Effect of multi-nutrient insufficiency on markers of one carbon metabolism in young women: response to a methionine load.

BACKGROUND/OBJECTIVES: Multi-nutrient insufficiencies as a consequence of nutritional and economic factors are common in India and other developing countries. We have examined the impact of multi-nutrient insufficiency on markers of one carbon (1C) metabolism in the blood, and response to a methionine load in clinically healthy young women. SUBJECTS/METHODS: Young women from Pune, India (n=10) and Cleveland, USA (n=13) were studied. Blood samples were obtained in the basal state and following an oral methionine load (50 mg/kg of body weight in orange juice). Plasma concentrations of vitamin B12, folate and B6 were measured in the basal state. The effect of methionine load on the levels of methionine, total homocysteine, cysteine, glutathione and amino acids was examined. RESULTS: Indian women were significantly shorter and lighter compared with the American women and had lower plasma concentration of vitamins B12, folate and B6, essential amino acids and glutathione, but higher concentration of total homocysteine. The homocysteine response to methionine load was higher in Indian women. The plasma concentrations of glycine and serine increased in the Indian women after methionine (in juice) load. A significant negative correlation between plasma B6 and homocysteine (r= -0.70), and plasma folate and glycine and serine levels were observed in the Indian group (P<0.05) but not in the American group. CONCLUSIONS: Multi-nutrient insufficiency in the Indian women caused unique changes in markers of whole body protein and 1C metabolism. These data would be useful in developing nutrient intervention strategies.

Estimation of gluconeogenesis in newborn infants.

The rate of glucose turnover (R(a)) and gluconeogenesis (GNG) via pyruvate were quantified in seven full-term healthy babies between 24 and 48 h after birth and in twelve low-birth-weight infants on days 3 and 4 by use of [(13)C(6)]glucose and (2)H(2)O. The preterm babies were receiving parenteral alimentation of either glucose or glucose plus amino acid with or without lipids. The contribution of GNG to glucose production was measured by the appearance of (2)H on C-6 of glucose. Glucose R(a) in full-term babies was 30 +/- 1.7 (SD) micromol. kg(-1). min(-1). GNG via pyruvate contributed approximately 31% to glucose R(a). In preterm babies, the contribution of GNG to endogenous glucose R(a) was variable (range 6-60%). The highest contribution was in infants receiving low rates of exogenous glucose infusion. In an additional group of infants of normal and diabetic mothers, lactate turnover and its incorporation into glucose were measured within 4-24 h of birth by use of [(13)C(3)]lactate tracer. The rate of lactate turnover was 38 micromol. kg(-1). min(-1), and lactate C, not corrected for loss of tracer in the tricarboxylic acid cycle, contributed approximately 18% to glucose C. Lactate and glucose kinetics were similar in infants that were small for their gestational age and in normal infants or infants of diabetic mothers. These data show that gluconeogenesis is evident soon after birth in the newborn infant and that, even after a brief fast (5 h), GNG via pyruvate makes a significant contribution to glucose production in healthy full-term infants. These data may have important implications for the nutritional support of the healthy and sick newborn infant.

Relation between transamination of branched-chain amino acids and urea synthesis: evidence from human pregnancy.

Protein and nitrogen (N) accretion by the mother is a major adaptive response to pregnancy in humans and animals to meet the demands of the growing conceptus. Quantitative changes in whole body N metabolism were examined during normal pregnancy by measuring the rates of leucine N (QN) and carbon (QC) kinetics with the use of [1-13C,15N]leucine. Rate of synthesis of urea was measured by [15N2]urea tracer. Pregnancy-related change in total body water was quantified by H2[18O] dilution, and respiratory calorimetry was performed to quantify substrate oxidation. A significant decrease in the rate of urea synthesis was evident in the 1st trimester (nonpregnant 4.69 +/- 1.14 vs. pregnant 3.44 +/- 1.11 micromol . kg-1 . min-1; means +/- SD, P < 0.05). The lower rate of urea synthesis was sustained through the 2nd and 3rd trimesters. QN was also lower in the 1st trimester during fasting; however, it reached a significant level only in the 3rd trimester (nonpregnant 166 +/- 35 vs. 3rd trimester 135 +/- 16 micromol . kg-1 . h-1; P < 0.05). There was no significant change in QC during pregnancy. A significant decrease in the rate of transamination of leucine was evident in the 3rd trimester both during fasting and in response to nutrient administration (P < 0.05). The rate of deamination of leucine was correlated with the rate of urea synthesis during fasting (r = 0.59, P = 0.001) and during feeding (r = 0.407, P = 0. 01). These data show that pregnancy-related adaptations in maternal N metabolism are evident early in gestation before any significant increase in fetal N accretion. It is speculated that the lower transamination of branched-chain amino acids may be due to decreased availability of N acceptors such as alpha-ketoglutarate as a consequence of resistance to insulin action evident in pregnancy.

Glucose turnover and gluconeogenesis in human pregnancy.

The rate of appearance (Ra) of glucose in plasma and the contribution of gluconeogenesis were quantified in normal pregnant women early ( approximately 10 wk) and late ( approximately 34 wk) in gestation. Their data were compared with those of normal nonpregnant women. Glucose Ra was measured using the [U-13C]glucose tracer dilution method. Gluconeogenesis was quantified by the appearance of 2H on carbon 5 and 6 of glucose after deuterium labeling of body water pool. Weight-specific glucose Ra was unchanged during pregnancy (nonpregnant, 1.89+/-0.24; first trimester, 2.05+/-0.21; and third trimester 2.17+/-0.28 mg/kg.min, mean+/-SD), while total glucose Ra was significantly increased (early, 133.5+/-7.2; late, 162.6+/-16.4 mg/min; P = 0.005). The fractional contribution of gluconeogenesis via pyruvate measured by 2H enrichment on C-6 of glucose (45-61%), and of total gluconeogenesis quantified from 2H enrichment on C-5 of glucose (i.e. , including glycerol [68-85%]) was not significantly different between pregnant and nonpregnant women. Inasmuch as total glucose Ra was significantly increased, total gluconeogenesis was also increased in pregnancy (early pregnancy, 94.7+/-15.9 mg/min; late pregnancy, 122.7+/-9.3 mg/min; P = 0.003). These data demonstrate the ability of the mother to adapt to the increasing fetal demands for glucose with advancing gestation. The mechanism for this unique quantitative adjustment to the fetal demands remains undefined.

[Impact of a quality approach for transfusion safety on prescription, circuit optimization, traceability]. / Impact d'une démarche qualité en sécurité transfusionnelle sur la prescription, l'optimisation des circuits, la traçabilité. Expérience du CHRU de Lille.

The Quality Assessment Program undertaken at the Regional University Hospital of Lille benefits from previous experience making management of this project possible: continuing education, preliminary initiation into the quality approach, and existing reference systems. The aims are to master the rates of outdated and no longer efficient red cell concentrates, to control red cell concentrate delivery time, to validate the refrigeration line integrity and to ensure a flawless marking out process. The process studied is transverse, with those taking part in it belonging to several professional categories. The method will consist in a process identification, its description and characterization according to FMECA (Failure Mode Effects and Criticality Analysis), the creation of a new process and its improvement. Thus failures should be identified and classified hierachically. The corrective actions will consist in communication aids, an education program, blood product transport and blood depot reorganization, data processing improvement and medical equipment acquisition. Quality indicators are developed according to the objectives of the study, and progress indicators are developed as a periodical assessment of blood transfusion practice. This ambitious project relies on the involvement of Hospital Management and referent network. These referents facilitate the improvement processes for those taking part in this process.

[Severe form of neonatal hemolytic disease by anti-Vel allo-immunization]. / Forme sévère de maladie hémolytique néonatale par allo-immunisation anti-Vel.

BACKGROUND: Routine detection of maternal sensitization during pregnancy sometimes reveals alloimmunization by exceptional antigens. CASE REPORT: A first pregnancy was complicated by a severe post-partum anemia in the mother, that required a blood transfusion. Irregular agglutinins were detected during the first trimester of a second pregnancy, for which the father was different from the first. The specific antibody was not identified at that time. The newborn, born at a gestational age of 39 weeks, developed severe jaundice at 3 hours of life, with hemolytic disease, anemia and hepatomegaly. Therapy included two transfusions of packed, washed red cells obtained from the mother on days 7 and 25. Immunologic tests showed that the hemolytic disease of this newborn was due to an anti-Vel alloimmunization. CONCLUSION: Antibodies detected during the pregnancy must be identified in order to manage properly any perinatal problems due to rare antibodies.