To evaluate the implication of methymalonic acid (MMA) in the early diagnosis of neural tube defects (NTD), a quantitative assay for MMA was established by using gas chromatography-mass spectrometry with stable isotope of MMA as an internal standard. Amniotic fluid and maternal urine MMA concentration, maternal serum folate, red blood cell folate and vitamin B12 levels were measured in the middle term of NTD-affected and normal pregnancies. Amniotic fluid and maternal urine MMA concentrations in the middle term of NTD affected pregnancies (1.4 +/- 0.9 micromol/L, and 22.1 +/- 12.6 nmol/micromol creatinine) were significantly higher than that of normal pregnancies (1.0 +/- 0. 4 micromol/L, and 2.5 +/- 1.1 nmol/micromol creatinine). There was no significant difference between normal and NTD pregnancies for serum folate, red blood cell folate and vitamin B12 levels. The results suggested that MMAs in amniotic fluid and maternal urine are sensitive markers for early diagnosis of NTD. Vitamin B12 is an active cofactor involved in the remethylation of homocycteine and its deficiency is an independent risk factor for NTD. MMA is a specific and sensitive marker for intracellular vitamin B12 deficiency. This study suggests that it is necessary to monitor the vitamin B12 deficiency and advocates vitamin B12 supplementation with folate prevention program.
Amniotic Fluid/*chemistry ; Biological Markers/analysis ; Biological Markers/urine ; Folic Acid/blood ; Methylmalonic Acid/analysis ; Methylmalonic Acid/*urine ; Neural Tube Defects/*diagnosis ; Neural Tube Defects/metabolism ; Pregnancy Trimester, Second ; *Prenatal Diagnosis ; Vitamin B 12/blood

To explore immune intervention effects of the combined use of cycloporin A (CsA) and 1, 25-dihydroxyvitamin D3[1,25(OH)2D3] at low doses on experimental autoimmune thyroiditis (EAT), porcine thyroglobulin (pTG) was injected into a CBA mouse at the dose of 100 micrograms on day 0 and day 14 to establish the model of EAT. The immune prevention group from day 0 to day 28, and treatment group from day 10 to day 38 were daily administered CsA (10 mg/kg) intragastrically and/or 1,25(OH)2D3 (0.2 microgram/kg) i.p. After immunized by pTG, the mice were sacrificed on day 28 and day 38 to examine their thyroid gland pathologically, and to check the levels of serum porcine thyroglobulin antibodies (pTGAb), porcine thyromicrosomal antibodies (pTMAb). The incidences of EAT in the immune prevention group and treatment group, with administration of low dose of CsA and 1,25(OH)2D3, were decreased respectively by 44.44% and 37.50%. Those of severe disease in the two groups were decreased respectively by 71.43% and 60.32%. The levels of serum pTGAb and pTMAb in the immune prevention group were lower than those of the positive control group. It was concluded that combined use of CsA and 1,25(OH)2D3 at low doses could effectively prevent EAT with a synergic effect.
Animals ; Antibodies ; blood ; Calcitriol ; therapeutic use ; Cyclosporine ; therapeutic use ; Drug Synergism ; Female ; Mice ; Mice, Inbred CBA ; Thyroglobulin ; immunology ; Thyroiditis, Autoimmune ; drug therapy ; immunology ; prevention & control

To evaluate the implication of methymalonic acid (MMA) in the early diagnosis of neural tube defects (NTD), a quantitative assay for MMA was established by using gas chromatography-mass spectrometry with stable isotope of MMA as an internal standard. Amniotic fluid and maternal urine MMA concentration, maternal serum folate, red blood cell folate and vitamin B12 levels were measured in the middle term of NTD-affected and normal pregnancies. Amniotic fluid and maternal urine MMA concentrations in the middle term of NTD affected pregnancies (1.4 +/- 0.9 micromol/L, and 22.1 +/- 12.6 nmol/micromol creatinine) were significantly higher than that of normal pregnancies (1.0 +/- 0. 4 micromol/L, and 2.5 +/- 1.1 nmol/micromol creatinine). There was no significant difference between normal and NTD pregnancies for serum folate, red blood cell folate and vitamin B12 levels. The results suggested that MMAs in amniotic fluid and maternal urine are sensitive markers for early diagnosis of NTD. Vitamin B12 is an active cofactor involved in the remethylation of homocycteine and its deficiency is an independent risk factor for NTD. MMA is a specific and sensitive marker for intracellular vitamin B12 deficiency. This study suggests that it is necessary to monitor the vitamin B12 deficiency and advocates vitamin B12 supplementation with folate prevention program.
Adult ; Amniotic Fluid ; chemistry ; Biomarkers ; analysis ; urine ; Female ; Folic Acid ; blood ; Humans ; Methylmalonic Acid ; analysis ; urine ; Neural Tube Defects ; diagnosis ; metabolism ; Pregnancy ; Pregnancy Trimester, Second ; Prenatal Diagnosis ; Vitamin B 12 ; blood