Barbara DeAngelis

Role of placenta in maternal-fetal vitamin transfer in humans

Vitamins B12, B6, biotin, folate, thiamine, riboflavin, pantothenate, and nicotinate were determined in maternal and fetal blood and placental tissue of normovitaminemic and hypovitaminemic mothers who disclaimed supplemental vitamin intake during pregnancy. No biotin or pantothenate deficits were observed in the gravidas. Hypovitaminemic mothers transferred less B12, folate, and B6 to the fetus and placenta than normovitaminemic mothers. Vitamins given by mouth increased maternal fetal, and placental levels of folate, but B6 increased only in maternal blood and the placenta; biotin and pantothenate increased only in fetal blood. Except for riboflavin, nicotinate, and pantothenate, the intramuscular administration of vitamins increased the levels of other vitamins in maternal and fetal blood and placental tissue. Results suggest that the placenta stores vitamins and the tissue vitamin receptors must be saturated before adequate transfer of vitamins to the fetus occurs.

Cobalamin (Vitamin B12) and Holotranscobalamin Changes in Plasma and Liver Tissue in Alcoholics with Liver Disease

OBJECTIVE We wanted to know if alterations in plasma cobalamin (B12) concentration and B12 carriers, e.g., holotranscobalamins (holo TC), occur in blood and liver tissue from patients with severe alcoholic liver disease. Our purpose was to test the hypothesis that liver disease may disrupt B12 distribution. METHOD Total B12, as well as B12 bound to transcobalamin I, II, III (holo TC), were measured to determine their concentration in plasma and in liver tissue; Poteriochromonas malhamensis--a protozoan reagent served to measure only metabolically active (true) B12. Total B12 as distributed in holo TC in plasma and liver tissue of healthy subjects (controls) were compared to patients with severe alcoholic liver disease. RESULTS Severe liver disease initiates highly elevated B12 levels in plasma and a lowered liver tissue total B12 concentration. The percent of B12 distributed to holo TC II is significantly depleted during liver disease. In contrast, holo TC I and III are elevated in plasma during liver disease and contain more B12 than controls. Total B12 and B12 distributed to TC are lower in diseased liver tissue. CONCLUSION Severe alcoholic liver disease involves leakage of total B12 from liver tissue into the plasma. Holo TC I and III concentration increases in plasma; this preserves the high plasma B12 from being excreted. However, plasma holo TC II B12 distribution is decreased, indicating that there is a depression of exogenous B12 entering the plasma and tissues. In severe liver disease, liver tissue B12 binding and storage by TC is disrupted and causes B12 to leak out of the liver into the circulation. Eventually liver disease could produce enough severe tissue B12 deficits to cause metabolic dysfunction despite elevated plasma total B12. Elevation of plasma B12, accompanied by a lowering of holo TC II distribution, seemed to be a useful index of liver disease severity suggesting preventive treatment.

Vitamin levels in low-birth-weight newborn infants and their mothers

The cord blood of 50 normal-birth-weight neonates (more than 2,500 grams) and 50 low-birth-weight neonates (less than 2,500 grams) and the respective mothers blood were analyzed for folate, vitamin B6, riboflavin, nicotinate, pantothenate, thiamin, biotin, vitamin B12, vitamin A, and beta-carotene concentrations at parturition. No mothers had received supplemental vitamin intake. Except for vitamin A and beta-carotene, maternal vitamin levels were lower than those of neonates in all instances. Vitamin levels in the blood of low-birth-weight neonates were the same of those of normal-birth-weight infants except for significantly lower folate, vitamin B12, and pantothenate levels.

The cell content and secretion of water-soluble vitamins by several freshwater algae.

Three green algae, Chlamydomonas reinhardii, Chlorella vulgaris and Scenedesmus obliquus, and one blue-green alga, Anabaena cyclindrica, were grown in chemically defined media. All the algac examined contained folates, β-carotene and vitamins C and E; several of the B-vitamins and vitamin A were found in varying amounts in some but not in all the algae examined. All the green algae secreted significant amounts of folate and biotin and all but Scenedesmus secreted pantothenate into their growth medium; Anabaena secreted folate and pantothenate.

Vitamins and other metabolites in various sera commonly used for cell culturing

Many cell culture media use different sera to enhance growth. We assayed vitamins and some related metabolites in different sera and identified the concentration of: thiamin, biotin, folates, riboflavin, pantothenates, nicotinates, vitamins B6, B12, A, E. C, and carotenes and some related metabolites: biopterins, free inositol, free and total choline, total carnitines in chicken, horse, rabbit, goat, pig, calf, newborn calf, fetal calf and human sera. Results indicate that vitamin and metabolite concent of different sera vary. Such variations could produce fluctuant effects on cell culturings if the metabolite content of the serum is not documented.

Vitamin Profile of 563 Gravidas during Trimesters of Pregnancy

Objective: Gestation imposes metabolic stress on the mother which heightens as pregnancy progresses. The need for quantifying circulating vitamins is important for identifying pitfalls in metabolic imbalance and nutritional status. For this reason we wanted to analyze blood vitamin concentrations of B12, thiamin, biotin, pantothenate, B6, niacin, riboflavin, folate, vitamins A, C, E and total carotenes to determine if imbalances occur during the trimesters of pregnancy. Methods: We randomly selected 563 gravidas who volunteered for this study from the obstetrical clinic of New Jersey Medical School; 132 were in 1st trimester, 198 were in 2nd trimester, and 233 were in 3rd trimester. All were healthy, taking a good diet and supplemented with vitamins. Blood, from an antecubital vein, was analyzed for thiamin, biotin, B12, B6, pantothenate, riboflavin, nicotinate, folates, vitamins A, E, C and total carotenes. Gravidas were classified as being normovitaminemic, hypervitaminemic or hypovitaminemic compared with blood vitamins seen in healthy non-pregnant, non-vitamin supplemented women. Result: Hypervitaminemic levels of folate, biotin, pantothenate and riboflavin were found during any trimester of pregnancy due to vitamin supplementation. Despite the vitamin supplementation, a high percent of vitamin A, B6, niacin, thiamin and B12 hypovitaminemia was noted during pregnancy trimesters. An especially high percentage of niacin deficiency was seen during the 1st trimester; it worsened in later trimesters; B12 deficits increased during the late trimesters. Combination deficits of niacin, thiamin, vitamins A, B6, B12 were noted in each of the trimesters. Conclusions: Despite vitamin supplementation, a vitamin profile of pregnancy indicates that vitamin deficits exist during the trimesters. Also, combination hypovitaminemias of deficient vitamins were noted; this indicates that a vitamin deficit during pregnancy does not occur in isolation.

Water-soluble vitamins in cells and spent culture supernatants of Poteriochromonas stipitata, Euglena gracilis, and Tetrahymena thermophila

Vitamins B6 and B12, biotin, folates, riboflavin, nicotinate, pantothenate, biopterin, and vitamin C (l-ascorbate) were assayed in Poteriochromonas stipitata, Euglena gracilis, and Tetrahymena thermophila cells grown in defined media and in spent culture supernatants. P. stipitata and E. gracilis synthesized, stored and excreted folates (mainly as 5-methyltetrahydrofolate), B6, riboflavin, pantothenate, nicotinate, biopterin, and ascorbate. E. gracilis synthesized and stored biotin. T. thermophila did not synthesize the above vitamins except for B12, biopterin, and ascorbate; it excreted biopterin and stored B12 and ascorbate. Thiamin was left of consideration because all 3 organisms are thiamin auxotrophs. Possible ecological implications of these findings are considered.

Human plasma patterns during 14 days ingestion of vitamin E, beta-carotene, ascorbic acid, and their various combinations.

OBJECTIVE We wanted to learn about plasma patterns of ascorbic acid (AA), beta carotene (BC), and vitamin E (vit E) when each or their various combinations were fed to humans. Conceivably, the combined absorption of these antioxidants could synergize maximum plasma redox potential. METHODS Vit E (800 mg/day), BC (30 mg/day), and AA (1000 mg/day) were fed individually or in various combinations with each other to 91 volunteers divided into different feeding groups for 14 days. Plasma vit E, carotenes, and AA patterns were analyzed by standardized methods; values were compared with each groups baseline value. RESULTS AA feeding did not significantly increase already saturated plasma AA concentrations above baseline. Intake of BC did not influence vitamin A (vit A) levels. Feeding of only vit E or only BC, with or without AA addition, or a combination of BC and vit E significantly increased plasma vit E and carotene levels after 2 days. A statistically (ANOVA) significant increase in plasma vit E above baseline was noted when vit E was ingested combined with AA or BC; this increase in plasma vit E was not significant when AA, BC and vit E were taken in combination. CONCLUSION Our results show that BC or AA ingestion in combination with vit E significantly increases circulating vit E above that seen when vit E is individually ingested. Vit E in combination with BC or AA seems a practical means or increasing the circulating antioxidant potential afforded by vit E. Reasons why such synergism does not exist when an AA, BC, vit E combination is ingested is not yet obvious.

Interleukin-2 enhances biopterins and catecholamines production during adoptive immunotherapy for various cancers

Biopterins production during three different protocols for adoptive immunotherapy for human cancer was investigated. Adoptive immunotherapy treatment with interleukin‐2 (IL‐2) was carried out for 13 patients with malignant melanoma; eight with metastatic renal cell carcinoma; and three with metastatic colon cancer. The authors estimated total biopterins in plasma and lymphokine (IL‐2)‐activated killer cells (LAK) from these patients before and during various treatment phases to determine if increased biopterins production reflects leukocyte activation by IL‐2 or antitumor activity. They noted an increased synthesis of total “biopterins,” i.e., biopterin; 7,8‐dehydrobiopterin; and L‐neopterin, in LAK cells and plasma which correlated with IL‐2 exposure. Mean plasma biopterins were normal (1.2 ± 0.5 ng/ml) before therapy; in contrast, biopterins increased significantly to 3.4 ± 1.9 ng/ml and 3.9 ± 1.9 ng/ml during IL‐2 and IL‐2 + LAK treatment each, respectively. Similar biopterin elevations were noted irrespective of the different adoptive immunotherapy protocols used. Elevated biopterins decreased to normal levels (1.2 ± 0.7 ng/ml) when IL‐2 treatment was omitted. Tumor regression with adoptive immunotherapy did not correlate with increased plasma biopterins. Increased biopterins production was also associated with increase in plasma catecholamine after IL‐2 treatment during adoptive immunotherapy. Conceivably increased biopterins, induced by IL‐2 activation of a leukocyte population, is a cell‐mediated consequence not necessarily serving as a signal for the antitumor effect associated with adoptive immunotherapy.

Determination of metabolically active B12 and inactive B12 analog titers in human blood using several microbial reagents and a radiodilution assay.

Metabolically active B12 analogs and inactive B12 analogs were measured in plasma, red blood cells (RBC), and pooled pernicious anemia serum. B12 values by Lactobacillus leichmannii, Escherichia coli, Euglena gracilis, and radioisotope dilution method (RIDA) as assays for total B12 (active analogs + inactive analogs) were compared to Ochromonas malhamensis values as index of only metabolically active B12. B12 values above those with O malhamensis distinguished inactive analogs from active B12. Inactive analogs contribute 85, 97, 135, and 163% above active B12 activity in normal plasma when E gracilis, L leichmannii, RIDA, and E coli, respectively, were used for B12 analysis. RIDA B12 determinations for active B12 in plasma showed that 44% of the B12 measured was still due to inactive analogs when compared to O malhamensis B12 activity. Inactive B12 analogs contributed 21, 151, and 224% above O malhamensis active B12 in RBC when E gracilis, L leichmannii, and E coli, respectively, were used.