[Does folic acid encourage tumor growth?].
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Twenty-two patients with metastatic colorectal cancer were treated with a regimen of 5-fluorouracil 600 mg/m2 (maximum, 1.0 g) i.v./week and folic acid 140 mg/m2 i.v. given 1 h prior to the 5-FU. This study was undertaken in an attempt to confirm the in vitro finding that inhibition of thymidylate synthetase by 5-fluorouracil is prolonged by the presence of folates. There were four partial responses (18%) with mean duration 4 months. Dose-limiting toxicity was enteritis, seen in 12 patients (58%), and causing hospitalization in seven patients. Enteritis was shown to be due to the folic acid in most patients. Two patients died from leukopenia, enteritis, and sepsis. Mean serum folate levels at the time of 5-FU injection were 36 microM. This regimen is no more effective than 5-FU alone and has significantly more serious toxicity. Further investigation of this regimen is not recommended.
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Oxidative stress seems to play an important role in the pathophysiology of essential hypertension. Due to its antioxidant features, we studied the protective action of folic acid in hypertensive patients, their food supplemented for 2 weeks with this vitamin. Several oxidative stress parameters were measured in the serum of these patients. The results show that folic acid supplementation improves levels of oxidative stress markers in individuals with hypertension, overall in those patients whose initial parameter values were highest.
Most international trials support the recommendation that all women planning or at risk of pregnancy take a daily multivitamin supplement containing folic acid, beginning one month before conception and continuing through the first trimester for primary prevention of neural tube defects and other congenital malformations. Recently an intervention project started also in Italy, in order to support and maintain the periconceptional supplementation and to evaluate the efficacy of a national preventive campaign on parents' behaviour.
BACKGROUND: Upon discovering an NTD incidence rate of 27/10,000 in a Texas border county, the Texas Department of Health initiated folic acid intervention for prevention of recurrent NTDs in this predominantly Mexican-American population. This paper describes compliance of this population with USPHS folic acid recommendations and the impact of supplementation on pregnancy outcomes. METHODS: Based upon information from active surveillance, field teams personally contacted women having NTD-affected pregnancies to enroll them in FA intervention. Enrollees were provided FA at home visits at 3-month intervals throughout the project. RESULTS: Of 405 women identified with NTD-affected pregnancies, 299 (73.8%) enrolled in the intervention. One hundred ninety-three pregnancies occurred among 138 women. FA supplementation of 0.4 mg/day or more occurred during the last month preconception in 161 (83.4%) of the 193 pregnancies. No NTDs were detected in the 130 livebirths to women who received supplementation nor were NTDs detected in the 23 supplemented women who experienced pregnancy loss. CONCLUSIONS: Supplementation was successful in preventing recurrent NTDs in Mexican-American women.
A membrane preparation from Enterococcus hirae contained UDP and methyl-UDP (mUDP) monosaccharides. This preparation, when incubated with combinations of folic acid, L-serine, and S-adenosyl-L-methionine in a reaction system containing UDP-glucose, promoted synthesis of certain mUDP sugars. Folic acid and serine produced mUDP-glucose and mUDP-rhamnose; S-adenosylmethionine produced mUDP-glucose, mUDP-mannose, and mUDP-fucose.
Facioscapulohumeral muscular dystrophy (FSHD) is associated with a contraction of the D4Z4 allele on chromosome 4qter. There is also marked DNA hypomethylation of the D4Z4 allele. The DNA hypomethylation may have a central role in the pathogenesis of FSHD. Supplemental folic acid can boost DNA methylation. We evaluated the effect of oral folic acid and methionine supplementation on the methylation level of 4qter D4Z4 alleles in peripheral-blood lymphocytes of nine patients affected with FSHD and six healthy controls. Methylation levels did not change, while recommended serum-folate concentrations were reached.
The experiment was undertaken to determine the effects of i.m. injections of vitamin B(12) on lactational performance of primiparous dairy cows fed dietary supplements of folic acid and rumen-protected methionine from 4 to 18 wk of lactation. Fourteen primiparous Holstein cows were assigned to 7 blocks of 2 cows each, according to milk production during the third week of lactation. All cows were fed a basal diet supplemented daily with rumen-protected methionine (18 g of supplement, to bring the estimated supply of methionine to 2.2% of metabolizable protein) plus folic acid (4 mg per kg of BW). Within each block, the cows received a weekly i.m. injection (2 mL) of saline or 10 mg of vitamin B(12). Milk production was recorded daily. Milk and blood were sampled every 2 wk. Supplementary vitamin B(12) increased energy-corrected milk from 25.8 to 29.0 (SE 1.6) kg/d, as well as milk yields of solids [3.52 to 3.90 (SE 0.22) kg/d], fat [0.87 to 1.01 (SE 0.06) kg/d], and lactose [1.48 to 1.64 (SE 0.11) kg/d]. Supplementation also increased concentrations and amounts of vitamin B(12) secreted in milk but had no significant effect on dry matter intake and concentrations and amounts of folates in milk. Packed cell volume, blood hemoglobin, and serum vitamin B(12) were increased by supplementary vitamin B(12), whereas serum methylmalonic acid was decreased. Serum concentrations of sulfur amino acids were unchanged by treatment. These findings support the hypothesis that, in early lactation, supply of vitamin B(12) was not optimal and limited the lactation performance of the cows.
The plasma clearance of intravenously administered folic acid was abnormally rapid in all of five patients studied with untreated hyperthyroidism; in three, the basal serum L. casei folate level was subnormal. Four of these patients and another patient were studied at various intervals after partial or complete correction of the hyperthyroid state. Partial correction resulted in a continued fast clearance in one patient, a return to borderline-normal values in the second, and a normal clearance in the third. Complete euthyroidism was achieved in two patients; their clearance values had returned to borderline-normal at this time. In two patients studied after partial correction, the serum L. casei folate levels had become normal whereas the clearance values remained abnormally rapid. These findings suggest that hyperthyroidism in man is associated with depletion of folate stores and subclinical deficiency of this vitamin. This is attributed to an increased demand for folic acid in the hypermetabolic state.
Forty-one pregnant patients with severe iron deficiency anaemia were treated with either intravenous iron-dextran (Imferon; Fisons) or intravenous iron plus folic acid. There was no difference in the rate of response or the eventual total response in the two groups, suggesting that iron therapy does not unmask or produce a relative folic acid deficiency.
A range of 2-acrylamidopyridines, showing subtle differences in solution binding toward carboxylic acids, has been investigated as functional monomers in molecular imprinting. Imprinting of N-Z-L-glutamic acid with one such monomer is shown to be effective in the creation of a molecularly imprinted polymer (MIP) with recognition properties for its template and also for larger molecules containing glutamic acid residues. In comparison to a MIP prepared via a more "traditional" approach, the new polymeric receptors exhibit reduced nonspecific binding. The new receptors are compared with previously reported urea-based receptors targeting the glutamic acid residue and receptors targeting the pteridine substructure of folic acid.
OBJECTIVE: The aim of the study was to analyze the incidence of neural tube defects in Lublin Province between 1990 and 2000 after application of primary prevention with folic acid. MATERIAL AND METHODS: A total of 293,039 newborns were analyzed. RESULTS: Neural tube defects were diagnosed in 53 newborns. CONCLUSION: Reduction of frequency of meningocele was shown after application of primary prevention with folic acid in 1998. Meningoceles were most frequent in 1992 (1.32/1000) and in 1998 frequency of these defects was reduced and in 2000 was down to 0.62/1000 births.
To investigate a newly described model for differentiated small intestinal function, folic acid uptake characteristics were examined in the human colon carcinoma cell line, Caco-2. Monolayers of this cell line spontaneously exhibit structural and functional differentiation patterns characteristic of mature enterocytes, with the appearance of brush border microvilli and high activity levels of the enzymes associated with the brush border. Our results concur with other models of folic acid uptake that emphasize the importance of intraluminal factors on micronutrient absorption. Folate uptake declined rapidly between pH 5.8 and 7.5, and was dependent on the initial folate concentration in the media. A dual uptake process is suggested, with a high rate of uptake at folate concentrations below 20 nmol/ml and linear uptake characteristics at higher concentrations.
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