Individual Plasma Amino Acids Research Articles

Early versus late parenteral nutrition in term and late preterm infants: study protocol for a randomised controlled trial

BackgroundDespite the wide use of parenteral nutrition (PN) in neonatal intensive care units (NICU), there is limited evidence regarding the optimal time to commence PN in term and late preterm infants. The recommendations from the recently published ESPGHAN/ESPEN/ESPR/CPEN and NICE guidelines are substantially different in this area, and surveys have reported variations in clinical practice. The aim of this randomised controlled trial (RCT) is to evaluate the benefits and risks of early versus late PN in term and late preterm infants.Methods/designThis study is a single-centre, non-blinded RCT in the NICU of Perth Children’s Hospital, Western Australia.A total of 60 infants born ≥34 weeks of gestation who have a high likelihood of intolerance to enteral nutrition (EN) for at least 3-5 days will be randomised to early (day 1 or day 2 of admission) or late commencement (day 6 of admission) of PN after informed parental consent. In both groups, EN will be commenced as early as clinically feasible. Primary outcomes are plasma phenylalanine and plasma F2-isoprostane levels on Day 4 and Day 8 of admission. Secondary outcomes are total and individual plasma amino acid profiles, plasma and red blood cell fatty acid profiles, in-hospital all-cause mortality, hospital-acquired infections, length of hospital/NICU stay, z scores and changes in z scores at discharge for weight, height and head circumference, time to full EN, duration of respiratory (mechanical, non-invasive) support, duration of inotropic support, the incidence of hyper and hypoglycaemia, incidence of metabolic acidosis, liver function, blood urea nitrogen, and C-reactive protein (CRP).DiscussionThis RCT will examine the effects of early versus late PN in term and late preterm infants by comparing key biochemical and clinical outcomes and has the potential to identify underlying pathways for beneficial or harmful effects related to the timing of commencement of PN in such infants.Trial registrationANZCTR; ACTRN12620000324910 (3rd March 2020)

Four weeks treatment with the GLP-1 receptor analogue liraglutide lowers liver fat and concomitantly circulating glucagon in individuals with overweight.

We investigated the effect of pharmacologically induced weight loss on markers of glucagon resistance in individuals with overweight during treatment with the glucagon-like peptide-1 receptor agonist liraglutide. We performed an open-label study in 14 men with overweight (age 38 ± 11 years, BMI 32 ± 4 kg/m2) without simultaneously diabetes. Subjects were treated with liraglutide, initiated and titrated with 0.6 mg/day/week to reach the final dose of 3.0 mg/day. Subjects were examined at baseline, during titration (Week 4), after 2 weeks of steady state (Week 6) of final dosing of liraglutide and 3 weeks after discontinuation of liraglutide (follow-up). Study participants lost 3.3 ± 1.9 kg (3%) total body weight during the first 4 weeks of treatment with liraglutide. Simultaneously, liver fat content decreased from 12.4 ± 11.6% to 10.2 ± 11.1%, p = 0.025, whereas fat content in the spleen and subcutaneous tissue was unaltered. Markers of glucagon resistance, including plasma glucagon and the glucagon-alanine-index, also decreased significantly during treatment, but total and individual plasma amino acid concentrations did not. Insulin resistance (HOMA-IR) was unchanged during treatment, whereas insulin clearance increased. Treatment with the GLP-1 receptor analogue liraglutide decreased liver fat content, and simultaneously attenuated glucagon concentrations and the glucagon-alanine index in individuals with overweight without diabetes.

Glucagon acutely regulates hepatic amino acid catabolism and the effect may be disturbed by steatosis

ObjectiveGlucagon is well known to regulate blood glucose but may be equally important for amino acid metabolism. Plasma levels of amino acids are regulated by glucagon-dependent mechanism(s), while amino acids stimulate glucagon secretion from alpha cells, completing the recently described liver-alpha cell axis. The mechanisms underlying the cycle and the possible impact of hepatic steatosis are unclear. MethodsWe assessed amino acid clearance in vivo in mice treated with a glucagon receptor antagonist (GRA), transgenic mice with 95% reduction in alpha cells, and mice with hepatic steatosis. In addition, we evaluated urea formation in primary hepatocytes from ob/ob mice and humans, and we studied acute metabolic effects of glucagon in perfused rat livers. We also performed RNA sequencing on livers from glucagon receptor knock-out mice and mice with hepatic steatosis. Finally, we measured individual plasma amino acids and glucagon in healthy controls and in two independent cohorts of patients with biopsy-verified non-alcoholic fatty liver disease (NAFLD). ResultsAmino acid clearance was reduced in mice treated with GRA and mice lacking endogenous glucagon (loss of alpha cells) concomitantly with reduced production of urea. Glucagon administration markedly changed the secretion of rat liver metabolites and within minutes increased urea formation in mice, in perfused rat liver, and in primary human hepatocytes. Transcriptomic analyses revealed that three genes responsible for amino acid catabolism (Cps1, Slc7a2, and Slc38a2) were downregulated both in mice with hepatic steatosis and in mice with deletion of the glucagon receptor. Cultured ob/ob hepatocytes produced less urea upon stimulation with mixed amino acids, and amino acid clearance was lower in mice with hepatic steatosis. Glucagon-induced ureagenesis was impaired in perfused rat livers with hepatic steatosis. Patients with NAFLD had hyperglucagonemia and increased levels of glucagonotropic amino acids, including alanine in particular. Both glucagon and alanine levels were reduced after diet-induced reduction in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR, a marker of hepatic steatosis). ConclusionsGlucagon regulates amino acid metabolism both non-transcriptionally and transcriptionally. Hepatic steatosis may impair glucagon-dependent enhancement of amino acid catabolism.

Mitochondrial respiratory chain disease discrimination by retrospective cohort analysis of blood metabolites

Diagnosing primary mitochondrial respiratory chain (RC) dysfunction has long relied on invasive tissue biopsies, since no blood-based biomarker has been shown to have sufficiently high sensitivity and specificity across the myriad of individual clinical presentations. We sought to determine whether cohort-level evaluation of commonly obtained blood analytes might reveal consistent patterns to discriminate a heterogenous group of primary mitochondrial RC disease subjects both from control individuals and from subjects with pyruvate dehydrogenase deficiency. MethodsFollowing IRB approval, 62 biochemical analyte concentrations or ratios were retrospectively analyzed in three well-defined and intentionally heterogeneous subject cohorts reflective of clinical practice: [1] Primary mitochondrial disease (n=19); [2] pyruvate dehydrogenase deficiency (n=4); and [3] controls (n=27). Blood analyte categories included comprehensive chemistry profile, creatine kinase, lipoprotein profile, lactate, pyruvate, and plasma amino acid profile. Non-parametric analyses were used to compare the median of each analyte level between cohorts. ResultsDisease cohorts differed significantly in their median levels of triglycerides, lactate, pyruvate, and multiple individual plasma amino acids. Primary mitochondrial disease was significantly discriminated at the cohort level from pyruvate dehydrogenase deficiency by greater pyruvate and alanine elevation in pyruvate dehydrogenase deficiency, as well as significantly increased branched chain amino acid (BCAA) levels and increased ratios of individual BCAAs to glutamate in mitochondrial disease. In addition, significant elevation of median blood triglyceride level was seen in the primary mitochondrial disease cohort. ConclusionsBlood metabolite profile analysis can discriminate a heterogeneous cohort of primary mitochondrial disease both from controls and from pyruvate dehydrogenase deficiency. Elevated BCAA levels, either absolutely or when considered relative to the level of glutamate, are common metabolic sequelae of primary mitochondrial RC disease. Prospective study is needed to validate observed plasma metabolite alterations as a potential biomarker of disease both in larger cohorts and at the individual subject level.

Hyperalimentation results in paradoxical fall in tyrosine levels in very preterm infants receiving parenteral nutrition: Abstract G72 Table 1

<h3>Background</h3> Hyperalimentation describes the increase in glucose, amino acid and lipid intake designed to overcome postnatal growth failure in preterm infants. Preterm infants are dependent on phenylalanine metabolism to maintain tyrosine levels because of tyrosine concentration limits in parenteral nutrition (PN). Phenylalanine hydroxylase activity is increased by increasing phenylalanine intake (preterm infants), steroids and diabetes (animal models). The latter is reversed by insulin administration. Hyperalimentation increases hyperglycaemia requiring insulin treatment1. <h3>Aim</h3> To compare the plasma amino acid profiles in preterm infants receiving a hyperalimentation versus a control PN regimen. <h3>Methods</h3> Infants &lt;29 weeks gestation were randomised to receive hyperalimentation (25% more glucose, 4 g/kg/day versus 3 g/kg/day protein/lipid) or a control regimen within 5 days of birth with head growth as the primary outcome1. Metabolic markers of PN “intolerance” including hyperglycaemia, insulin use, urea and amino acid profiles and hyperlipidaemia were collected from routine laboratory testing and the electronic patient database. Amino acid levels were measured on day 9 (ion exchange chromatography). <h3>Results</h3> 142 infants were randomised with 118 amino acid profiles obtained on day 8-10. There were no differences in birthweight or gestation between groups. Of the 22 individual plasma amino acid levels, 14 showed a rise (p&lt;0.05) and 7 no change (p&gt;0.05) when comparing hyperalimentation (n=57) with controls (n=61). Median (IQR) phenylalanine levels increased from 72 (63-79) mmol/l to 80 (65-89) mmol/l (p=0.03). Only tyrosine levels fell (p&lt;0.01) with hyperalimentation resulting in suboptimal tyrosine levels (normal range 33-75 mmol/l). This was associated with the increase in insulin-treated hyperglycaemia seen in this group (table 1; all insulin versus no insulin comparisons: p&lt;0.001). <h3>Conclusion</h3> Hyperalimentation results in a paradoxical fall in plasma tyrosine levels associated with an increase in insulin-treated hyperglycaemia. We propose that insulin administration inhibits phenylalanine hydroxylase activity preventing the PN dependent preterm infant maintaining adequate tyrosine levels.

Amino acid metabolism during endotoxemia in fed pigs

Individual plasma amino acid (AA) changes were quantified in endotoxemic fed pigs to calculate their catabolic and appearance rates. Pigs (19.1 ± 0.4 kg BW) were surgically fitted with an indwelling jugular catheter, allowed to recover, food‐deprived overnight, fed (t = −2 h), and treated with either sterile saline (n=16) or 10 μg/kg BW of LPS (n=15) at t = 0 h. Multiple blood samples were collected from −2 to 24 h after LPS treatment. Area under the curve (AUC) was calculated for individual AA from t = − 2 h to the first time when concentrations were equivalent for saline and LPS treatments, and from there to 24 h. Initially Lys, Met, Phe, His, Arg, and Thr AUC were less (P&lt;0.03) in LPS pigs compared to saline. Then, Lys, Met, and Phe AUC in LPS pigs exceeded (P&lt;0.01), His tended to be higher (P=0.07), but Arg and Thr were not different (P=0.13) from saline controls. For the entire study, AUC for Ile, Leu, Val, Gln, Orn, Trp, and Tyr in LPS pigs were reduced (P&lt;0.04) while Ala and Tau (P&lt;0.001) were greater in LPS pigs compared to controls. Initially, Glu AUC was not different (P=0.91) but subsequently became reduced (P&lt;0.01) in LPS pigs compared to saline controls. In LPS pigs, calculated AA catabolism ranged from −0.04 to −1.34 μmole·kg BW−1·h−1 and plasma appearance ranged from +0.03 to +0.74 μmole·kg BW−1·h−1. Our results support the need for AA supplementation of critically ill patients. College of Agriculture and Life Sciences

Plasma Amino Acid Concentrations During Late Rehabilitation in Patients With Traumatic Brain Injury

Børsheim E, Bui Q-UT, Wolfe RR. Plasma amino acid concentrations during late rehabilitation in patients with traumatic brain injury. Objectives To investigate whether the basal plasma amino acid concentrations in patients with traumatic brain injury (TBI) have returned to levels found in healthy controls at about 17 months postinjury and to determine the effect of intake of a mixture of essential amino acids (EAA) on plasma amino acid concentrations in TBI versus healthy controls. Design Peripheral venous amino acid concentrations in subjects with TBI were compared with concentrations in healthy controls both at rest and for 1 hour after intake of 7g of EAA. Setting Postacute brain injury rehabilitation center. Participants Six men with TBI (age ± standard deviation, 27±6y; months postinjury, 17±4) and 6 healthy men (age, 43±7y). Intervention Intake of a drink consisting of 7g of EAA. Main Outcome Measures Individual and total plasma amino acid concentrations. Results Total amino acid concentration was about 12% lower in TBI versus controls ( P=.022). Valine was reduced by 33% in the TBI group versus controls ( P=.003), whereas the other EAA did not differ between groups. After intake of the EAA drink, plasma non-EAA increased to a significantly higher level in controls versus TBI subjects ( P=.017). Conclusions Plasma total amino acid concentration is still reduced 17 months postinjury in patients with TBI versus healthy controls, mainly because of a lower valine level. This may be of importance for both brain and muscle metabolic functions, and warrant further study. Further, ingested EAA are apparently not as readily converted to non-EAA in TBI patients as in healthy controls, suggesting that in recovery from TBI, certain non-EAA may become provisionally essential.

The hyperinsulinemic amino acid clamp increases whole-body protein synthesis in young subjects

We propose that hyperinsulinemia stimulates protein synthesis when postabsorptive plasma amino acid (AA) concentrations are maintained. During a euglycemic hyperinsulinemic clamp, many AA, notably the branched-chain amino acids (BCAA), decline markedly. Therefore, we tested whether individual plasma AA could be maintained within the range of postabsorptive concentrations to assess the effects of insulin, infused at 40 mU/m 2 · min on whole-body protein and glucose metabolism, using [1- 13C]-leucine and [3- 3H]-glucose methodology. Validation studies of background [ 13C] enrichment and breath 13CO 2 recovery factors were performed in a subset of 6 subjects. In 10 healthy, young men, infusion rates of an AA solution were based on fluorometric determinations of total BCAA every 5 minutes. All 21 plasma AA remained in the target range; 15, including the BCAA, alanine, and glycine were within 13% of baseline, and only 6 (Thr, His, Arg, Asn, Cit, Tyr) varied more (18% to 42%). Notably, both leucine flux and nonoxidative leucine R d (protein synthesis) increased with insulin (2.36 ± 0.06 to 2.81 ± 0.10 and 1.79 ± 0.05 to 2.18 ± 0.10 μmol/kg fat-free mass (FFM) · min, respectively; P < .0005) while leucine oxidation only tended to increase ( P = .05) and endogenous leucine R a (protein breakdown) decreased by 18% (2.36 ± 0.06 to 1.94 ± 0.09 μmol/kg FFM · min; P < .0005), resulting in a marked elevation of net protein synthesis (−0.57 ± 0.02 to 0.24 ± 0.02 μmol/kg FFM · min; P < .0000001). Thus, in vivo protein anabolism was induced when maintaining postabsorptive plasma amino acid concentrations during hyperinsulinemia through a suppression of whole-body protein breakdown, no significant change in oxidation and an elevation of synthesis compared with postabsorptive conditions.

A High-Protein Meal Exceeds Anabolic and Catabolic Capacities in Rats Adapted to a Normal Protein Diet

The postprandial fixation of dietary nitrogen in splanchnic and peripheral tissues as well as its dynamic transfer to the nitrogen pools of the body were quantified in rats subjected to an acute augmentation of dietary protein. For this purpose, we traced the dietary protein and studied the immediate fate of exogenous nitrogen in many tissues and biological fluids. Rats were adapted to a diet providing an adequate protein level (14 g/100 g), and then fed a meal containing either 0.42 g (Group A) or 1.50 g (Group H) of [(15)N]-labeled milk protein. The amounts of exogenous nitrogen transferred to urea (0.32 +/- 0.04 vs. 2.46 +/- 0.25 mmol, respectively), incorporated in splanchnic (0.41 +/- 0.02 vs. 0.87 +/- 0.10 mmol) and peripheral (1.65 +/- 0.84 vs. 2.36 +/- 0.49 mmol) tissue protein were higher in group H than in group A. Individual plasma amino acids (AA) [(15)N]-enrichments showed that AA respond differentially to an acute augmentation of dietary intake. This work provides new descriptive and quantitative information on the metabolic fate of dietary nitrogen in the postprandial state. It highlights the higher integration of a surplus of dietary nitrogen in the tissues even if it is rapidly limited by saturation of the protein synthesis capacities. The main metabolic response remains the stimulation of AA degradation, leading to a large rise in urea production. However, both anabolic and catabolic systems are exceeded, resulting in an elevation of peripheral AA and negative feedback on the gastric emptying rate.

Lactation during hibernation in wild black bears: effects on plasma amino acids and nitrogen metabolites.

This study examined the seasonal and reproductive influences on individual plasma amino acid concentrations and nitrogen metabolites in a black bear population (Ontario, Canada). During hibernation, 11 of 23 plasma amino acids were significantly higher (13%-108%) in lactating than in nonlactating females, without an alteration in plasma total protein or total essential or nonessential amino acid levels. The greatest changes were observed in glutamine, arginine, and glycine levels. Plasma urea, urea/creatinine, and ammonia levels were significantly lower in hibernating compared with active female bears, but lactation had no effect on these parameters. Taken together these results show that lactation during hibernation is an additional metabolic challenge that results in increased mobilization of individual plasma amino acids and no accumulation of nitrogen end products, underlining the remarkable efficiency of amino acid and urea recycling in denning female black bears.

Plasma amino acid levels after carbon tetrachloride induced acute liver damage. A dose-response and time-response study in rats.

The aims of the present study were to assess the changes of individual plasma amino acid levels in relation (1) to the severity of liver damage and (2) to the process of liver recovery. Acute liver injury was induced by an intragastric administration of CCl4 diluted in olive oil in doses of 2, 4 and/or 6 g of CCl4 per kg b.w. The control rats received olive oil only. Animals were sacrificed at 16, 24, 48 and 96 hours after treatment. The severity of liver injury was assessed by histological examination, by changes in ALT and AST in the blood plasma and by changes in liver weight. Statistical analysis was carried by ANOVA, p < 0.05 was considered significant. The Spearman rank correlation coefficient was used as a measure of the degree of linear relationship between variable and dose. In the period of the development of acute liver damage, i.e. at 16 and 24 hours after treatment, an increase in blood plasma amino acid levels and positive correlations with the dose of CCl4 were observed for most individual amino acids. The only exception was arginine which decreased in a dose dependent manner. At a phase of liver recovery, i.e. at 48 and 96 hours after CCl4 treatment, the concentrations of some individual amino acids decreased below the control values. The negative correlation with the dose of CCl4 occurred for taurine and isoleucine (at 48 hours) and taurine, threonine, valine, methionine, isoleucine and leucine (at 96 hours).

Quantification of incorporation of [15N]ammonia into plasma amino acids and urea.

The incorporation of 15N into individual plasma amino acids and urea was quantified in five human subjects who received 15NH4Cl either orally or intravenously for 6 h. After oral tracer administration, the highest enrichment was achieved by arginine, followed by urea and glutamine; distribution of 15N within glutamine was 55% amide and 45% amino N. Glutamine achieved the highest enrichment after the intravenous administration of tracer, with a distribution of 92% amide and 8% amino N. The relative distribution pattern of 15N incorporation was quantified from the rate at which 15N initially appeared in each plasma component. Amino acids (especially arginine, glutamine, and glutamate) accounted for greater than one-half (54%) of the orally administered tracer that was initially recovered in plasma components, compared with 46% initial appearance for urea; for the intravenous tracer, amino acids accounted for 78% of initial appearance of tracer compared with 22% for urea. Our results highlight the involvement of the splanchnic bed in the utilization of orally administered ammonia (preferential incorporation of oral tracer into arginine, urea, glutamate, and the amino N of glutamine) in contrast to the preferential incorporation of systemically administered ammonia into the amide N of glutamine and alanine.

Is the plasma amino acid consumption test an accurate test of exocrine pancreatic insufficiency?

Background/Aims: The amino acid consumption test has been proposed as an accurate test of exocrine pancreatic function. The diagnostic accuracy of this test was determined by simultaneously measuring plasma amino acids and enzyme secretion during stimulation of the pancreas with cholecystokinin octapeptide (CCK-OP) in 60 consecutive patients suspected of having pancreatic insufficiency. Methods: All patients underwent duodenal intubation and intravenous infusion of CCK-OP (40 ng·kg −1 ·h−1). Pancreatic enzyme (lipase and trypsin) outputs and plasma amino acids were measured for a period of 1 hour. Total and individual plasma amino acids were quantitated by ion-exchange chromatography. The severity of pancreatic insufficiency was graded on the basis of enzyme output during CCK-OP infusion. Results: There was no relationship between pancreatic enzyme output and plasma concentrations of individual or total amino acids before or during CCK-OP stimulation. Using a total amino acid decrease of 12% as the cutoff, the amino acid consumption test was 91% sensitive, but very nonspecific (21% specificity) for detection of pancreatic insufficiency. Conclusions: The amino acid consumption test with CCK-OP stimulation does not discriminate between patients with normal and impaired exocrine pancreatic secretion.

Plasma Amino Acid Response to Ingestion of L-Amino Acids and Whole Protein

The effect of whole protein and L-amino acid ingestion on plasma amino acid concentrations was investigated in 10 men. Each subject ingested equivalent amounts of amino acids as cottage cheese (session 1), an L-amino acid mixture (session 2), and cottage cheese and L-amino acids (session 3). Postprandial changes from baseline were larger for essential versus nonessential amino acids in each session. Higher and more rapid rises followed by more rapid declines in individual plasma amino acid concentrations were observed after ingestion of L-amino acids alone or with whole protein than after ingestion of an equivalent amount of amino acids as whole protein. Individuals receiving the majority of their essential amino acid and nitrogen needs from elemental products may need, for example, to consume them more frequently or after consumption of other foods in an effort to slow down absorption rates.

Plasma Amino Acid Response to Ingestion of L‐Amino Acids and Whole Protein

SummaryThe effect of whole protein and L‐amino acid ingestion on plasma amino acid concentrations was investigated in 10 men. Each subject ingested equivalent amounts of amino acids as cottage cheese (session 1), an L‐amino acid mixture (session 2), and cottage cheese and L‐amino acids (session 3). Postprandial changes from baseline were larger for essential versus nonessential amino acids in each session. Higher and more rapid rises followed by more rapid declines in individual plasma amino acid concentrations were observed after ingestion of L‐amino acids alone or with whole protein than after ingestion of an equivalent amount of amino acids as whole protein. Individuals receiving the majority of their essential amino acid and nitrogen needs from elemental products may need, for example, to consume them more frequently or after consumption of other foods in an effort to slow down absorption rates.

Growth and Metabolic Responses in Low-Birth-Weight Infants Fed Human Milk Fortified with Human Milk Protein or with a Bovine Milk Protein Preparation

Unfortified human milk does not normally provide enough protein to secure maximal growth in low-body-weight (LBW) infants. Due to the practical difficulties in obtaining human milk protein (HMP), a bovine milk protein preparation (BMP) was designed by computer calculation to contain as close as possible the amino acid composition of the nutritionally available human milk proteins. Twenty-one AGA, LBW infants (BW of 1,180 to 1,600 g, GA of 27 to 33 weeks) were randomly assigned to be fed HM enriched either with HMP (9 infants) or BMP (12 infants). When full volume intake (170 ml/kg/day) was reached, the protein intakes were 3.6 +/- 0.5 and 3.3 +/- 0.3 g/kg/day, respectively, in the two diet groups. During the study period of 24 days, the infants achieved intrauterine or better weight gains: 32.9 +/- 3.3 g/day (17.7 +/- 1.9 g/kg/day) in the HMP group and 34.7 +/- 7.3 g/day (18.3 +/- 3.5 g/kg/day) in the BMP group. Serum urea nitrogen, acid-base status, and albumin values were normal and similar in both groups of infants. Plasma concentrations of total essential and total amino acids at the end of the study were 3,999 and 1,539 mumol/L and 3,899 and 1,422 mumol/L in the HMP and the BMP groups, respectively. The concentrations of all individual plasma amino acids were similar in both feeding groups. These results show that feeding human milk fortified with a modified bovine milk protein preparation produces satisfactory growth and a plasma amino acid profile similar to that found in LBW infants fed exclusively human milk protein at similar intakes.

Growth and Metabolic Responses in Low‐Birth‐Weight Infants Fed Human Milk Fortified with Human Milk Protein or with a Bovine Milk Protein Preparation

Unfortified human milk does not normally provide enough protein to secure maximal growth in low‐body‐weight (LBW) infants. Due to the practical difficulties in obtaining human milk protein (HMP), a bovine milk protein preparation (BMP) was designed by computer calculation to contain as close as possible the amino acid composition of the nutritionally available human milk proteins. Twenty‐one AGA, LBW infants (BW of 1,180 to 1,600 g, GA of 27 to 33 weeks) were randomly assigned to be fed HM enriched either with HMP (9 infants) or BMP (12 infants). When full volume intake (170 ml/kg/day) was reached, the protein intakes were 3.6 ± 0.5 and 3.3 ± 0.3 g/kg/day, respectively, in the two diet groups. During the study period of 24 days, the infants achieved intrauterine or better weight gains: 32.9 ± 3.3 g/day (17.7 ± 1.9 g/kg/day) in the HMP group and 34.7 ± 7.3 g/day (18.3 ± 3.5 g/kg/day) in the BMP group. Serum urea nitrogen, acid‐base status, and albumin values were normal and similar in both groups of infants. Plasma concentrations of total essential and total amino acids at the end of the study were 3,999 and 1,539 μmol/L and 3,899 and 1,422 μmol/L in the HMP and the BMP groups, respectively. The concentrations of all individual plasma amino acids were similar in both feeding groups. These results show that feeding human milk fortified with a modified bovine milk protein preparation produces satisfactory growth and a plasma amino acid profile similar to that found in LBW infants fed exclusively human milk protein at similar intakes.

Ribosome and free amino acid content in muscle during hemodialysis

Patients (N = 8) with chronic renal failure and uremia treated with hospital hemodialysis were in a pilot study investigated before and after a single hemodialysis session. The extracorporeal dialysis circuit was flushed regularly with saline to avoid clotting and the use of heparin. Percutaneous skeletal muscle biopsies were taken before and after the dialysis to determine the content of free amino acids together with the concentration and size distribution of ribosomes before and after dialysis. After dialysis the alanine concentration in muscle decreased by 20% (P less than 0.05), while all other amino acids were unaffected. The total ribosome concentration per mg of DNA decreased by 31% (P less than 0.01) and the relative proportion of polyribosomes by 7% (P less than 0.05) after the dialysis compared to predialytic values. All individual plasma amino acids decreased during the dialysis procedure except for threonine and arginine, which were unaltered, and leucine and isoleucine, which increased. The decline in ribosome and polyribosome content together with the changes in amino acid levels indicate a low capacity for protein synthesis and increased catabolism in muscle of hemodialyzed patients.

Synthesis of Urea after a Protein-rich Meal in Normal Man in Relation to Ageing

An age-related decline in the functional capacity of the liver has been repeatedly demonstrated by means of dynamic tests. We measured the urea-N synthesis rate in response to a protein-rich meal in 24 healthy subjects divided into three age-groups (less than or equal to 55 years, 56-70 years; greater than or equal to 71 years). No differences were observed in the basal state. The peak urea synthesis and the mean urea synthesis in the 5 hours after the meal were blunted with increasing age, and a negative correlation was present between mean or peak urea synthesis and age (r = -0.572 and r = -0.541, respectively). No differences in basal and post-meal total alpha-amino-nitrogen or individual plasma amino acids were observed. Hormone responses were similar. Galactose elimination capacity was also reduced with increasing age, and correlated with mean and peak urea synthesis after a protein mean (r = 0.640 and r = 0.591, respectively). These data suggest that the capacity of the liver to produce urea in response to a protein-rich meal is reduced in the elderly in relation to a decreased functional liver cell mass.

25. SUPPLEMENTATION OF FRESH HUMAN MILK WITH HUMAN MILK PROTEIN FOR FEEDING VERY-LOW-BIRTH-WEIGHT (VLBW) INFANTS

18 VLBW-infants (BW = 800-1600 g, AGA) were studied until discharge at a weight of 2000 g. All infants received mother's own milk. 9 received such milk supplemented with 1 g of ultrafiltrated human milk protein. At a milk intake of 180 ml/kg/d the protein intake varied between 2 and 4.5 g/kg/d. Protein fortification of human milk produced a higher weight gain (32.2 g/d vs. 26.4 g/d, p<0.005). The best protein utilization (weight gain per g of protein) was obtained at a protein intake of about 3 g/kg/d. Blood urea nitrogen (BUN) concentrations and other indices of protein metabolism correlated to protein intake. The mean BUN concentration was 7.2 mg% in the protein supplemented group. Protein supplementation resulted in an elevation of plasma total amino acid concentrations at the end of the study (2788 vs. 2316 μmoles/l). Individual plasma amino acid concentrations also varied with protein intake. A daily human milk protein intake of about 3 g/kg produced a rate of weight gain corresponding to that found in utero at the corresponding gestational age in VLBW-infants. The plasma responses of protein metabolism observed at this protein intake are similar to those found in term infants, breast-fed. We suggest that these results can be used as a model when evaluating feeding regimens with non-human proteins in VLBW-infants.