Chronic Folic Acid Deficiency Research Articles

Analysis of genome instability biomarkers in children with non-syndromic orofacial clefts.

The non-syndromic cleft lip and/or palate (NSCL/P) is a common birth defect caused by a combination of genetic and environmental factors. The possible role of genome instability on NSCL/P patient needs more investigation, since DNA metabolism is an essential cellular function to keep cells with normal genotypes and gene expression patterns according to tissue specificities, which is critical during embryo development because it requires sensitive regulation of cell proliferation, apoptosis and differentiation. Thus, genome stability is ultimately essential to maintain a healthy life. The aim of this study was to assess the frequency of genome instability biomarkers and their relationship with NSCL/P. Cytokinesis-block micronucleus assay was performed to estimate the biomarkers frequency and gene expression was analyzed by the transcriptogram in order to further explore the role of genome instability and other biological processes in this birth defect. The NSCL/P patients had higher baseline frequency of micronucleus, nuclear buds and nucleoplasmic bridges (P < 0.001) than the control group. Moreover, new nuclear morphologies (fused, circular and horseshoe) was detected in the patients' cells analyzed, possibly indicating that chronic folic acid deficiency is interfering in their genome instability. Children with clefts had 2.3 times more risk to have high micronuclei frequency (P = 0.043) according to binary logistic regression. The high genomic instability in children with oral clefts suggests that misrepaired double strand breaks in DNA that create micronuclei representing a significant factor in NSCL/P development. This study was published in 52nd EUROTOX Abstract Book.

Stress Induced Platelet Dysfunction in Rats with Folic Acid-Deficient Hyperhomocysteinemia

A rat model of experimental hyperhomocysteinemia (HHC) caused by chronic folic acid deficiency was used to study the impact of swimming stress on the values of agonist-induced platelet aggregation and ATP release. At week 8 of HHC development, platelet aggregability and ATP levels in response to test inductors (ADP, thrombin, and collagen) moderately increased. After stress, the rate of platelet aggregation showed a more increase in rats with HHC; however, the increment was less pronounced than in the control group. The similar changes was observed in ATP, the release of which from dense platelet granules decreased in the experimental animals exposed to stress changes as compared to the controls. The experimental findings suggest that the stress potentiates platelet dysfunction in HHC.

The long-term sequelae of ileocolic anastomosis in childhood: A retrospective survey

The long-term effects of ileocolic anastomosis in children are not known. We therefore carried out a survey of all such patients treated at our hospital between 1971 and 1985. Thirty-seven patients were identified and invited to attend for follow-up. Twenty-seven (73 per cent) were examined and included in the survey. Mean age at survey was 7.8 years (range 1.6-17.6 years) and mean duration since operation was 6.3 years. Necrotizing enterocolitis and intussusception were the commonest indications for operation. As judged by height, weight and skin fold thickness, all patients were well nourished. Seven (26 per cent) had loose stools, five had chronic folic acid deficiency and one was vitamin B12 deficient. We conclude that resection of the ileocaecal region is well tolerated in childhood and does not affect growth. Loose stools are directly related to the length of ileal resection.

Celiac disease, cerebral calcifications and epilepsy syndrome

The syndrome of coeliac disease, epilepsy and cerebral calcifications is a rare complication of coeliac disease. The pathological changes consist in a patchy pial angiomatosis and resemble those of Sturge-Weber syndrome, whose variant without port-wine angioma must be ruled out. Typical course includes three stages leading to a severe encephalopathy. However, the mental impairment is extremely variable. The pathogenetic process is so for unknown; main clues involve a chronic folic acid deficiency or a HLA-related autoimmune disorder. Treatment requires early gluten-free diet and anti-epileptic drug.

Folate Deficiency in Rats Fed Amino Acid Diets

Growth rate, hematological changes, serum, erythrocyte and liver folate levels, and urinary excretion of formiminoglutamic acid (FIGLU) were measured in rats fed p-aminobenzoic acid (PABA)-free, sulfonamide-supplemented purified amino acid diets with and without folic acid and fiber, individually and in combination. Fiber had no effect on growth but was necessary to prevent mortality in the absence of folic acid. Folic acid did not affect growth during the first 40 days, but after this period rats failed to gain weight in the absence of folic acid. Although blood hematocrit was lower when the diet was devoid of fiber and folic acid and leucocyte counts were lower when the diets were devoid of folic acid, the hematological values remained within normal physiological limits for healthy rats of comparable age. FIGLU excretion was increased and serum, erythrocyte and liver folate levels were depressed when rats were fed folic acid-free diets for 28 days. Neutrophil hypersegmentation was clearly evident after 28 days of feeding the folic acid-free diets. The use of an amino acid diet without PABA but containing 5% fiber and 1% succinylsulfathiazole is a useful system to study chronic folic acid deficiency in the rat.

Therapeutic activity of xanthopterin added to p-aminobenzoylglutamic acid in experimental macrocytic anemia of rat.

Conclusions(1) Chronic folic acid deficiency was induced in rats with a highly purified diet containing 1% streptomycin. (2) Xanthopterin causes a small increase in the number of erythrocytes but does not alter the color index or leukopenia. (3) P-aminobenzoylglutamic acid has no effect on the hematological picture resulting from a chronic deficiency of folic acid in the rat. (4) The simultaneous parenteral administration of amounts of xanthopterin and p-amino-benzoylglutamic acid in the same molecular ratio existing in folic acid, has a complete and specific therapeutic activity almost as rapid as that of folic acid. (5) This indicates that rats can synthesize folic acid from simultaneously administered xanthopterin and p-aminobenzoylglutamic acid.