. O estudo foi desenvolvido com cinco cepas de Streptococcus thermophilus (34v, 170v, 268v, 361v e 341 pc) e um cepa de Lactobacillus plantarum (16cv), todas boas produtoras de folato. As condições de produção e a combinação de cepas que resultaram na melhor produção folato foram utilizadas para produzir um leite biofermentado (BFM), avaliando-se a biodisponibilidade da vitamina produzida empregando-se um modelo animal de depleção/repleção, com camundongos Balb/c submetidos a 14 dias de depleção, seguido de 21 dias de repleção da vitamina. Após os 35 dias, os animais foram sacrificados, retirando-se sangue, rins, fígado, baço e intestino para quantificação de folato e avaliação histológica da mucosa intestinal. Todas as quantificações de folato foram feitas pelo método microbiológico. A melhor combinação de cepas (St. Thermophilus 34v + Lb. Plantarum 16cv) resultou na produção de 300 ng/mL de folato, sendo a temperatura de 42ºC melhor que 37ºC para a produção da vitamina. A produção de folato no leite na fermentação em pH controlado 6,0 foi 35% superior à observada no leite fermentado em pH livre. As concentrações de folato no baço e glóbulos vermelhos foram mais altas nos camundongos que ingeriram leite fermentado bioenriquecido (BFM) em relação aos demais grupos de animais. A relação vilosidade/cripta nos camundongos dos grupos BFM foi igual à observada nos animais que receberam leite suplementado com ácido fólico. Houve aumento da hemoglobina, hematócrito e hemácias nos camundongos que ingeriram BFM, evidenciando a bioeficácia do folato produzido. Esses resultados indicam que a produção de folato por bactérias láticas selecionadas em produtos fermentados pode ser uma boa alternativa para aumentar a ingestão de vitamina B9 pela população

Factores de riesgo prenatales y su asociación a malformaciones congénitas en un Hospital Universitario de Referencia / Congenital Malformations: New Challenges For Public Health

Introducción: Las malformaciones congénitas constituyen la segunda causa de mortalidad infantil en América del Sur, según datos de la OMS. Objetivo: Determinar la asociación entre los factores de riesgo prenatales y las malformaciones congénitas de pacientes internados en un hospital de referencia. Material y Método: Estudio retrospectivo, analítico de caso-control, corte transversal en pacientes internados desde Octubre 2014 a Octubre 2015 que cumplieron con criterios de inclusión y exclusión como caso; además en pacientes ambulatorios que cumplieron criterios de inclusión y exclusión como control. Con pareo 1:1 por edad y sexo. Instrumento: encuesta estructurada. Tamaño de muestra con variable cualitativa, valor de Z: 1,9, P: 4% (Porcentaje en población general 2 a 5%) de la variable principal, valor de D: 95% y el valor de p de 0,05, resultando N: 60 por grupo. Resultados: Se consideraron 66 casos y 66 controles pareados por edad y sexo; edades comprendidas de 1 mes a 15 años, media de 2 años (DE: +2,63), masculino 61%. Los Casos provenían 41% (27) del Interior del País y los Controles 11% (7). Las malformaciones más frecuentes fueron las del sistema nervioso central 29% (19/66) seguidas de las cardíacas 23% (15/66). El diagnóstico prenatal por ecografía obstétrica se observó en 33% de los casos (21/66). Al realizar regresión logística multivariada se encontró asociación entre malformaciones congénitas y antecedentes de malformaciones en la familia (OR 20,8, 95% CI 2,66- 162,2), antecedente de un hijo previo con síndrome genético (OR 8,84, 95% CI 1,35- 73,86) y falta de suplementación con ácido fólico antes o durante el embarazo (OR 3,44, 95% CI 1,49- 8,33) distancia de la vivienda de campos fumigados menor a 1 km (OR 3,75, 95% CI 0,98- 14,31) y exposición materna directa a plaguicidas(OR 4,51, 95% CI 1,77- 11,46). Conclusión: La falta de suplemento de ácido fólico, el antecedente de malformación congénita en la familia y la exposición materna a agroquímicos tuvieron asociación estadística significativa. Se plantea probable sesgo de la falta de pareo por Procedencia.

Folic acid and diseases - supplement it or not? / Ácido fólico e doenças - suplementá-lo ou não?

SUMMARY Introduction: folic acid is a water soluble vitamin, which is synthetically-produced and found in fortified foods and supplements. Folate is found naturally in plants, such as the dark green leafy vegetables. Folate is not synthesizedde novo by humans, therefore the daily requirements are met from the dietary intake of folic acid supplements or food rich in this vitamin. Folate deficiency could lead to numerous common health problems. Hyperhomocysteinemia and the possibility of malignancy developments are the long term consequences of this deficit albeit contradictory findings on these claims. Methods: the articles included in this review focused on recent updated evidence-based reports and meta-analyses on the associations of the serum folate/folic acid and the various diseases found globally. Results: the benefit of folic acid supplementation in the pre-conception period for the prevention of neural tube defects (NTDs) was well established and it was suggested that counseling sessions should be given to women with previous pregnancies affected by NTDs. However, supplementation of folic acid and its medicinal effects in the treatment of other diseases were contradictory and unclear. Conclusion: more detailed investigations into the health benefits of folic acid are needed before it could be recommended for supplementation, treatment or prevention of some of the diseases discussed in this review.

RESUMO Introdução: ácido fólico é uma vitamina solúvel em água produzida sinteticamente e encontrada em alimentos e suplementos enriquecidos. O folato é encontrado naturalmente em plantas, como vegetais folhosos verde-escuros. O folato não é sintetizado de novo por seres humanos; portanto, as necessidades diárias são satisfeitas a partir da ingestão de suplementos de ácido fólico ou alimentos ricos nessa vitamina. A deficiência de folato pode levar a inúmeros problemas de saúde comuns. Hiper-homocisteinemia e a possibilidade de desenvolver malignidades são as consequências a longo prazo desse déficit, ainda que os resultados sejam contraditórios sobre essas afirmações. Métodos: os artigos incluídos nesta revisão tratam de relatórios recentes atualizados com base em provas e metanálises sobre a associação entre o folato/ácido fólico e várias doenças encontradas globalmente. Resultados: o benefício da suplementação de ácido fólico no período de pré-concepção para a prevenção de defeitos do tubo neural (DTN) foi bem estabelecido e foi sugerido que sessões de aconselhamento devem ser providas às mulheres com gravidezes anteriores afetadas por DTN. No entanto, os benefícios da suplementação de ácido fólico e os efeitos medicinais no tratamento de outras doenças são contraditórios e pouco claros. Conclusão: investigações mais detalhadas sobre os benefícios do ácido fólico são necessárias antes que a suplementação seja recomendada para tratamento ou prevenção de algumas das doenças discutidas nesta revisão.

Resección de la superficie articular por abordaje dorsal mínimamente invasivo para artrodesis de la articulación interfalángica distal / Joint surface resection with a minimally invasive dorsal approach for arthrodesis of the distal interphalangeal joint

La enfermedad articular degenerativa de la articulación interfalángica distal de los dedos de la mano precede en aparición a todas las demás regiones del cuerpo y genera discapacidad importante. Presentamos el desarrollo de una técnica de artrodesis interfalángica distal asociado con cirugía mínima invasiva. La etiología de los casos fue diversa y nuestro seguimiento promedio fue de 10 meses, todos los casos consolidaron y la recuperación funcional inició desde las dos semanas del postoperatorio. Consideramos que esta técnica puede ser reproducible con resultados satisfactorios en el corto y mediano plazo.

Degenerative joint disease of the distal interphalangeal joint of the fingers precedes its occurrence in all the remaining regions of the body and produces major disability. We describe a distal interphalangeal arthrodesis technique performed with minimally invasive surgery. Case etiology was varied and mean follow-up was 10 months. All cases healed and functional recovery started at postoperative week two. This is a reproducible technique that produces satisfactory results in the short and medium term.

Prevalence and aetiology of anaemia in lymphoid malignancies.

Background. We prospectively studied the prevalence, type and causes of anaemia in newly diagnosed patients with lymphoid malignancies. Methods. Between January 2007 and June 2008, a total of 316 newly diagnosed, consecutive patients (aged 15 years or above) of Hodgkin lymphoma, non-Hodgkin lymphoma and chronic lymphocytic leukaemia with anaemia (haemoglobin <11 g/dl), were analysed to determine the prevalence and a subgroup of 46 patients was analysed for the cause of anaemia. Results. Hodgkin lymphoma, non-Hodgkin lymphoma and chronic lymphocytic leukaemia were the diagnoses in 81 (25.8%), 203 (64.7%) and 30 (9.6%) patients, respectively. Anaemia was present in 134 patients (42.4%). Anaemia of chronic disease was present in 33/46 (71.7%) and iron deficiency in 18/46 (39.1%) patients. Vitamin B12 and/or folate deficiency was detected in 10/46 (21.7%) patients (B12 deficiency alone in 7, folate deficiency alone in 1 and combined B12 and folate deficiency in 2). Autoimmune haemolytic anaemia was detected in 5/46 (10.9%) although direct Coombs test was positive in 17/46 (37%) patients. Among patients with Hodgkin lymphoma and non-Hodgkin lymphoma, anaemia due to bone marrow involvement was present in 16/40 (40%). In most patients with bone marrow involvement, anaemia was due to other causes. In only 3 patients, anaemia was attributable to bone marrow involvement alone. Anaemia was multifactorial in 18/46 (39.1%) patients. Nutritional deficiency alone or in combination was present in 22/46 (47.8%) patients. Conclusion. Anaemia is common in lymphoid malignancies at initial presentation. Besides managing anaemia of chronic disease and bone marrow involvement, nutritional and autoimmune causes should be ruled out.

Poverty, folate deficiency, human immunodeficiency virus and ulcerated vulval sexually transmitted diseases in Jamaica / Pobreza, deficiencia de ácido fólico, virus de la inmunodeficiencia humana, y la ulceratión de la vulva por enfermedades de transmisión sexual, en Jamaica

Sexually transmitted genital ulcerative conditions are declining in Jamaica. The rates at present are far lower than that seen in the 1950s -1960s. Review of the records of the national Comprehensive Clinic has revealed that all of the major sexually transmitted conditions (Syphilis, Lymphogranuloma Venereum (LGV), Chancroid, Granuloma Inguinale and Herpes Simplex) have declined but have had three peaks between 1958 and 2000. Closer review seems to suggest that the peaks were associated firstly with poverty in the 1960s and 1970s and to the HIV epidemic in the 1980s and early 1990s. There are also smaller spikes which appear to be associated with periods of environmental disasters, with a possible association with folate deficiency. This is apparent for the bacterial and chlamydial conditions as well as viral conditions such as Herpes simplex.

Las condiciones ulcerativas genitales transmitidas sexualmente están disminuyendo en Jamaica. En el presente, los índices son muchos más bajos que los observados en la década de 1950 y 1960 respectivamente. La revisión de los archivos de la llamada Nacional Comprehensive Clinic ha revelado que todas las condiciones principales (sífilis, linfogranuloma venéreo, chancroide, granuloma inguinal, y el herpes simple) han disminuido. No obstante, ha habido tres puntos críticos entre 1958 y 2000. Un examen detallado sugiere que estos picos estaban asociados primeramente con la pobreza en los años 60 y 70, y la epidemia de VIH en la década de los 80 ochenta y principios de los 90. Hay también pequeñas alzas que parecen estar asociados con periodos de desastres medioambientales, así como con una posible asociación con la deficiencia de folato. Esto es evidente en el caso de las condiciones bacterianas y clamidiales, así como las condiciones virales tales como la que representa el herpes simple.

Folatos y hierro en mujeres en edad fértil de una comunidad en Venezuela afectada por la incidencia de defectos del tubo neural / Folate and iron in fertile age women from a Venezuelan community affected by incidence of neural tube defects

El objetivo de este estudio transversal fue identificar el estado nutricional de folatos y hierro en mujeres en edad fértil del Municipio Jiménez, Estado Lara, Venezuela. El muestreo fue probabilístico por conglomerados del área urbana y rural, seleccionándose 15 conglomerados donde se estudiaron a las mujeres entre 12 y 45 años (269 mujeres). Previa firma del consentimiento informado, se les practicó: Encuesta con datos personales, antecedentes y variables relacionadas con folatos y hierro; datos socioeconómicos (Encuesta Graffar-Méndez Castellano y Necesidades Básicas Insatisfechas); en muestra de sangre se determinó Hemoglobina y Folato Eritrocitario (FE); en suero se determinó Ferritina, y Folato Sérico (FS). 53,53% de la muestra presentó valores bajos de FS, y el 10,78% valores deficientes. 80,7% presentó deficiencia severa según FE y 5,9% deficiencia moderada. En ambas pruebas, la media fue mayor en mujeres tratadas con Acido Fólico ó embarazadas (p=0,000) y la media del FE también resultó mayor en adultas que adolescentes (p=0,001) y en mujeres no pobres (p=0,011); no hubo diferencias significativas según ingesta de café, alcohol, anticonceptivos, procedencia, estrato social. La anemia se determinó en 11,2%, más frecuente en adultas (p=0,029) y en las del medio urbano (p=0,042). Ferritina baja se encontró en 37.3% de la muestra, las diferencias según variables no fueron significativas. En conclusión, la prevalencia de deficiencia de hierro y folatos en mujeres en edad fértil del Municipio Jiménez es alta, ésta podría constituir un factor condicionante de defectos del tubo neural, por lo cual deben ejecutarse estrategias para superar este déficit.

The objective of this transversal study was to determine folate and iron nutritional status of women in fertile age from Municipio Jiménez, Lara State, Venezuela. The sampling was probabilistic by conglomerates from the urban and rural areas, selecting 15 conglomerates from which women between 12 and 45 years (269), were studied. After signing informed consent, participating were interviewed for personal data, antecedents related to folate and iron, socioeconomic data (Graffar-Mendez Castellano method and unsatisfied basic needs). In blood sample was determined Hemoglobin, and Erythrocytic Folate (FE). Serum was obtained to determine Ferritin and Serum Folate (FS). 53,53% of the sample presented low FS levels, 10.78% were FS deficient. Severe FE deficiency was present in 80.7% of the cases, moderate deficiency affected 5,9%. For both tests, median was higher for women in treatment with Acido Fólico or pregnant (p=0,000), median for FE was higher for adults (p=0.001) and in non poor women (p=0.011). There were no significant differences for coffee, alcohol, anticonceptive consumption, urban or rural resident or socioeconomic strata. The prevalence of anemia was 11,2% being significantly more frequent in adults than in adolescents (p= 0,029) and in urban women (p=0,042). Low ferritin were found in 37,3% of the sample, the effect of different variables was not statistically significant. In conclusion, there is a high prevalence of iron and folate deficiencies in women of fertile age from Municipio Jiménez, which could constitute a conditioning factor for the appearance of neural tube defects.

Síndrome Neuroanémico en el anciano: reporte de un caso / Neuroanemic Syndrome in elder people: report of a case

Se presenta un paciente de 70 años de edad que ingresa por presentar sensación de calambres en miembros inferiores, acompañados de trastornos por inestabilidad de la marcha y que además presentaba cifras bajas de hemoglobinas que al estudiarla resultó ser una anemia megaloblástica. Esta enfermedad es la expresión de un trastorno madurativo de los precursores eritroides y mieloides, que da lugar a una hematopoyesis ineficaz y cuyas causas más frecuentes son el déficit de vitamina B 12 y/o de ácido fólico. La deficiencia de vitamina B12 afecta al sistema nervioso y, aunque sus síntomas son manifiestos (hormigueo en manos y pies, y pérdida de sensibilidad en piernas, pies y manos), muchas veces los ancianos los asocian a la falta de movilidad y al propio envejecimiento, lo que dificulta su identificación a tiempo. En muchas ocasiones, el diagnóstico llega cuando las afectaciones neurológicas y mentales (confusión, depresión y deficiente función intelectual) son evidentes, entonces el deterioro puede ser ya irreversible y desembocar en una demencia y daño axonal irreversible. La relevancia de este caso radica en lo infrecuente de la forma clínica de expresión de esta entidad en nuestro medio.

We present the case of a 70-years-old patient entering our service presenting symptoms of cramps sensation in the lower limbs and disturbances for motion stability, presenting also low values of hemoglobin, resulting in a megaloblastic anemia after a study. This disease is the expression of a maturing disturbance of the erythroid and myeloid precursors, leading to an inefficacious hematopoiesis most frequently caused by vitamin B12 and/or folic acid deficiency. The deficiency of vitamin B12 affects the nervous system, and although its symptoms are clear (crawling in feet and hands), elder people associate them with the proper aging and lack of mobility, making difficult its opportune identification. In many occasions the diagnosis is made when neurological and mental affectations (confusion, depression, and deficient intellectual function) are evident. The deterioration then is irreversible and ended in irreversible dementia and axonal damage. The relevance of this case is based on the infrequentness of the clinical form this entity expresses in our settings.

Oral findings and dental care in a patient with myelomeningocele: case report of a 3-year-old child

Myelomeningocele (MMC) is a congenital malformation of the neural tube that occurs in the first weeks of pregnancy. This malformation refers to the caudal non-closure of the neural tube and neural tissue exposure, which lead to neurological problems, such as hydrocephalus, motor disability, genitourinary tract and skeletal abnormalities and mental retardation. Patients with MMC have an acknowledged predisposition to latex allergy and are usually at a high caries risk and activity due to poor oral hygiene, fermentable carbon hydrate-rich diet and prolonged use of sugar-containing medications. This paper addresses the common oral findings in pediatric patients with MMC, discusses the strategies and precautions to deal with these individuals and reports the dental care to a young child diagnosed with this condition.

Mielomeningocele (MMC) representa uma malformação congênita do tubo neural que acontece nas primeiras semanas de gestação. Esta malformação refere-se ao não fechamento da coluna vertebral expondo a medula espinhal, que levará a problemas neurológicos, como hidrocefalia, dificuldades motoras, anomalias esqueléticas e do trato genito-urinário, além de retardo mental. Pacientes com MMC apresentam uma reconhecida predisposição à alergia ao latex e geralmente apresentam um alto risco e atividade de cárie dental decorrente de uma higiene oral deficiente, de uma dieta rica em carboidratos e do uso prolongado de medicamentos contendo açúcares. Este trabalho discorre sobre os achados bucais em crianças com MMC, discute as estratégias e precauções no manejo destes pacientes e descreve o tratamento odontológico de uma criança diagnosticada com esta condição.

Relación entre los niveles de ácido fólico, vitamina B12 y homocisteína materna y los defectos de tubo neural y labio hendido / Relation between levels of folic acid, vitamin B12 and maternal homocysteine with neural tube defects and cleft lip

El objetivo del trabajo fue determinar la asociación entre los niveles de ácido fólico, vitamina B (Vit B12) y homocisteína (Hci) maternos, con defectos del tubo neural (DTN) y labio hendido (LH) con y sin paladar hendido (c/s PH). Se realizó un estudio tipo casos y controles. Casos, con diagnóstico de DTN y LH c/s PH (n=36) y cuatro controles hospitalarios por caso (n=141). Se incluyeron recién nacidos (RN) y lactantes hasta 12 meses de edad. Las variables de pareamiento fueron: edad del RN o lactante, etnia y hospital. Un 23 por ciento de etnia Tarahumara y 77 por ciento mestizos. Se determinó ácido fólico intraeritrocitario (AFI), plasmático (AFP) y Vit B12 por radioinmunoensayo, la Hci por inmunoensayo de fluorescencia polarizada. Se consideró deficiencia si el AFI fue <160 ng/mL, AFP <3.5 ng/ mL y la Vit B12 <200 pg/mL e hiperhomocisteinemia, si Hci >15 J.mol/L. El análisis estadístico se realizó a través de regresión logística condicionada. Se identificó deficiencia de AFI en el 22 por ciento de las mujeres cuyos recién nacidos o lactantes presentaron algún tipo de defecto congénito y en el 12 por ciento de los controles. La relación entre AFI y DTN, LH c/s PH ajustada por edad materna, exposición a plaguicidas y zona de residencia fue RM 2,96 (IC 95 por ciento 0,92-9,46). No se encontraron diferencias en los niveles de Hci ni de Vit B12. Conclusiones: Nuestros resultados sugieren que RN cuyas madres cursan con una deficiencia de AFI tienen mayor riesgo de presentar DTN y LH c/s PH.

Objective: To determine the association between maternal folate deficiency, neural tube defects (NTDs), and cleft lip, with and without cleft palate (CL/P). Material and methods: A case/control study was conducted. The cases included subjects with diagnoses of NTD and CL/P (n=36) and four hospital controls per case (n=141); the study included newborns (NBs) and nursing babies up to 12monthsof age. The parameter variables were the following: the age of the NB or nursing baby, the ethnic group, and the hospital of origin. The Tarahumara ethnic group made up 23 percent of the cases, while 77 percent were mestizos. The red cell folate (RCF), the plasma folie acid (PFA), and the vitamin B12 levels were determined by radioimmunoassay and the homocysteine levels by polarized fluorescence immunoassay. A deficiency was considered to be present if the RCF were <160 ng/mL, the PFA <3.5 ng/mL and the vitamin B <200 pg/ mL; hyperhomocysteinemia was defined as HC >15 J,mol/L. The statistical analysis was carried out through of conditional logistic regression. Results: An RCF deficiency was identified in 22 percent of the women whose newborn or nursing babies presented with some type of congenital defect and in 12 percent of the controls. The correlation adjusted by maternal age, exposure to pesticides and zone of residence was OR 2.96 (CI 95 percent 0.92-9.46). There was no difference in vitamin B12 or homocysteine levels between groups. Conclusions: Our results suggest that newborns whose mothers present with an RCF deficiency have an increased risk of displaying NTD and CL/P.

Diagnóstico citogenético-molecular del síndrome Xq frágil / Diagnostic testing in fragile X syndrome

El síndrome Xq frágil (SXF) es una causa frecuente de retraso mental (RM); se estima que uno de cada 4.000 varones y una década 6.000 mujeres lo presentan. Clínicamente los individuos afectados se caracterizan por presentar déficit intelectual y cognitivo, déficit de lenguaje, macroorquidismo, fascie alargada y orejas prominentes, entre otras dismorfias faciales. A nivel molecular es posible distinguir fundamentalmente dos tipos de alelos mutados: premutacion y mutación completa, las cuales corresponden a amplificación del trinucleótido CGG localizado en el primer exón del gen FMR1; las premutaciones presentan entre 52 y 200 repetidos y las mutaciones completas sobre 200 CGG, con hipermetilación de la región promotora del gen FMR1 e inhibición de la expresión de la proteína FMRP, causante del RM y dismorfias características de este síndrome. Desde que se identifico la mutación en 1991, la pesquisa de pacientes afectados se inicia por el examen clínico y luego el análisis citogenetico clásico y el test de screening basado en PCR para individuos varones y análisis molecular directo del gen FMR 1 por Southern Blot con la sonda Stb 12.3 para pacientes mujeres; los varones que presentan un PCR alterado deben ser confirmados por Southern Blot. El PCR debe ser usado como método de screening solo en varones con RM, sin historia familiar; es un sensible, rápido, de bajo costo y permite determinar el numero de repetidos CGG. Proponemos el uso conjunto de estos métodos para optimizar el estudio molecular directo del gen FMR1 y establecer un protocolo mas eficiente en la pesquisa de afectados, el estudio de familiares a riesgo y el consejo genético adecuado.

Analytic study of congenital malformations in four hospitals in Baghdad

Congenital malformations are responsible for a considerable proportion of perinatal, neonatal and infant mortality in many Eastern Mediterranean countries. So this study aims to find out the incidence, types and probable risk factors of these malformations in Baghdad. One hundred cases of congenital malformations were studied out of 8090 neonates born in 4 hospitals in Baghdad province over 5 months in 2002 [preterm. term]. The incidence, types and risk factors were analysed. The incidence of congenital malformations was 12.36/ 1000 live births, with the central nervous system malformations being the commonest. There is increased risk in consanguineous marriages 27 [27%], mothers not attending antenatal care 25 [25%], mothers of low gravidity 60 [60%], and mothers not taking folic acid during pregnancy [86.7%]. Consanguineous marriages and mothers not taking folic acid during pregnancy are important risk factors for the occurrence of congenital malformations. So I recommend genetic counseling especially for consanguineous marriages, and giving all pregnant women folic acid before and during pregnancy. A multicentre study will give more broad idea about the incidence, types, and risk factors in our country

Elevated red cell volume in North Indian students.

In a survey for beta-thalassemia carrier status among students in the State of Punjab in India, a surprisingly large number were found to have an elevated red cell volume over 99 fl. The finding was predominantly but not exclusively in females. Similar student surveys from other states showed less macrocytosis. Follow-up tests in a group of affected students were carried out. Volunteers were asked to modify their diet then after six months they were provided with oral vitamin B12. The resulting changes are reported and the implications of the probable vitamin B12 and or folic acid deficiency are considered.

Neural tube defects: pathogenesis and folate metabolism.

Neural tube defects (NTDs) are a group of congenital malformations with worldwide distribution and complex aetio-pathogenesis. Animal studies indicate that there may be four sites of initiation of neural tube closure (NTC). Selective involvement of these sites may lead to defects varying from anencephaly to spina bifida. The NTC involves formation of medial and dorsolateral hinge points, convergent extension and a zipper release process. Proliferation and migration of neuroectodermal cells and its morphological changes brought about by microfilaments and other cytoskeletal proteins mediate NTC. Genetic, nutritional and teratogenic mechanisms have been implicated in the pathogenesis of NTDs. Folate is an important component in one carbon metabolism that provides active moieties for synthesis of nucleic acids and proteins. Several gene defects affecting enzymes and proteins involved in transport and metabolism of folate have been associated with NTDs. It may be possible in future, to identify individuals at higher risk of NTDs by genetic studies. Epidemiological and clinical studies have shown that dietary supplementation or food fortification with folic acid would reduce the incidence of NTDs. The protective effect of folic acid may be by overcoming these metabolic blocks through unidentified mechanisms. Genetic and biochemical studies on foetal cells may supplement currently available prenatal tests to diagnose NTDs. Antiepileptic drugs (AEDs), particularly valproate and carbamazepine have been shown to increase the risk of NTDs by possibly increasing the oxidative stress and deranging the folate metabolism. Accordingly, it is recommended that all women taking AEDs may use 1-5 mg folic acid daily in the pre conception period and through pregnancy.

[Folic acid reduced focal cortical dysplasia of the cerebellum by induction of laminin expression in C57BL/6J mice]

Investigation has shown that folic acid supplementation during the critical period of pregnancy is associated with a decrease in the incidence of skeletal, craniofacial and nervous system malformations; and decreasing folic acid during pregnancy results in a range spectrum of malformations. In this study we used an animal model, which displays focal cortical dysplasia around the secunda fissure of cerebellum. This malformation results from ectopic granule cells which proliferate locally just around the bottom of the secunda fissure. Although there are few studies about the effects of folic acid in prevention the risk of neural tube defects, the objective of the present study was to determine whether folic acid is able to decrease the incidence of focal displasya which possibly results from mutation in gene, Cfp-1 located on chromosome 4. If so, there may be a correlation between consumption of folic acid and laminine expression with reduction of percentage of this malformation. Young female C57BL/6J mice were kept under normal conditions and diet and mated. Next day after mating, finding the vaginal plug was designated as day zero of pregnancy and they were divided in three groups. Experimental group 1 received 0.1 mg/kg folic acid from days 7-10 of gestation; experimental group 2 received the same volume of normal saline on the same days; and the control mice were kept untreated. Each group consisted of 8, 7 and 9 animals respecectively. Pregnant mice from gestational days [E17 to E18] to postnatal days [PD 1 to 5] were sacrificed and collected in formaline-acetic-alcohol or 3.7% paraformaldhyde, serially sectioned and stained with Cresyl violet; and selected sections on PD 1 [the day before formation of malformation] were incubated with monoclonal antibody [anti-laminin]. Our findings showed that the percentage of malformations decreased significantly in experimental group 1 [13.8%] compared to experimental group 2 and controls. The rate of laminin expression in folic acid exposed by special regards to secunda fissure increased significantly. These data provide evidence for the ability of folates and their important roles in preventing mice from central nervous system defects. These data might also have significance for human malformations as well

Malformaciones del sistema nervioso central en el Hospital Clínico de la Universidad de Chile y maternidades chilenas participantes en el estudio colaborativo lationamericano de malformaciones congénitas, ECLAMC / Central nervous system malformations in Chilean hospitals participating in the Latin American collaborative study of congenital malformations, ECLAMC

Background: In Chile, the rates of central nervous system congenital malformations at birth remain high, when compared with the rest of the world. Aim: To report the rates of central nervous system congenital malformations in Chilean hospitals. Material and methods: Using the ECLAMC protocol, every malformed newborn or stillbirth, weighing more than 500 g at birth is registered using a standard protocol, and the next non malformed child of the same sex born in the same hospital is assigned as control. Results: The rates of central nervous system congenital malformations are higher at the University of Chile Clinical Hospital than in the rest of Chilean hospitals or Latin American Hospitals. There are significantly higher rates of anencephalia in Concepcion and spina bifida in Valdivia, Rancagua and Concepcion. In the University of Chile Clinical Hospital, global annual rates have a negative slope of -0.0259 per 1000 born alive, with a correlation coefficient of -0.125 (p <0.05). The slope is positive among children born alive, with an annual rate increase of 0.071. Among stillbirths, the slope is -0.47 per 1000 born alive. Sixty two percent of malformed children were female. Among children with neural tube defects, 30 per cent had a malformed relative and, of these, 66 per cent had the same malformation. Conclusions: Family clustering of neural tube defects, supports the influence of a genetic factor influencing their appearance