Maternal folate intake and levels of folate in milk, serum and red cells were assessed in 57 healthy, lactating women, ages 22-38 years, throughout early (0-6 months) and later (7-23 months) lactation. Average maternal folate intake from diet alone was 212 µg/day or 78.5% RDA (1989) and mean total folate intake from diet and supplements was 314% RDA (878 µg/day) at 0-6 months and 238% RDA (620 µg/day) at >6 months. Human milk folate was sufficient to meet the RDA (1989) for infants. Milk folate was not related to maternal folate intake, maternal serum or red cell folate and was unaffected by extended lactation (7-23 months), perhaps at the expense of maternal folate stores. Compared with early lactation, serum folate decreased (p=0.0004) and red cell folate tended to decrease (p=0.08) in later lactation and were both increased by folate supplementation (p < 0.001).Level of folic acid supplementation appeared to predict red cell folate concentration. An average of 884 µg supplemental folate/day was associated with red cell folate levels >400 ng/mL, which have previously been reported as optimal for prevention of folateresponsive neural tube defects. The addition of an 880 µg/day folic acid supplement to the diet of lactating women may raise red cell folate concentrations of lactating women to protective levels. / Department of Family and Consumer Sciences

Various hormones have been studied as regards prediction of pregnancy outcome after infertility treatment, but no ideal candidate has been found. Folate and genetic variations in folate metabolism have also been associated with infertility, but it remains unclear how these factors affect IVF pregnancy outcome. It is known that infertility is associated with active folic acid supplement use, but the effect of socioeconomic and lifestyle factors on folic acid supplement use in infertile women has not been well investigated. The overall aim of this work was to obtain information on the prediction of live birth, and to study factors affecting the role of folate and folic acid intake in relation to IVF pregnancy outcome. Infertile women with various infertility diagnoses were studied. Healthy, fertile non-pregnant women were used as controls in three of the studies. Blood samples were taken for assay of eight different hormones, folate and homocysteine, and for genomic DNA extraction. A questionnaire was used to assess background data and use of folic acid supplements. Twenty-four-hour recall interviews were performed for validation of the questionnaire. The studied hormones were not good predictors of live birth. The best predictor was age of the women, together with ovulatory menstrual cycles, and thyroid-stimulating hormone and anti-Müllerian hormone (AMH) status. Well-educated women, high-status employed women, and married and infertile women used the most folic acid supplements. Infertile women had better folate status than fertile women. However, pregnancy outcome after infertility treatment was not dependent on folic acid intake, folate status, genetic variation of 5,10-methylenetetrahydrofolate reductase or socioeconomic status. In conclusion, AMH levels vary less than those of other hormones during the menstrual cycle, and AMH could be used as a predictive marker of live birth together with age and ovulation. Folate might play a minor role in IVF pregnancy outcome, but the importance of folate as regards other health perspectives should not be forgotten.

Statement of problem: We have shown that the C677T 5,10 methylenetetrahydrofolate reductase (MTHFR) variant is associated with elevated maternal serum α-fetoprotein (MSAFP), the most common screening test for neural tube defects (NTD). Therefore, past contradictory studies of NTDs and C677T MTHFR may have been biased because of changes in case populations after prenatal diagnosis and termination of pregnancy. Further, an unexplained elevation of MSAFP is known to increase the risk for later pregnancy complications. Is the C677T MTHFR variant a predisposing genetic variant for both NTDs and later complications of pregnancy? Methods: A retrospective study of women with pregnancies resulting in NTD outcome and women with unexplained elevations of MSAFP was undertaken. Women and their partners were genotyped for the C677T MTHFR allele. Couples with a pregnancy resulting in a NTD outcome were compared to couples whose pregnancy outcome did not involve. Couples with unexplained elevations of MSAFP who did and did not have later complications of pregnancy were also compared. Allele frequencies for all groups were then compared against the previously established Manitoba population allele frequency (based on 977 consecutive newborn metabolic screening bloodspots). A review of all studies of NTDs and association with the C677T MTHFR variant was undertaken to determine if the association between the variant and MSAFP is a source of bias. NTD incidence was examined before and after folic acid food fortification introduced in Canada in 1999. Results: There is an increase in the allele frequency of the C677T MTHFR variant in parents with an unexplained elevated MSAFP followed by later complications of pregnancy. The C677T MTHFR variant is also a contributing genetic factor to NTDs worldwide. The incidence of NTDs in Manitoba has decreased by 37% since food fortification with folic acid was introduced. Conclusions: The C677T MTHFR variant is a contributing genetic factor to both later complications of pregnancy after an unexplained elevation of MSAFP and to NTDs. This variant is folate sensitive and folic acid fortification has reduced the incidence of NTDs.

Tyrimo tikslas – išvystyti analitinę metodiką tinkamą geležies sulfato, folio rūgšties ir cianokobalamino įvertinimui jiems esant daugiakomponenčio vaistinio preparato sudėtyje. Uždaviniai: surinkti informaciją apie anemiją ir medicinoje vartojamus antianeminius preparatus; apžvelgti plačiausiai naudojamus folio rūgšties, cianokobalamino ir geležies tyrimo metodus; pasirinkta metodika atlikti daugiakomponenčio preparato Ferro-folgamma komponentų atskyrimą; pasirinktais metodais identifikuoti cianokobalaminą, folio rūgštį, geležies sulfate; atlikti folio rūgšties ir geležies kiekybinę analizę. Metodai: efektyvioji skysčių chromatografija, spektrofotometrija. Tyrimo objektas – vaistinis preparatas “Ferro-folgamma”, kurio vienoje kapsulėje yra 100 mg bevandenio dvivalentės geležies sulfato (atitinka 37 mg geležies), 5 mg folio rūgšties, 10 μg cianokobolamino. Tyrimo rezultatai. ESC su diodų matricos detektoriumi metodika atliktas folio rūgšties ir cianokobalaminio atskyrimas ir nustatymas. Vitaminų atskyrimas pasiektas naudojant 150×4.6 mm 3 µm ACE18 kolonėlę, judriąją fazę fluoracto rūgštį (0.1 proc.) ir acetonitrile, judrios fazės tekmės greičiui esant 1.0 ml/min. Folio rūgšties detekcija atlikta prie 287 nm ilgio bangos, nustatyta aptikimo riba – 0.04 µg/ml, kiekybinio nustatymo riba – 0.13 µg/ml. Cianokobalamino detekcija atlikta prie 360 nm bangos ilgio, nustatyta aptikimo riba – 0.474 µg/ml, kiekybinio nustatymo riba – 1.57 µg/ml. Spektrofotometriškai kiekybiškai nustatyta... [toliau žr. visą tekstą] / Aim – to develop an analytical method that would be suitable for evaluating iron sulphate, folic acid and cyanocobalamin in the multicomponental drug. Objectives: gather information about anemia and antianemic drugs used in medicine; review the most often used methods of folic acid, cyanocobalamin and iron; carry out the separation of “Ferro-folgamma” components; identify cyanocobalamin, folic acid and iron sulphate; carry out a quantitive determination of folic acid and iron. Methods: high-performance liquid chromatography, spectrophotometry. Object: preparation “Ferro-folgamma” containing 100 mg anhydrous iron sulphate (37 mg of iron), 5 mg folic acid and 10 μg cyanocobalamin. Results: Identification and determination of folic acid and cyanocobalamin in pharmaceutical preparation was developed using HPLC with photodiode array detector (PDA). Folic acid and cyanocobalamin were separated on a ACE18 column (150×4.6 mm, 3 µm particle size) with a gradient elution of mobile phase consisting of 0.1% trifluoroacetic acid and acetonitrile. The separation was achieved with a flow rate of 1.0 ml/min. Detection of folic acid was performed at 287 nm wavelength, limit of detection – 0.04 µg/ml, limit of quantification – 0.13 µg/ml. Detection of cyanocobalamin was performed at 360 nm wavelength, limit of detection – 0.474 µg/ml, limit of quantification – 1.57 µg/ml. The absorbance of the iron complex was measured spectrophotometrically at 423 nm. Conclusions: HPLC/PDA method for... [to full text]

A new class of polymer coated lanthanide fluoride nanoparticle aggregates (NPAs) was developed as potential MRI contrast agents. The NPA synthesis has been perfected to control the size distribution and optimize relaxivities. Polyacrylic acid was used as a stabilizing polymer, and was conjugated to folic acid to improve targeting to SK-BR-3 breast cancer cells. Terbium was incorporated in the synthesis to study the passive and active targeting properties of NPAs. Through a series of microscopy experiments, a significant difference in uptake between NPAs with and without targeting moieties occurs after 48 hours of incubation. The relaxivity of the optimized nanoparticles was measured to be 56 s-1(mg/ml)-1 using a 1.5 T scanner, which may be compared to that of the commercially available Gd3+-DTPA [R1 = 7 s-1(mg/ml)-1]. Abdominal perfusion studies in rats also demonstrated that the NPAs provide better contrast of the vasculature than Gd3+-DTPA does at the same mass concentration.

The relationship between colorectal cancer (CRC) and folate metabolism is complex. Dietary folate, depending on the timing and dose, may either prevent or enhance tumour initiation and/or growth, and polymorphisms in the genes encoding folate-metabolising enzymes may also modulate risk. In this thesis, the Apcmin/+ mouse model of CRC was used to investigate the effect of nutritional and genetic disturbances in folate metabolism on tumourigenesis and to examine various mechanisms. / The reduced folate carrier I (RFC1) is responsible for the cellular uptake and intestinal absorption of folate, primarily the 5-methyltetrahydrofolate (5-methylTHF) derivative. Methionine synthase (MTR) uses 5-methylTHF to remethylate homocysteine to methionine, which may be activated and used to methylate substrates such as DNA. 5-MethylTHF is also the product of the methylenetetrahydrofolate reductase (MTHFR)-catalysed reduction of 5,10-methyleneTHF, which is also used to convert dUMP to dTMP. / Adenoma number and load were reduced in Rfc1+/-Apc min/+ mice, compared with Rfc1+/+Apc min/+ mice, but were similar in Mtr+/-Apc min/+ and Mtr+/+ Apcmin/+ mice. Neither Rfc1 nor Mtr genotype affected global DNA methylation, apoptosis or plasma homocysteine (tHcy) levels. In the experiments involving Mtr mice, dietary folate deficiency increased adenoma number, plasma tHcy, and apoptosis, and decreased global DNA methylation. Neither Mtr nor Rfc1 genotype affected the dUTP/dTTP ratio in the intestine of mice not predisposed to adenoma formation. / Adenoma number was decreased in Mthfr+/-Apc min/+ mice (compared with Mthfr+/+Apc min/+ mice) and in Mthfr+/+Apc min/+ offspring of Mthfr+/- mothers (compared with Mthfr+/+Apcmin/+ offspring of Mthfr+/+ mothers). A folate-deficient diet, when initiated prior to conception, significantly decreased adenoma number and decreased global DNA methylation. Overall, adenoma number was inversely correlated with plasma tHcy, dUTP/dTTP ratio and apoptosis. When initiated at three weeks of age, a folate-enriched diet significantly increased adenoma number in Apcmin/+ mice. In the intestines of mice not predisposed to adenoma formation, Mthfr deficiency decreased, and folic acid deficiency increased, the dUTP/dTTP ratio. / These results support the evidence that MTHFR polymorphisms are protective in CRC tumourigenesis and that depending on stage or predisposition, folate may inhibit or enhance tumour growth.

Glutamate formiminotransferase deficiency (OMIM 229100) is an autosomal recessive disorder marked by clinical heterogeneity. The severe phenotype, first identified in patients of Japanese descent, includes high levels of formiminoglutamate (FIGLU) in the urine in response to histidine loading, megaloblastic anemia, and mental retardation. The mild phenotype is marked by high levels of FIGLU in the urine in the absence of histidine loading, mild developmental delay and no hematological abnormalities. The gene for human glutamate formiminotransferase-cyclodeaminase consists of 15 exons and is located at 21q22.3. The protein consists of a tetramer of dimers, with dimerization essential for both formiminotransferase and cyclodeaminase activity. / Genomic DNA extracted from cell lines from three patients with suspected glutamate formiminotransferase deficiency was analyzed by PCR and sequencing of individual exons. Cell lines WG 1758 and WG 1759 are from two siblings of Germanic descent. Both siblings are heterozygous for the mutations c457 C &rarr; T and c940 G &rarr; C. The c457 C &rarr; T changes a conserved arginine to a cysteine in a loop involved in the binding of formiminotetrahydrofolate to the enzyme. The c940 G &rarr; C mutation converts an arginine to a proline in an alpha-helix essential for the dimerization of the formiminotransferase domain. Cell line WG 1795 is from a patient of Danish descent. The patient appears to be hemizygous for a c1033 insG mutation. Quantitative PCR suggests the presence of a deletion on the other chromosome, which minimally encompasses exon 9. All of the FTCD gene changes were absent in 100 control individuals (200 alleles).

Thesis (Ph. D.)--Oregon State University, 2008. / Includes bibliographical references. Also available online (PDF file) by a subscription to the set or by purchasing the individual file.

Thesis (Ph. D.)--Oregon State University, 2008. / Includes bibliographical references.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2003. / Härtill 5 uppsatser.