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Results for “FOLIC ACID DEFICIENCY”

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PubMed1999

The effect of folate deficiency on the hprt mutational spectrum in Chinese hamster ovary cells treated with monofunctional alkylating agents.

Folic acid deficiency acts synergistically with alkylating agents to increase DNA strand breaks and mutant frequency at the hprt locus in Chinese hamster ovary (CHO) cells. To elucidate the mechanism of this synergy, molecular analyses of hprt mutants were performed. Recently, our laboratory showed that folate deficiency increased the percentage of clones with intragenic deletions after exposure to ethyl methanesulfonate (EMS) but not N-nitroso-N-ethylurea (ENU) compared to clones recovered from folate replete medium. This report describes molecular analyses of the 37 hprt mutant clones obtained that did not contain deletions. Folate deficient cells treated with EMS had a high frequency of G>A transitions at non-CpG sites on the non-transcribed strand, particularly when these bases were flanked on both sides by G:C base pairs. Thirty-three percent of these mutations were in the run of six G's in exon 3. EMS-treated folate replete cells had a slightly (but not significantly) lower percentage of G>A transitions, and the same sequence specificity. Treatment of folate deficient CHO cells with ENU resulted in predominantly T>A transversions and C>T transitions relative to the non-transcribed strand. These findings suggest a model to explain the synergy between folate deficiency and alkylating agents: (1) folate deficiency causes extensive uracil incorporation into DNA; (2) greatly increased utilization of base excision repair to remove uracil and to correct alkylator damage leads to error-prone DNA repair. In the case of EMS, this results in more intragenic deletions and G:C to A:T mutations due to impaired ligation of single-strand breaks generated during base excision repair and a decreased capacity to remove O6-ethylguanine. In the case of ENU additional T>A transversions and C>T transitions are seen, perhaps due to mis-pairing of O2-ethylpyrimidines. Correction of folate deficiency may reduce the frequency of these types of genetic damage during alkylator therapy.

Alkylating Agents↗
PubMed1988

Effects of folate deficiency on the metastatic potential of murine melanoma cells.

Experiments were designed to measure the effect of folic acid deficiency on a major determinant of cancer lethality, the propensity to form metastases. Murine B16 melanoma cells (F10 strain) were grown in folate-deficient and -supplemented media. After 3 days, cells in the deficient medium had restricted proliferative capacity, low folate levels by bioassay, increased cell volume, abnormal deoxyuridine suppression tests, accumulation of cells in S phase by flow cytometry, and increased numbers of DNA strand breaks. These folate-deficient cells consistently initiated more pulmonary metastases than control cells when injected into host mice. Cell size did not appear to be a major factor in pulmonary metastasis formation. In vitro growth rates and cloning efficiencies were comparable for cells in both types of medium as was subcutaneous growth of tumors. We conclude that folate deficiency increases the metastatic potential of cultured melanoma cells.

Animals↗
PubMedDate not supplied

Methanol-induced neurotoxicity in pups exposed during lactation through mother: role of folic acid.

Role of folic acid on methanol-induced neurotoxicity was studied in pups at Postnatal Day (PND) 45 exposed to methanol (1%, 2% and 4%, v/v) during lactation through mothers maintained on folic acid-deficient (FD) and folic acid-sufficient (FS) diet. A gradual loss in the body weight gain was observed in the pups exposed to 2% and 4% methanol in the FD group, while FS group exhibited this alteration only at 4% exposure. The assessment of spontaneous locomotor activity (SLA) showing a significant increase in the distance travelled was observed in the 2% and 4% methanol-exposed groups in both the FS and FD animals when compared with their respective controls, but the effect was more marked in the FD group. A significant decrease in the conditioned avoidance response (CAR) was observed in pups exposed to 2% and 4% methanol in the FD group at PND 45. The results also suggest that disturbances in dopaminergic and cholinergic receptors were more pronounced in the FD group as compared to the FS group. A significant decrease in striatal dopamine levels was also observed in the FD group at 2% and 4% methanol exposure, while in the FS group, a significant decrease was exhibited only at 4% methanol exposure. An aberrant increase in the expression of Growth-Associated Protein (GAP-43), a neuron-specific growth-associated protein was observed in pups in the FD group exposed to 2% and 4% methanol, while an increase in the expression of GAP-43 in the FS group was found only at 4% methanol exposure in the hippocampal region as compared to their respective controls. Results suggests that methanol exposure during growth spurt period adversely affects the developing brain, the effect being more pronounced in FD rats as compared to FS rats, suggesting a possible role of folic acid in methanol-induced neurotoxicity.

Animals↗
PubMed1975

[Effects of alcohol on the blood].

Acute alcohol intoxication, particularly in chronic alcohol abusers, leads to qualitative and quantitative changes in all three hemopoietic systems. In addition to a hemolytic effect through various possible mechanisms, functional abnormalities of granulocytes, immunocytes and marcophages and qualitative anomalies of platelets, alcohol exerts a toxic effect on cell production which cannot, or can only partially, be prevented by correction of the frequently demonstrable folic acid deficiency.

Acanthocytes↗
PubMed1986

Anaemia of pregnancy in Mozambique.

To establish the prevalence of anaemia in pregnant women in Mozambique and to determine the locally most important causes of the disease, 881 pregnant women were examined at nine sites in seven of Mozambique's 10 provinces. In Maputo, the capital city, an additional 91 anaemic gravidae were compared to 207 parturients chosen at random. The study comprised interviews, and clinical and laboratory investigations. Between 5 and 15% of the pregnant women at the different sites had haemoglobin (Hb) values below 90 g/l and 58% had levels below 110 g/l. Inspection of mucosal membranes detected almost all the anaemic women with Hb values below 80 g/l. Nulliparous women were more prone to be anaemic. Iron deficiency and malaria were the main causes of anaemia, with malnutrition also contributing. Occasional cases of folic acid deficiency were found among severely anaemic women but no cases of significant deficiency of vitamin B12 were encountered. Sickle cell disease was not found to contribute significantly to anaemia of pregnancy in Mozambique. The mean corpuscular haemoglobin concentration (MCHC) proved more sensitive, under these conditions, than serum ferritin in detecting iron deficiency in anaemic women. Packed cell volume (PCV) analysis may substitute Hb analysis when screening for pregnancy anaemia in Mozambique.

Anemia↗
PubMed1973

Vitamin B12 and the megaloblastic development.

In patients with vitamin B(12) deficiency, phytohemagglutinin-stimulated cultured lymphocytes had little or no thymidylate synthetase activity. Ample activity was found in such lymphocytes from normal individuals and patients with folic acid deficiency or pernicious anemia in remission. It therefore appears that the megaloblastosis that is associated with vitamin B(12) deficiency is related to low thymidylate synthetase activity.

Anemia, Pernicious↗
PubMed2000

Cribra orbitalia in two temporally disjunct population samples from the Dakhleh Oasis, Egypt.

Cribra orbitalia (CO), an osseous sign of anemic stress, occurs in 67% (n = 296) of the pre-Roman (n = 153) and Roman (n = 143) period crania from the Dakhleh Oasis, Egypt. CO is primarily a childhood condition in these samples, and its prevalence is significantly higher in virtually all cohorts in the pre-Roman group, including among females, who display higher rates of active lesions. This temporal trend suggests that the underlying causative factors (i.e., synergism between disease and nutrition) were less pervasive in the Roman period. In both population samples, anemic stress develops in some perinates prior to the expected minimum age for the development of iron deficiency anemia. This suggests additional causes of anemic stress in the Dakhleh population. A strong candidate is folic acid deficiency and its concomitant, megaloblastic anemia, which results from weaning of infants on goat's milk, a known practice in ancient Egypt. The putative incorporation of other food items in the weanling diet, particularly honey, a confirmed source of C. botulinum, represents yet another retrospective data source to help understand the epidemiological profile of cribra orbitalia in this population. Comparative data from other Egyptian populations, though limited, show similar patterns, however, they display a lower prevalence than the data from Dakhleh.

Adolescent↗
PubMed1962

Excretion of formimino-glutamic acid in steatorrhoea.

Minor degrees of folic acid deficiency are very common in idiopathic steatorrhoea. The urinary excretion of formimino-glutamic acid (Figlu) after a histadine load is a satisfactory means of detecting this deficiency and may be used as a screening test for idiopathic steatorrhoea.

Celiac Disease↗
PubMed2000

[The importance of folic acid in current medicine].

Lately, folic acid deficiency is gaining a predominant role in the pathogenesis of congenital malformations and cardiovascular diseases in adults. The planning of individual and population preventive strategies for these diseases must consider this deficiency. This paper reviews the anatomical, biochemical and molecular bases of neural tube defects and cardiovascular diseases in adults. In these two frequent diseases, folic acid supplementation has shown a clear cut protective effect.

Adult↗
PubMed2001

Micronutrients in pregnancy.

Vitamins and minerals, referred to collectively as micronutrients, have important influences on the health of pregnant women and the growing fetus. Iron deficiency results in anemia which may increase the risk of death from hemorrhage during delivery, but its effects on fetal development and birth outcomes is still unclear. Folic acid deficiency can lead to hematological consequences, pregnancy complications and congenital malformations, but again the association with other birth outcomes is equivocal. Zinc deficiency has been associated in some, but not all studies with complications of pregnancy and delivery, as well as with growth retardation, congenital abnormalities and retarded neurobehavioral and immunological development in the fetus. Iodine deficiency during pregnancy results in cretinism and possible fetal wastage and preterm delivery. Deficiency of other minerals such as magnesium, selenium, copper, and calcium have also been associated with complications of pregnancy, childbirth or fetal development. Deficiencies of vitamins other than folate may likewise be related to such complications; and vitamin A or beta-carotene supplements in pregnancy reduced maternal mortality by 50 % in a controlled trial in Nepal. Additional research is need on the prevalence of such deficiencies and their consequences and on cost-effective public health interventions for their control.

Anemia, Iron-Deficiency↗
PubMed1993

[Erythrocyte mean corpuscular volume of psychiatric patients].

It has been observed clinically that the mean corpuscular volume (MCV) of erythrocytes is increased in psychiatric patients, but this phenomenon has not been investigated. We therefore compared the MCV of 177 patients in our psychiatric day care ward and in our psychiatric outpatient clinic. The MCV of these psychiatric patients, and especially that of the outpatients, were significantly greater than that of normal controls. No association was found between MCV and sociodemographic or clinical variables. The sensitivity of a high MCV level as a diagnostic for folic acid deficiency was 42.9%, with a specificity of 80.6%. The sensitivity of a high MCV level as a diagnostic for vitamin B12 deficiency was 23.1%, with a specificity of 79.4%.

Erythrocyte Indices↗
PubMed2007

Glomerular filtration rate as measured by serum cystatin C is an important determinant of plasma homocysteine and serum methylmalonic acid in the elderly.

OBJECTIVES: To explore the dependence of glomerular filtration rate (GFR) on plasma total homocysteine (tHcy) and serum methylmalonic acid (MMA), as well as the consequences for the diagnosis of cobalamin and/or folic acid deficiency in an elderly community-dwelling population. DESIGN AND SETTING: Population-based study of 209 community-dwelling subjects, mean age 76 years. INTERVENTIONS: Four months' treatment study with oral vitamin B(12), folic acid and B(6) or placebo. MAIN OUTCOME MEASURES: Determinants of tHcy and MMA: cystatin C as a marker of GFR and serum/plasma concentrations of vitamin B(12) and folate, age and sex. RESULTS: Elevated cystatin C (>1.55 mg L(-1)) was found in 31.3% (men) and 13.0% (women). Elevated tHcy (> or = 16 micromol L(-1)) occurred in 53% and elevated MMA (> or = 0.34 micromol L(-1)) in 11% of all subjects. When GFR was taken into consideration, the proportion of elevated tHcy was reduced to 10% (20/209), whilst the proportion of elevated MMA was unchanged. Cystatin C was correlated with tHcy (r = 0.45, P < 0.001) and with MMA (r =0.28, P < 0.001), independently of vitamin B(12)- and folate status. According to multiple regression, independent predictors for tHcy were plasma folate (15%), cystatin C (11%) and vitamin B(12) (4%), and for MMA, cystatin C (8%) and vitamin B(12) (2%). CONCLUSIONS: The prevalence of elevated tHcy may be overestimated in elderly populations unless GFR is taken into account. Nomograms for evaluation of tHcy and MMA in relation to both cystatin C and serum creatinine are presented.

Aged↗
PubMed1983

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.

Amino Acids↗
PubMed1977

Hematologic and oncologic implications of alcoholism.

Hematologic complications of alcoholism are common. Folic acid deficiency can lead to pancytopenia. Iron-deficiency anemia, various hemolytic states, and abnormalities in both function and number of platelets can occur. There is a great deal of interest in the adverse effects of alcohol on pyridoxine (vitamin B6) and folic acid metabolism. Malignant disease often complicates alcoholism and should always be suspected.

Alcoholism↗
PubMed1979

Diagnosis and management of folate deficiency in low birthweight infants.

Significant folate deficiency in 14 out of 37 preterm infants of birthweights 2.0 kg or less was found to be reliably and most conveniently diagnosed by abnormal morphological changes in peripheral blood and confirmed by the response to folic acid. Deficiency appeared to be more common in light-for-dates infants including the smaller of twins. Neither the clinical status nor the levels of haemoglobin or erythrocyte folate was a reliable guide to the presence of megaloblastic erythropoiesis in the very young preterm infant. 100-200 microgram folic acid a day, orally or IM, may be required to ensure an optimal haematological response, and this would be appropriate for therapeutic trial if the diagnosis is in doubt. This amount would also replenish tissue folate stores; larger doses are likely to exceed the requirements of small infants.

Female↗
PubMed2003

RAEB-t in young adults--a rare entity.

Refractory anemia with excess blasts in transformation (RAEB-t) in young adults is a rare entity. RAEB-t presenting with megaloblastic erythropoiesis should be differentiated from nutritional B12 and folic acid deficiency and from acute erythroleukemia. We report two cases in the present article.

Adult↗