The Evaluation of Folic Acid-Deficient or Folic Acid-Supplemented Diet in the Gestational Phase of Female Rats and in Their Adult Offspring Subjected to an Animal Model of Schizophrenia.

Although folic acid (FA) supplementation is known to influence numerous physiological functions, especially during pregnancy, little is known about its direct effects on the mothers' health. However, this vitamin is essential for the health of the mother and for the normal growth and development of the fetus. Thus, the aim of this study was (1) to evaluate the cognitive effects and biochemical markers produced by the AIN-93 diet (control), the AIN-93 diet supplemented with different doses of FA (5, 10, and 50 mg/kg), and a FA-deficient diet during pregnancy and lactation in female mother rats (dams) and (2) to evaluate the effect of maternal diets on inflammatory parameters in the adult offspring which were subjected to an animal model of schizophrenia (SZ) induced by ketamine (Ket). Our study demonstrated through the Y-maze test that rats subjected to the FA-deficient diet showed significant deficits in spatial memory, while animals supplemented with FA (5 and 10 mg/kg) showed no deficit in spatial memory. Our results also suggest that the rats subjected to the FA-deficient diet had increased levels of carbonylated proteins in the frontal cortex and hippocampus and also increased plasma levels of homocysteine (Hcy). Folate was able to prevent cognitive impairments in the rats supplemented with FA (5 and 10 mg/kg), data which may be attributed to the antioxidant effect of the vitamin. Moreover, FA prevented protein damage and elevations in Hcy levels in the rats subjected to different doses of this vitamin (5, 10, and 50 mg/kg). We verified a significant increase of the anti-inflammatory cytokine (interleukin-4 (IL-4)) and a reduction in the plasma levels of proinflammatory cytokines (interleukin-6 (IL-6)) and TNF-α) in the dams that were subjected to the diets supplemented with FA (5, 10, and 50 mg/kg), showing the possible anti-inflammatory effects of FA during pregnancy and lactation. In general, we also found that in the adult offspring that were subjected to an animal model of SZ, FA had a protective effect in relation to the levels of IL-4, IL-6, and TNF-α, which indicates that the action of FA persisted in the adult offspring, since FA showed a lasting effect on the inflammatory response, which was similar in both the dams and their offspring. In conclusion, the importance of supplementation with FA during pregnancy and lactation should be emphasized, not only for the benefit of the offspring but also for the health of the mother. All this is due to the considerable protective effect of this vitamin against oxidative damage, cognitive impairment, hyperhomocysteinemia, immune function, and also its ability in preventing common processes in post-pregnancy stages, as well as in reducing the risks of neurodevelopmental disorders and enhancing fetal immune development.

[Impact of antiretroviral therapy on occurrences of macrocytosis in patients with HIV/AIDS in Maringá, State of Paraná]. / Impacto do tratamento antirretroviral na ocorrência de macrocitose em pacientes com HIV/AIDS do município de Maringá, Estado do Paraná

INTRODUCTION: AIDS is a disease caused by HIV that compromises the organism's immune system. The advent of highly active antiretroviral therapy (HAART) has promoted substantial improvement in the prognosis for this disease and in HIV/AIDS patients' quality of life. During prolonged treatment, certain hematological disorders are observed, such as anemia and macrocytosis, as well as deficiencies of micronutrient such as vitamin B12 and folic acid. The objective of this study was to correlate the presence of macrocytosis and anemia with HAART use or vitamin B12 and folic acid deficiencies. METHODS: 110 HIV-positive patients were included, in three groups: HAART use with zidovudine (AZT) (group 1), HAART use without AZT (group 2) and no HAART (group 3). RESULTS: None of the patients in any of the three groups presented statistically significant differences relating to hemoglobin level (p = 0.584) or folic acid level (p = 0.956). Group 1 (G1) had a higher mean corpuscular volume (MCV) than G3 (p < 0.05), and group 2 (G2) had a higher volume than group 3 (G3) (p < 0.001). Vitamin B12 levels in G1 and G3 were smaller than those in G2 (p = 0.008). CONCLUSIONS: It was concluded that patients undergoing HAART treatment presented macrocytosis, even though this could not be correlated with the type of HAART or with vitamin B12 deficiency. However, folic acid deficiency was unrelated to either HAART or macrocytosis.

Impacto do tratamento antirretroviral na ocorrência de macrocitose em pacientes com HIV/AIDS do município de Maringá, Estado do Paraná / Impact of antiretroviral therapy on occurrences of macrocytosis in patients with HIV/AIDS in Maringá, State of Paraná

INTRODUÇÃO: AIDS é uma doença causada pelo HIV que compromete o sistema imune do organismo. O advento da terapia antirretroviral (TARV) altamente eficaz promoveu melhora substancial do prognóstico da doença e da qualidade de vida dos pacientes com HIV/AIDS. Durante seu tratamento prolongado, notam-se algumas alterações hematológicas, dentre elas, anemia e macrocitose, bem como carências de micronutrientes, tais como, de vitamina B12 e ácido fólico. O objetivo do presente trabalho é relacionar a macrocitose e anemia ao uso de TARV, ou à deficiência de vitamina B12 ou de ácido fólico. MÉTODOS: Foram avaliados 110 pacientes HIV positivos, comparando-se aqueles em uso de TARV com zidovudina (AZT) (grupo 1), TARV sem AZT (grupo 2) ou sem uso de TARV (grupo 3). RESULTADOS: Os pacientes dos três grupos não apresentaram diferenças estatísticas significativas quanto aos níveis de hemoglobina (p = 0,584) e de ácido fólico (p = 0,956). Os pacientes do grupo 1 (G1) apresentaram volume corpuscular médio (VCM) aumentado quando comparado ao grupo 3 (G3) (p < 0,05), bem como do grupo 2 (G2) em relação ao G3 (p < 0,001). As dosagens de vitamina B12 do G1 e G3 foram menores do que as encontradas pelo G2 (p = 0,008). CONCLUSÕES: Conclui-se que os indivíduos em uso de TARV apresentaram macrocitose, embora não pudesse ser relacionada ao tipo de TARV ou a deficiência de vitamina B12. Entretanto, a deficiência de ácido fólico não esteve relacionada ao uso de TARV e nem à macrocitose.

INTRODUCTION: AIDS is a disease caused by HIV that compromises the organism's immune system. The advent of highly active antiretroviral therapy (HAART) has promoted substantial improvement in the prognosis for this disease and in HIV/AIDS patients' quality of life. During prolonged treatment, certain hematological disorders are observed, such as anemia and macrocytosis, as well as deficiencies of micronutrient such as vitamin B12 and folic acid. The objective of this study was to correlate the presence of macrocytosis and anemia with HAART use or vitamin B12 and folic acid deficiencies. METHODS: 110 HIV-positive patients were included, in three groups: HAART use with zidovudine (AZT) (group 1), HAART use without AZT (group 2) and no HAART (group 3). RESULTS: None of the patients in any of the three groups presented statistically significant differences relating to hemoglobin level (p = 0.584) or folic acid level (p = 0.956). Group 1 (G1) had a higher mean corpuscular volume (MCV) than G3 (p < 0.05), and group 2 (G2) had a higher volume than group 3 (G3) (p < 0.001). Vitamin B12 levels in G1 and G3 were smaller than those in G2 (p = 0.008). CONCLUSIONS: It was concluded that patients undergoing HAART treatment presented macrocytosis, even though this could not be correlated with the type of HAART or with vitamin B12 deficiency. However, folic acid deficiency was unrelated to either HAART or macrocytosis.

Sacarose como veículo de suplementação dietética de ácido fólico em camundongos prenhes / Saccharose as a vehicle for the supplementation of folic acid in pregnant mice

INTRODUÇÃO: A ingestão adequada de folato é essencial durante a embriogênese, e sua deficiência está associada à ocorrência de defeitos no fechamento do tubo neural. OBJETIVO: Determinar se a sacarose é um bom veículo para a suplementação de folato em camundongos. MATERIAL E MÉTODOS: Quarenta camundongos Swiss fêmeas foram divididos nos grupos: C: ração comercial + água ad libitum; DS: ração balanceada isenta de folato + folato adicionado à sacarose diluída na água por 14 dias; D/DS: ração balanceada isenta de folato + água com sacarose sem folato por 14 dias seguida de ração balanceada isenta de folato + folato adicionado à sacarose diluída na água por mais 14 dias; D: ração balanceada isenta de folato + água com sacarose sem folato por 14 dias. Os animais de todos os grupos experimentais receberam ração balanceada isenta de folato + folato adicionado à sacarose diluída na água durante os três dias do acasalamento e nos 15 dias restantes até o sacrifício. RESULTADOS: Os animais dos grupos D e D/DS apresentaram alopecia, palidez ocular e adinamia enquanto consumiam água com sacarose sem folato, sinais que foram revertidos quando receberam folato adicionado à sacarose diluída na água. Não houve diferença entre os grupos em relação a prenhez, implantes, fetos vivos, reabsorção, morte fetal tardia, nível sérico de folato e contagem de hemácias ao final do experimento, não tendo sido observadas anomalias congênitas em nenhum dos grupos. CONCLUSÃO: A sacarose é um meio adequado para a suplementação de folato na dieta.

Adequate folate intake is essential during embryogenesis and its deficiency is associated with neural tube defects. OBJECTIVE: To investigate if saccharose is a good vehicle for the supplementation of folate in mice. MATERIAL AND METHODS: 40 Swiss female mice were allocated into the following groups: C (commercial mouse food + ad libitum water); DS (folate-free balanced diet + saccharose with folate diluted in water for 14 days); D/DS (folate-free balanced diet + folate-free saccharose diluted in water for 14 days, followed by folate-free balanced diet + saccharose with folate diluted in water for 14 days); D (folate-free balanced diet + folate-free saccharose diluted in water for 14 days). Mice from all experimental groups received folate-free balanced diet + saccharose with folate diluted in water during their three-day mating period and thereafter 15 days until animals were put down. RESULTS: Mice from groups D and D/DS showed alopecia, pale eyes and adynamia while on folate-free saccharose water regimen. These symptoms disappeared after the introduction of saccharose with folate diluted in water. No statistical difference was noted among groups as to pregnancy, number of implants, live fetuses, reabsorption, late fetal death, serum folate levels and red blood cells count and no congenital abnormalities were identified in any groups by the end of the experiment. CONCLUSION: Saccharose is a suitable vehicle for the dietary supplementation of folate.

[Decrease of folic acid and cognitive alterations in patients with epilepsy treated with phenytoin or carbamazepine, pilot study]. / Disminución de ácido fólico y alteraciones cognitivas en pacientes con epilepsia tratados con fenitoína o carbamazepina, estudio piloto.

INTRODUCTION: Phenytoin and carbamazepine were the antiepileptic drugs most frequently used in Mexico and throughout the world. Epileptic patients who take these drugs have a variety of collateral effects including the decrease of folates plasmatic level. Low seric folic acid concentration has been associated with a decline in cognitive functions. The administration of a combined treatment with folic acid could ameliorate these difficulties. OBJECTIVE: To describe the effect of the folic acid in the cognitive function in epileptic patients who take phenytoin and carbamazepine. METHODS: We chose patient who have epilepsy and that are being treated with phenytoin, carbamazepine or both and formed two groups. The study group was treated with a daily dose of 5 mg of folic acid and the control group was administered placebo for a period of six months, with nine patients in each group of same age, sex, education level, epilepsy's evolution, frequency of seizures, EEG abnormalities and antiepileptic drugs plasma levels. We registered data at the beginning (basal) and at the end of the study. RESULTS: Measurements of basal folic acid plasma levels in both groups were under the referential value. The neuropsychological assessment at the beginning (Mini-Barcelona test) showed a deficit in the verbal memory skills in both groups. After six months of treatment with folic acid (study group), the folic acid plasma level was 12.2 mg/mL (p < 0.01) higher than the basal value. Verbal memory test has improved with respect to the basal value (p < 0.05). The numbers of seizures and the plasma levels of the antiepileptic drugs remained unchanged. On the other hand, the group treated with placebo did not improve. CONCLUSION: Treatment with folic acid is safe and without side effects, it improved the cognitive function in patients with epilepsy treated with phenytoin and carbamazepine.

Disminución de ácido fólico y alteraciones cognitivas en pacientes con epilepsia tratados con fenitoína o carbamazepina, estudio piloto / Decrease of folic acid and cognitive alterations in patients with epilepsy treated with phenytoin or cartnabazepine, pilot study

Introduction. Phenytoin and carbamazepine were the antiepileptic drugs most frequently used in Mexico and throughout the world. Epileptic patients who take these drugs have a variety of collateral effects including the decrease of Mates plas-matic level. Low serie folie acid concentration has been associated with a decline in cognitive functions. The administration of a combined treatment with folie acid could ameliorate these difficulties. Objective.To describe the effect of the folie acid in the cognitive function in epileptic patients who take phenytoin and carbamazepine. Methods. We chose patient who have epilepsy and that are being treated with phenytoin, carbamazepine or both and formed two groups. The study group was treated with a daily dose of 5 mg of folie acid and the control group was administered placebo for a period of six months, with nine patients in each group of same age, sex, education level, epilepsy's evolution, frequency of seizures, EEG abnormalities and antiepileptic drugs plasma levels. We registered data at the beginning (basal) and at the end of the study. Results.Measurements of basal folie acid plasma levels in both groups were under the referential value. The neuropsychological assessment at the beginning (Mini-Barcelona test) showed a deficit in the verbal memory skills in both groups. After six months of treatment with folie acid (study group), the folie acid plasma level was 12.2 mg/mL (p < 0.01) higher than the basal value. Verbal memory test has improved with respect to the basal value (p < 0.05). The numbers of seizures and the plasma levels of the antiepileptic drugs remained unchanged. On the other hand, the group treated with placebo did not improve. Conclusion.Treatment with folie acid is safe and without side effects, it improved the cognitive function in patients with epilepsy treated with phenytoin and carbamazepine.

Introducción. La difenilhidantoína (DFH) y la carbamazepina (CBZ) son los antiepilépticos más empleados en México y en el mundo, los pacientes con epilepsia que emplean estos fármacos presentan una disminución en las concentraciones séricas de ácido fólico, una de las causas que pueden contribuir a un deterioro cognitivo, por lo que la terapia sustitutiva con ácido fólico pudiera mejorar estas alteraciones. Objetivo. Describir el efecto de la disminución del ácido fólico en la cognición de pacientes con epilepsia tratados con difenilhidantoína y carbamazepina. Material y métodos. Incluimos pacientes tratados con carbamazepina, fenitoína o ambos, con epilepsia. Formamos dos grupos: Un grupo experimental recibió ácido fólico 5 mg/día y otro grupo control recibió placebo durante seis meses, nueve pacientes en cada grupo; pareados en la edad, sexo, escolaridad, tiempo de evolución, námero de crisis, alteraciones EEG, niveles séricos de anticonvulsivos, realizamos estudios neuropsicológicos al inicio (básales) y al final del estudio a ambos grupos. Resultados. Las básales del ácido fólico en ambos grupos estuvieron por debajo del valor de referencias. En las pruebas neuropsicológicas (básales) (prueba de Mini-Barcelona) se halló un déficit en el área de la memoria verbal en ambos grupos. Después de seis meses de tratamiento con ácido fólico (grupo experimental) los niveles de ácido fólico alcanzaron 12.2 ng/mL (p < 0.01) con respecto a su basal; las pruebas de memoria verbal mejoraron con respecto a su basal (p < 0.05); el námero de crisis y los niveles séricos de los anticonvulsivos no se modificaron. El grupo con placebo no presentó ninguna mejoría. Conclusiones. El tratamiento coadyuvante con ácido fólico es seguro, libre de efectos adversos y mejoró las alteraciones cognitivas (memoria verbal) de estos pacientes.

Effects of taurine deficiency and chronic methanol administration on rat retina, optic nerve and brain amino acids and monoamines.

A chronic methanol (MeOH) intoxication scheme (2 g/kg/day ip for 2 weeks) was carried out in Sprague-Dawley rats, previously depleted of folates with methotrexate (MTX). beta-Alanine (beta-Ala), 5%, was also administered to some animals in the drinking water. Amino acids were determined in plasma, retina, optic nerve, hippocampus and posterior cortex by HPLC with fluorescence detection and monoamines in retina, hippocampus and posterior cortex by electrochemical detection. Beta-Ala administration reduced taurine (Tau) levels in plasma, hippocampus and posterior cortex, but not in retina and optic nerve. Aspartate (Asp) concentration in the optic nerve was increased in MTX-MeOH treated animals, and the administration of beta-Ala did not modify this elevation. The association of beta-Ala with MTX-MeOH produced an increase of threonine, and a decrease of 5-hydroxytryptamine (5-HT) in the retina without modifying 5-hydroxyindoleacetic acid, whereas in the hippocampus an elevation of asparagine was observed. We conclude that, in the retina, beta-Ala in combination with MTX-MeOH increased serotonin and decreased dopamine (DA) turnover rate, and resulted in changes in the amino acid balance, that could affect glycinergic activity. On the other hand, in the hippocampus, Asp metabolism could be affected by Tau depletion with beta-Ala.

Deficiencia de acido fólico durante el tratamiento de las artritis reumatoide con metotrexate / Folic acid deficiency of rheumatoid arthritis patients receiving methotrexate

Para determinar el estado del Acido Fólico (AC F) los pacientes con Artritis Reumatoide (AR) que reciben Metotrexate (MTX) se realizó un estudio prospectivo transversal multicéntrico, comparando pacientes con AR que usaban MTX con los que no lo usaban. Se encontró disminución del Acido Fólico Intraeritrocitario (AFI) en el grupo tratado con mayor o menos 7.5 mg/sem de MTX, no se encontró relación entre el nivel de AFI y el tiempo de tratamiento con MTX o el uso concomitante de Antiinflamatorios no Esteroideos (AINES). La repercusión de la disminución del AFI en los parámetros hematológicos fue el aumento del Volumen Corpuscular Medio (VCM) y de la Hemoglobina Corpuscular Media (HCM), no se encontró influencia de esta disminución en la anemia de los pacientes, tampoco en las cifras de leucocitos, plaquetas y reticulocitos. Se encontró correlación entre el AFI y el Acido Fólico Sérico en los pacientes que recibieron MTX no así en el grupo control

Hematologic abnormalities in adolescents who take oral contraceptive pills.

PIP: Sexually active patients (12 to 19 years of age) participated in a study designed to determine if adolescents who take oral contraceptives are susceptible to hematologic abnormalities. This involved individual medical histories recording vitamin ingestin, alcohol consumption, type of contraceptive used, duration of usage and menstrual cycle. Blood samples were drawn for determinations of serum folate, B12, ferritin, blood count and polymorphonuclear leukocyte lobe count. Results indicate that adolescents with nutritionally poor diets are potentially high risks for developing folic acid deficiency while taking oral contraceptives. The data indicate no significant differences in the mean hemoglobin, red blood cell indices or polylobe count in either the patient or control group. The authors stress a need to gather more data on the effects of long term contraceptive pill usage. It is concluded that although contraceptive pill use appears to increase the risk of developing cellular folate deficiency, especially in white women, the pill appears to offer some protection against iron deficiency and is not associated with anemia.^ieng