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Background/Objectives: Nitric oxide (NO) has been proposed as a mediator of vascular expansion during pregnancy. Inability to increase NO synthesis and/or production of its precursor, arginine, may be a contributor to pregnancy-induced hypertension or preeclampsia. Because maternal weight is associated with blood pressure and risk of preeclampsia during pregnancy, it may also influence arginine and/or NO production. The purpose of this study was to determine the in vivo arginine production and NO synthesis rate in pregnant women with normal (n=10) and low (n=10) body mass indices (BMIS). Subjects/Methods: Arginine flux and NO synthesis rate were measured in the postabsorptive state with constant infusions of [sup.15][N.sub.2]-arginine and [sup.13]C, [sup.2.H.sub.4]-citrulline. Plasma concentrations of arginine and NO metabolites were also measured. Kinetic parameters were correlated to maternal variables, gestational age, birth weight and blood pressure. Results: Endogenous arginine flux was significantly faster in the low-BMI compared with normal-BMI women in the first trimester (63.1 [+ or -] 3.4 vs 50.2 [+ or -] 2.0[[micro]mol/kg per h, P Conclusions: These findings suggest, but do not prove, that maternal BMI may be a factor in the ability to produce NO during pregnancy and may be one way by which BMI influences blood pressure during pregnancy. doi:10.1038/ejcn.2009.24; published online 13 May 2009 Keywords: arginine production; nitric oxide synthesis; maternal weight; maternal body mass index, Introduction A physiological adaptation of pregnancy is expansion of the maternal vascular compartment. It starts with vasodilatation as peripheral resistance falls by 6 weeks and reaches a minimum in mid-pregnancy [...]

The objectives for this experiment were to determine the effect of the callipyge phenotype on protein kinetics. We studied callipyge and normal lambs (n = 37) at 5, 8, and 11 wk of age (n = 4 to 7/ group) to determine how protein kinetics are altered by this trait. Total protein, DNA, and RNA and calpastatin activity were measured in five skeletal muscles and in the heart, kidneys, and liver, and protein accretion rates were calculated. At 8 wk, the fractional synthesis rates of proteins in these tissues were measured in vivo using a primed, continuous 8-h infusion of [(super 2)H(sub 5)]-phenylalanine. Fractional rates of protein degradation were estimated by differences. At 5 wk of age, muscle weights, protein mass, protein:DNA, RNA:DNA, and calpastatin activity were higher (P < .05) for callipyge, and protein mass differences continued to increase through 11 wk. At 8 wk, fractional rates of protein synthesis and degradation were lower (P < .05) in callipyge than in normal lambs. The organs of callipyge lambs exhibited reduced growth at 11 wk. Thus, enhanced muscle growth seems to be maintained in callipyge lambs by reduced protein degradation rather than increased protein synthesis. However, we cannot exclude the possibility that the initial onset of the callipyge condition may be caused by an increase in the fractional rate of protein synthesis. Key Words: Calpastatin, Fiber, Sheep, Protein Synthesis, Protein Degradation

The contributions of dietary nucleotides and nucleotides synthesized de novo to ribonucleic acid synthesis in vivo were estimated by feeding, from d 13 to 18 of gestation, two groups of five pregnant mice a defined diet that contained either uniformly [[U.sup.13]C]-labeled nucleotides or [[U.sup.13]C]-algal amino acids isolated from algal biomass. Ribonucleic acid and protein were isolated from mucosa, liver and fetus. Nucleosides and amino acids were isolated and converted to their trimethylsilyl and n-propyl ester, heptaflurobutyramide derivatives, respectively. The isotopic enrichments of all isotopomers were determined by gas chromatography-mass spectrometry. In the mice that ingested [[U.sup.13]C]-nucleotides, the isotopic enrichment of [[U.sup.13]C]-purines (0.03-0.2 mol/100 mol) was significantly (P < 0.001) less than that of [[U.sup.13]C]-uridine (1.5-4.2 mol/100 mol). [13[C.sub.5]]-Purines (0.1-0.8 mol/100 mol) and [13[C.sub.4]]-uridine (0.2-0.5 mol/100 mol) were detected, showing that some dietary bases and ribose were incorporated via the salvage pathway. In mice that ingested [U.sup.13]C-amino acids, the isotopic enrichment (2-4.6 mol/100 mol) of the [13[C.sub.2]]-purines, which derive from [[U.sup.13]C]-glycine, was between 73 (liver) and 113% (fetus) of protein-bound 13[C.sub.2]-glycine. The isotopic enrichment (0.8-1.6 mol/100 mol) of [13[C.sub.3]]-uridine, an isotopomer that derives from [[U.sup.13]C]-aspartate, was 50 (liver) to 126% (mucosa) of [13[C.sub.4]]-protein-bound aspartate. The results suggest that a large majority of the bases incorporated into maternal and fetal ribonucleic acids derive from synthesis de novo. INDEXING KEY WORDS: mice; nucleic acids; uniformly labeled tracers; purine synthesis; pyrimidine synthesis

Plasma glutamine levels decrease in association with severe injury, which suggests that the consumption of glutamine exceeds the production of glutamine or possibly represents a deficit in the release of [...]

Starch is the major source of food glucose and its digestion requires small intestinal alpha-glucosidic activities provided by the 2 soluble amylases and 4 enzymes bound to the mucosal surface of enterocytes. Two of these mucosal activities are associated with sucrase-isomaltase complex, while another 2 are named maltase-glucoamylase (Mgam) in mice. Because the role of Mgam in alpha-glucogenic digestion of starch is not well understood, the Mgam gene was ablated in mice to determine its role in the digestion of diets with a high content of normal corn starch (CS) and resulting glucose homeostasis. Four days of unrestricted ingestion of CS increased intestinal alpha-glucosidic activities in wild-type (WT) mice but did not affect the activities of Mgam-null mice. The blood glucose responses to CS ingestion did not differ between null and WT mice; however, insulinemic responses elicited in WT mice by CS consumption were undetectable in null mice. Studies of the metabolic route followed by glucose derived from intestinal digestion of (13)C-labeled and amylase-predigested algal starch performed by gastric infusion showed that, in null mice, the capacity for starch digestion and its contribution to blood glucose was reduced by 40% compared with WT mice. The reduced alpha-glucogenesis of null mice was most probably compensated for by increased hepatic gluconeogenesis, maintaining prandial glucose concentration and total flux at levels comparable to those of WT mice. In conclusion, mucosal alpha-glucogenic activity of Mgam plays a crucial role in the regulation of prandial glucose homeostasis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although the reduction in whole-body protein turnover and net protein loss induced by protein-energy malnutrition (PEM) has been well documented, it is unclear whether the protein-sparing mechanisms elicited by chronically inadequate intakes of dietary protein and energy are affected by the protein catabolic response to infection. OBJECTIVE: The objective of this study was to determine whether the presence of infection alters the PEM-induced reduction in whole-body protein metabolism. DESIGN: We determined whole-body leucine kinetics in 4 boys and 3 girls aged 6-15 mo with edematous PEM and infection approximately 3 d after admission (study 1), when they were both infected and malnourished; approximately 11 d after admission (study 2), when infection had resolved but they were still anthropometrically malnourished; and at recovery (study 3), when weight-for-length was at least 90% of that expected. RESULTS: The children had significantly less leucine flux in both study 1 and study 2 than they had in study 3. There were no significant differences in the amount of leucine released from protein breakdown or used for protein synthesis between study 1 and study 2. There were no significant differences in leucine balance or in either the amount or percentage of enteral leucine extracted by the splanchnic tissues among the 3 studies. CONCLUSIONS: When subjects are in the fed state, severe PEM induces a marked reduction in whole-body protein synthesis and breakdown rates, and the presence of infection does not alter this adaptation and hence the overall protein balance. A corollary is that children with severe PEM do not mount a protein catabolic response to infection. Copyright © 2002 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

In disadvantaged populations, recurrent infections lead to a loss of body nitrogen and worsen nutritional status. The resulting malnutrition, in its turn, produces a greater susceptibility to infection. This study aimed to examine the ability of a new minimally invasive tracer protocol to measure leucine oxidation, and then to use it to quantify the effect of vaccination on leucine kinetics and oxidation. Undernourished men (n = 5; body mass index 16.3 +/- 0.9 kg/m(2)) and children (n = 9; age 4.1 +/- 0.6 y; weight-for-age Z-score -2.3 +/- 0.7) underwent metabolic studies 6 d before and 1 d after vaccination with diphtheria, pertussis and tetanus (DPT). The tracer protocol was performed in the fed state and involved two 3-h sequential periods of frequent (20 min) oral doses of NaH(13)CO(3) or [1-(13)C] leucine. Frequent breath samples and urine collections were made. Blood samples were obtained from the men and used for the determination of the isotopic enrichment of alpha-ketoisocaproic acid. The prevaccination oxidation of leucine (percentage of dose +/- SD) was 18.1 +/- 2.3 (men) and 16.7 +/- 3.8 (children). One day after vaccination, these values had risen to 19. 9 +/- 1.9 (P < 0.05) in the men and to 19.5 +/- 4.6 (P < 0.01) in the children. In the adults, vaccination was associated with a rise in whole-body protein breakdown [mg protein/(kg.h)] from 200 +/- 40 to 240 +/- 10 (P < 0.05). A minor simulated infection increases leucine catabolism in undernourished humans and this new, minimally invasive protocol is sufficiently sensitive to measure these changes. [ABSTRACT FROM AUTHOR]

Reports developments related to AIDS virology as of August 1999. Effect of nitric oxide on the regulation of nuclear factor; Exclusion of HIV coreceptors CXCR4, CCR5 and CCR3 from the HIV envelope; Significance of sterilization of HIV with irradiation in the infected bone allografts.

The changes in protein metabolism of severe childhood malnutrition are generally perceived as a metabolic adaptation to chronic protein undernutrition. However, severe malnutrition is invariably accompanied by infections which also have profound effects on protein metabolism. This study aimed to distinguish the effect of protein undernutrition from that of an inflammatory stimulus on muscle and plasma protein synthesis rates. Two groups of five piglets consumed diets containing either 23% or 3% protein for 4 wk. They then were infused intravenously with 2H3-leucine before and 48 h after subcutaneous injections of turpentine to measure the fractional synthesis rates (FSR) of muscle protein and both the FSR and the absolute synthesis rates (ASR) of albumin and fibrinogen. Prior to turpentine injection, compared to control piglets, protein-deficient piglets had significantly lower muscle FSR and plasma concentrations of both albumin and fibrinogen, although only albumin had lower FSR and ASR. Turpentine injection decreased muscle FSR but increased the FSR, ASR and plasma concentrations of both albumin and fibrinogen in control piglets. In protein-deficient piglets, the inflammatory stress caused a further decrease in muscle protein FSR and in plasma albumin concentration despite marked increases in albumin FSR and ASR. Fibrinogen FSR, ASR and plasma concentration were increased. We conclude that protein undernutrition and inflammation elicit the same kinetic response in muscle protein but different kinetic responses in plasma proteins. Furthermore, whereas protein deficiency reduces the plasma albumin pool via a reduction in albumin synthesis, inflammation reduces it through a stimulation of catabolism and/or loss from the intravascular space. [ABSTRACT FROM AUTHOR]

The use of plasma protein concentrations to assess protein-nutritional status has been questioned because concentrations and kinetics are affected by factors other than protein intake. To determine the effect of protein deficiency on plasma protein concentration and synthesis, two groups of four piglets consumed diets containing either 20 or 3% protein. After 8 wk, 2H3-leucine was infused intravenously to measure the fractional and absolute synthesis rates (FSR and ASR) of albumin, transferrin, retinol binding protein (RBP), transthyretin (TTR), a new peptide called TTR2, the high density apolipoprotein (HDL-apoA-1), fibrinogen, and haptoglobin. Compared with controls, protein-deficient pigs had significantly lower (P < 0.05) plasma albumin, RBP and TTR2 concentrations, significantly slower (P < 0.05) FSR of fibrinogen, HDL-apoA-1, transferring and TTR2, significantly lower (P < 0.05) ASR of albumin, fibrinogen, transferrin, and TTR2, and a significantly higher (P < 0.05) ASR of TTR. Fibrinogen and transferrin concentrations did not differ between groups, but transthyretin concentration was higher in protein-deficient pigs. These results suggest that protein-nutritional status cannot be predicted from the concentrations of all plasma proteins, that chronic protein deficiency affects the rate of synthesis of only some plasma proteins, and that the kinetic response of plasma proteins to protein restriction cannot be predicted from measurements of plasma concentrations. [ABSTRACT FROM AUTHOR]

To investigate the utilization of dietary amino acids for hepatic protein synthesis, seven female pigs ( 28 d old, 7.5 kg) were implanted with catheters in a carotid artery, the jugular and portal veins, and the stomach. A portal flow probe was also implanted. The pigs were fed a high protein diet once hourly and infused intragastrically with [U-13C]algal protein for 6 h. Amino acid labeling was measured in arterial and portal blood, in the hepatic free and protein-bound pools and in apolipoprotein B-100 (apoB-100), albumin and fibrinogen. The isotopic enrichments of apoB-100-bound [U-13C]threonine, leucine, lysine and phenylalanine were 33, 100, 194 and 230% higher than those of their respective hepatic free amino acid pools (P < 0.01). Using the labeling of apoB-100 to estimate that of the protein synthetic precursor, the fractional rate of hepatic protein synthesis was 42 +/- 2%/d. Between 5 and 8% of the dietary tracer amino acids was used for hepatic protein synthesis. In contrast to the small intestinal mucosa, in which the majority of the metabolized amino acids were apparently catabolized, protein synthesis utilized from 48% (threonine) to 90% (lysine) of the hepatic uptake of tracer amino acids. It appears that hepatic protein synthesis consumes nutritionally significant quantities of dietary essential amino acids in first pass and that extracellular, especially portal, essential amino acids are channeled to hepatic protein synthesis in the fed state. [ABSTRACT FROM AUTHOR]

To investigate the contribution of dietary carbohydrate to glutamate and acetyl CoA synthesis, two groups of adult mice were fed a high- (HCD) or a low-carbohydrate diet (LCD) in which 5% of the carbohydrate was [U-13C]-glucose. Four animals from each dietary group were killed after 1, 2 and 5 d. The tracer:tracee ratios of [13C3] and [13C6]blood glucose and of the [13C2] and [13C3] isotopomers of blood, mucosal, hepatic and muscle alanine and glutamate were used to calculate the fractional contribution of glucose to the 3-carbon, acetyl CoA and oxaloacetate pools of each tissue. In the HCD mice, glucose contributed 66, 33 and 31% of the acetyl CoA pool of muscle, liver and mucosa, respectively. The contribution of glucose to acetyl CoA was lowered by 33% (P < 0.05) and 55% (P < 0.01) in the liver and muscle of the LCD group, respectively, but was unaltered in the mucosa. Glucose made a minor contribution to glutamate synthesis via oxaloacetate in the liver (23%) and muscle (10%) of the HCD group. The fraction of hepatic and muscle glutamate synthesis derived from glucose was not affected by the diet. We conclude that glucose oxidation in liver and muscle parallels the contribution of carbohydrate to dietary energy and that glucose is not a major carbon precursor for muscle glutamate synthesis. Net glutamate synthesis in extraintestinal tissues is preserved when dietary carbohydrate is restricted. [ABSTRACT FROM AUTHOR]

To investigate the extent of first-pass intestinal metabolism of dietary amino acids, seven female pigs (28 d old, 8.0 kg) were implanted with arterial, venous, portal and gastric catheters and with an ultrasonic portal blood flow probe. The pigs were fed a milk-based diet once hourly and infused intragastrically with [U-13C]algal protein. On average, 56% of the essential amino acid (EAA) intake appeared in the portal blood. However, the net portal balance of methionine (48% of intake) and threonine (38% of intake) tended (P = 0.08) to be lower than the mean of all EAA. The net portal balance (expressed as a percentage of intake) of alanine (205%), tyrosine (167%) and arginine (137%) exceeded their intake. Net portal outflow of ammonia accounted for 18% of total amino acid nitrogen intake. As a percentage of the enteral tracer input, there was substantial first-pass metabolism of lysine (35%), leucine (32%), phenylalanine (35%) and threonine (61%). However, only 18, 21, 18 and 12% of the total first-pass metabolism of lysine, leucine, phenylalanine and threonine, respectively, were recovered in mucosal protein. We conclude that roughly one third of dietary intake of EAA is consumed in first-pass metabolism by the intestine and that amino acid catabolism by the mucosal cells is quantitatively greater than amino acid incorporation into mucosal protein. [ABSTRACT FROM AUTHOR]