Plasma Amino Acid Values Research Articles

Utilizing augmented artificial intelligence for aminoacidopathies using collaborative laboratory integrated reporting- A cross-sectional study

IntroductionPlasma amino acids profiling can aid in the screening and diagnosis of aminoacidopathies. The goal of the current study was to analyze and report the metabolic profiles of plasma amino acid (PAA) and additionally to compare PAA-reference intervals (RI) from Pakistan with more countries utilizing Clinical Laboratory Integrated Reports (CLIR).MethodsThis was a cross sectional prospective single center study. Twenty-two amino acids were analyzed in each sample received for one year at the clinical laboratory. Data was divided into reference and case data files after interpretation by a team of pathologists and technologists. All PAA samples were analyzed using ion-exchange high-performance chromatography. The CLIR application of Amino Acid in Plasma (AAQP) was used for statistical analysis for both data sets and post-analytical interpretive tools using a single condition tool was applied.ResultThe majority of 92% (n = 1913) of PAA profiles out of the total 2081 tests run were non-diagnostic; the PAA values were within the age-specific RI. The PAA median was in close comparison close to the 50th percentile of reference data available in CLIR software. Out of the total 2081 tests run, one hundred and sixty-eight had abnormal PAA levels; 27.38% were labeled as non-fasting samples, and the main aminoacidopathies identified were Phenylketonuria and Maple Syrup Urine Disorder.ConclusionAn agreement of >95% was observed between the reporting done by the pathologists and technologists’ team and then after the application of CLIR. Augmented artificial intelligence using CLIR can improve the accuracy of reporting rare aminoacidopathies in a developing country like ours.

Plasma amino acid pools in the umbilical cord artery show lower 15N natural isotope abundance relative to the maternal venous pools

ABSTRACT 15N natural isotope abundance (NIA) is systematically higher in infants’ hair than in that of their mothers at birth. This study aimed to investigate this difference in plasma pools. We compared 15N NIA values for plasma amino acid (AA) pools (free + protein-bound) in the umbilical cord artery (UCA) and vein (UCV) and in the maternal vein (MV) at birth. This preliminary study included 7 mother–infant dyads. Whole plasma was treated (HCl) to hydrolyze protein. Following derivatization, AAs were separated using gas chromatography and compound-specific 15N NIA values were measured on-line using an isotope ratio monitoring mass spectrometer. 15N NIA plasma AA pools in the UCA and UCV were highly correlated to the MV, r 2 > 0.89 and r 2 > 0.88 (both P < 10−4) respectively. The full model found a significant effect of sampling compartment (P = 0.02) and AA type (P < 0.0001) on 15N NIA plasma AA values. 15N NIA plasma AA was 0.74 ‰ higher (P = 0.01) in the MV than in the UCA. This study indicates that a decrease in 15N NIA for plasma AA pools occurs in the fetal–placental unit. Trial registration: ClinicalTrials.gov identifier: NCT00607061.

Characterization of aminoaciduria and hypoaminoacidemia in dogs with hepatocutaneous syndrome.

OBJECTIVE To characterize aminoaciduria and plasma amino acid concentrations in dogs with hepatocutaneous syndrome (HCS). ANIMALS 20 client-owned dogs of various breeds and ages. PROCEDURES HCS was definitively diagnosed on the basis of liver biopsy specimens (n = 12), gross and histologic appearance of skin lesions (4), and examination of skin and liver biopsy specimens (2) and presumptively diagnosed on the basis of cutaneous lesions with compatible clinicopathologic and hepatic ultrasonographic (honeycomb or Swiss cheese pattern) findings (2). Amino acid concentrations in heparinized plasma and urine (samples obtained within 8 hours of each other) were measured by use of ion exchange chromatography. Urine creatinine concentration was used to normalize urine amino acid concentrations. Plasma amino acid values were compared relative to mean reference values; urine-corrected amino acid values were compared relative to maximal reference values. RESULTS All dogs had generalized hypoaminoacidemia, with numerous amino acid concentrations < 50% of mean reference values. The most consistent and severe abnormalities involved glutamine, proline, cysteine, and hydroxyproline, and all dogs had marked lysinuria. Urine amino acids exceeding maximum reference values (value > 1.0) included lysine, 1-methylhistidine, and proline. CONCLUSIONS AND CLINICAL RELEVANCE Hypoaminoacidemia in dogs with HCS prominently involved amino acids associated with the urea cycle and synthesis of glutathione and collagen. Marked lysinuria and prolinuria implicated dysfunction of specific amino acid transporters and wasting of amino acids essential for collagen synthesis. These findings may provide a means for tailoring nutritional support and for facilitating HCS diagnosis.

Index of Suspicion

Index of Suspicion

Plasma amino acids in pregnancy, placental intervillous space and preterm newborn infants

Plasma amino acid levels have never been studied in the placental intervillous space of preterm gestations. Our objective was to determine the possible relationship between plasma amino acids of maternal venous blood (M), of the placental intervillous space (PIVS) and of the umbilical vein (UV) of preterm newborn infants. Plasma amino acid levels were analyzed by ion-exchange chromatography in M from 14 parturients and in the PIVS and UV of their preterm newborn infants. Mean gestational age was 34 +/- 2 weeks, weight = 1827 +/- 510 g, and all newborns were considered adequate for gestational age. The mean Apgar score was 8 and 9 at the first and fifth minutes. Plasma amino acid values were significantly lower in M than in PIVS (166%), except for aminobutyric acid. On average, plasma amino acid levels were significantly higher in UV than in M (107%) and were closer to PIVS than to M values, except for cystine and aminobutyric acid (P < 0.05). Comparison of the mean plasma amino acid concentrations in the UV of preterm to those of term newborn infants previously studied by our group showed no significant difference, except for proline (P < 0.05), preterm > term. These data suggest that the mechanisms of active amino acid transport are centralized in the syncytiotrophoblast, with their passage to the fetus being an active bidirectional process with asymmetric efflux. PIVS could be a reserve amino acid space for the protection of the fetal compartment from inadequate maternal amino acid variations.

Changes in plasma and urinary taurine and amino acids in runners immediately and 24h after a marathon.

Changes in urinary and plasma taurine and amino acids have been evaluated in trained runners competing in the Rotterdam Marathon, 1998, both immediately after completing the event and 24h after recovery. There were significant changes in the urinary amino acids excretion, the majority showing a significant decrease both immediately at the completion of the Marathon and after 24h recovery. In contrast urinary taurine excretion increased immediately post Marathon, although not significantly as the range of results was wide. Such changes in urinary taurine correlated with percentage changes in plasma creatine kinase both immediately post race, (r = 0.972, P < 0.001), and 24h later (r = 0.872, P < 0.001), possibly indicating that the source of the taurine was muscle. Significant correlations between the individual values for urinary and plasma amino acids in all of the athletes were calculated for taurine (r = 0.528), glycine (r = 0.853), threonine (r = 0.749), alanine (r = 0.747), serine (r = 0.620), glutamine (0.614), arginine (r = 0.507), histidine (r = 0.470) and valine (r = 0.486). Changes in the mean plasma concentrations of amino acids were comparable to our previously published data (Ward et al., 1999) the majority showing significant decreases immediately and 24h post Marathon, such an adaptation being due primarily to their utilisation for gluconeogenesis. However, in contrast, the mean taurine concentrations were significantly elevated both post race, P < 0.01 and after 24h, P < 0.05. The physiological response by the muscle to exhaustive exercise, particularly with regard to changes in plasma and urinary taurine concentrations remain to be elucidated, but is probably related to muscle function impairment. The increase in taurine urinary excretion could be used as an indicator of muscle damage occurring during exhaustive exercise. Whether taurine supplementation would minimise such changes is an interesting scientific question and merits investigation.

Desequilibrio de aminoácidos plasmáticos en pacientes autistas y en sujetos con trastorno de déficit de atención con hiperactividad

Plasma and brain amino acids are influenced by dietary intake. Alterations of plasma amino acid concentrations have been reported in neuropsychiatric disorders. To analyse the plasma amino acid values in subject diagnosed with autism, with attention deficit/hyperactivity disorder (ADHD), and healthy subjects as controls. Forty subjects affected by autism, 11 with ADHD and 41 healthy subjects (age range 3 18 years old) were included in this study. Peripheral venous blood was obtained in fasting condition, collected in EDTA tubes and centrifuged. Plasma was de proteinised with sulfosalicylic acid. Amino acids were analysed by ion exchange liquid chromatography with an LKB amino acid analyser with sodium citrate elution system and ninhydrin reaction. Results were expressed as mmol/L. In both disorders a diminution of phenylalanine and glutamine plasma concentrations was observed beside an increase of glycine. Lysine appeared increased only in autistic subjects. These alterations produce an imbalance with the rest of plasma amino acids competing at the brain blood barrier by the same transport system thus causing alterations in the metabolism and/or transport of amino acids to the brain, altering CNS functions. The phenylalanine decreasing, beside glycine increasing appear to support the hypothesis of a disorder in the inhibitory neurotransmission system, especially in ADHD. The diminution of phenylalanine and the increasing of lysine in autism are suggestive that these two amino acids are metabolically related.

Effect of protein/energy ratio on growth and behavior of premature infants: Preliminary findings

Premature infants weighing less than 1550 gm at birth were randomly assigned to receive one of three formulas identical in composition except for protein content (2.2, 2.7, and 3.2 gm.100 kcal-1) to determine the effects on growth, protein nutritional status, and behavior. Data collected for 2 weeks from the time of achieving an enteral energy intake of 100 kcal.kg-1.day-1 included measurements of weight, length, head circumference, and skin-fold thickness, and concentrations of plasma amino acids, serum total protein, prealbumin, retinol-binding protein, and urea nitrogen. In a subset of infants, behavior was assessed at the end of the feeding study with the Neonatal Behavior Assessment Scale. Except for the concentrations of plasma amino acids, there were no significant differences in growth or in other biochemical measurements among the three groups, but there were significant differences in the orientation, habituation, and stability clusters of the behavior assessment. Further, there were significant correlations between the plasma amino acid values and the behavioral clusters. These preliminary data suggest a relationship between protein intake in the neonatal period and behavioral outcome at the end of the feeding period in the absence of differences in growth and gross markers of protein nutritional status. The behavioral items noted to differ among the groups may indicate later cognitive outcome; detailed studies about behavioral responses to neonatal dietary intakes and later outcome seem indicated.

Diet-related reference values for plasma amino acids in newborns measured by reversed-phase HPLC

We have measured by reversed-phase HPLC concentrations of amino acids in plasma in groups of 80 normal appropriate-weight term babies fed from birth either a casein formula (WhiteCap SMA, n = 26), a whey formula (Gold Cap SMA, n = 26), or breast milk (n = 28). They were studied from day 11 to week 15 postpartum. The trend was towards an increase in amino acid concentrations in plasma with age, more marked in formula-fed than in breast-fed infants. Reference values were derived for each group. Both formula-fed groups showed several differences from the breast-fed group. Detailed examination indicated that tyrosine, phenylalanine, and methionine concentrations were increased in the casein-fed group greater than 20% of the time, but only threonine was similarly increased in the whey-fed group. Other amino acids, different ones for each formula group, were increased less frequently. There were no consistent correlations with any aspect of infant growth. Appropriate reference values are important for interpreting amino acid concentrations in plasma from newborns and for evaluating the effects of any future dietary modifications to infant formulas. HPLC analysis provides a suitable highly sensitive method for undertaking such studies.

Nitrogen sparing effect of ornicetil ® in the immediate post-operative state—Plasma and muscle amino-acids

In an earlier report we demonstrated that parenteral nutrition (TPN) with addition of 1(+)ornithine alpha-ketoglutarate (Ornicetil ®) markedly improved nitrogen economy in the immediate post-operative period compared to controls given isocaloric and isonitrogenous TPN but without Ornicetil ®. In the present study, plasma and intracellular muscle free amino-acid concentrations were measured in 13 patients before and 3 days after major elective abdominal surgery; seven patients without and six with Ornicetil ® supplementation. The pre-operative values for plasma and muscle free amino-acids did not differ from those derived from age matched health subjects. The direction of post-operative alterations in plasma amino-acid concentrations were similar in both groups, consistent with the earlier reported post-operative pattern, although the elevations of BCAA, proline and ornithine were much more accentuated in the Ornicetil ® group. After surgery the majority of the commonly observed intracellular changes were abolished or minimised in patients receiving Ornicetil ®, while the intracellular depletion of glutamine persisted and the levels of ornithine and proline were markedly elevated as a consequence of Ornicetil ® supply. A tentative explanation for the biochemical action of Ornicetil ® is given.

Indices of protein metabolism in term infants fed either human milk or formulas with reduced protein concentration and various whey/casein ratios

Hyperaminoacidemia is evident in infants fed either whey-dominant or casein-dominant formula containing 2.2 g protein/100 kcal. We assessed protein metabolism in infants fed formulas with reduced protein contents and various whey/casein ratios. Term infants (n = 40) received either human milk or formula containing 1.8 g protein/100 kcal and whey/casein ratios 18:82, 34:66, or 50:50. At ages 4 and 8 weeks, growth indices and mean serum concentrations of retinol binding protein, albumin, total protein, and serum urea nitrogen were similar, as were mean plasma concentrations of total amino acids, total essential amino acids, and their ratio. Compared with infants fed human milk, those fed formula had plasma concentrations similar for valine, lysine, arginine, tyrosine, histidine, threonine, and free and total cyst(e)ine; elevated for phenylalanine, methionine, and citrulline; and depressed for taurine and tryptophan. Except for leucine, mean plasma amino acid values varied similarly among formula groups despite differences in intakes. Our data indicate that feeding formulas providing 1.8 g protein/100 kcal results in many indices of protein metabolism characteristic of human milk feeding. However, certain differences are noted, suggesting the need for further manipulation of specific amino acid patterns of infant formulas.

Plasma free amino acid values in normal children and adolescents

We measured plasma free amino acids in 52 children (mean age 8 years) and 80 adolescents (mean age 16 years); conditions of diet and time of day were similar in the two groups. The protocols allowed us to compare their interindividual variation with values previously reported by us for adults. In children, the values for all but seven amino acids were normally distributed; in adolescents there were only six exceptions. Effects of age were apparent: values for only two amino acids were higher in children than adolescents. Values were significantly lower for ten amino acids in children v adolescents and for 11 amino acids in younger children (1 to 6 years) v older children (7 to 12 years). An effect of sex was apparent for five amino acids in adolescents; such differences were not apparent in children. All differences were quasicontinuous and occurred within the global distributions that define values for plasma amino acids in normal children and adolescents. Two artifacts (choice of anticoagulant and delay in deproteinization) affected values for taurine and cystine, respectively.

Determination of plasma amino acids by gas chromatography

A complete methodology, incorporating a novel clean-up technique, for quantitative determination of amino acids in plasma by gas chromatography is described. Glucose, a component causing major analytical interference, is removed by an enzymic reaction included in the pre-chromatographic clean-up. The procedure for derivatisation of amino acid standards is shown to be reproducible down to a level of 2.5 μg for each amino acid, relative standard deviations for all amino acids except arginine and histidine being 3% or lower. For the entire procedure applied to plasma, relative standard deviations for most amino acids are below 5% with recoveries ranging from 90 to 120%. Normal values, obtained using eighteen plasma samples, are in reasonable agreement with published data. Plasma amino acid values were determined simultaneously by gas chromatographic and ion-exchange chromatographic techniques. Statistical evaluation shows there to be no significant difference between corresponding values for eleven amino acids. Values for tyrosine, histidine and particularly phenylalanine show significant differences ( p < 0.001).

Normal plasma free amino acid values in adults: The influence of some common physiological variables

We measured plasma free amino acids in ten healthy adults (five males, five females, ages 26 to 54 years), at four times of day, under two dietary protocols. The design allowed us to measure the effects of some common physiological variables on the metrical distributions (mean, SD, skewness, kurtosis) of 80 values (in most cases), for each of 20 amino acids. Analysis of variance indicates that individuals in a “public” population possess “private” phenotypes for 18 plasma amino acids under typical external experiences; the exceptions were aspartate and taurine. The collective infradiem variation rarely exceeded 50% of the nadir value for any amino acid. We conclude that genotype is an important determinant of plasma amino acid phenotype in normal persons, and that there is striking homeostasis of plasma amino acid values in human adults adapted to normal daily activity.

Growth velocity and plasma amino acids in the newborn.

Plasma amino acid levels in newborn babies are often measured as part of a screening for inherited metabolic disease, or less commonly as part of a nutritional assessment. We have examined certain factors which affect the levels as measured in low birth weight babies during the first 3 wk of life. As in other studies, plasma amino acid concentrations were shown to fall with increasing gestational and postnatal age, and to reflect to some extent the amino acid composition of the dietary protein. In addition, however, plasma branched-chain amino acids and cystine were found to be inversely related to growth velocity and nitrogen retention. These results could be interpreted to suggest that some low birth weight babies were malnourished. However accompanying anthropometric and clinical data showed that these particular babies were healthy and growing rapidly; they were unlikely to be truly malnourished. Rather we suggest they were experiencing "protein economy" resulting from their high growth rate, and would, therefore, have benefited from increased dietary protein. It seems that growth velocity, as well as maturity and diet, must be considered when interpreting plasma amino acid values in an individual baby. There are two implications for the nutrition of the low birth weight baby. The higher plasma threonine concentrations found in the babies receiving the demineralized whey formula does prompt a word of caution when further increase in the whey:casein ratio is contemplated. At energy intakes around 130 kcal/kg/day, protein may become a limiting nutrient both in terms of quality and quantity.

Plasma and cerebrospinal fluid amino acid concentrations in phenylketonuria during the newborn period

Plasma and cerebrospinal fluid amino acid values were determined in 29 infants 9 to 30 days of age with a confirmed diagnosis of phenylketonuria. Phenylalanine concentrations in plasma and cerebrospinal fluid were markedly elevated; the degree of elevation in the cerebrospinal fluid had a significant relationship to that of the plasma. The only other significant deviations in the plasma were reductions in the threonine and tyrosine values. Cerebrospinal fluid threonine, alanine, and arginine concentrations were reduced, whereas those of serine, isoleucine, and histidine were elevated. This combined deficiency and excess of amino acids in the central nervous system may have a significant effect on protein synthesis at a time in life when this synthesis and turnover is most active.

Plasma Amino Acid Profiles and Amino Acid Losses in Patients Undergoing CAPD

Fasting plasma amino acid levels and 24hour amino acid losses in the dialysate were measured in six nondiabetic female and six diabetic male patients on CAPD. Comparison of their plasma amino acid values with sex matched controls showed that CAPD did not restore the plasma amino acid levels of these patients to normal, and that the abnormalities in the non-diabetics were more marked than in the diabetics. The daily total amino acid losses in the dialysate were small relative to protein intake, averaged 2.25 9 per day and were similar for the non-diabetic and diabetics. The concentrations of most amino acids in the dialysate were proportional to their plasma concentrations. Loss of amino acids in the dialysate does not account for the abnormal plasma patterns of CAPD patients.

A controlled trial of glucose versus glucose and amino acids in premature infants

A controlled study comparing two intravenous fluid regimens was performed in sick, premature infants. The regimens were isocaloric at 60 calories/kg/day, one providing glucose alone, the other glucose plus 2.5 gm/kg of amino acids. There was no difference in changes in body weight between the two groups; infants receiving glucose alone were in negative nitrogen balance; those receiving glucose plus amino acids were in positive nitrogen balance. Plasma amino acid values were compared to published, postprandial normal values. The TEAA and TAA of infants receiving amino acids were not different from normal. Values of TEAA and TAA of infants receiving glucose alone were significantly lower. Essential fatty acid deficiency developed in infants receiving amino acids but not in those receiving glucose alone. It is concluded that the glucose plus amino acid regimen results in anabolism without undue metabolic costs.

Minimum Nitrogen Requirement from Glandless Cottonseed Protein for Nitrogen Balance in College Women

Seven women, 18 to 23 years of age, were fed cooked cottonseed products for 42 days in order to determine the minimum nitrogen requirements for glandless cottonseen flour after baking. The women consumed from 81 to 213 mg N/kg body weight from cottonseed protein. Nitrogen intake from each experimental period was calculated from the average nitrogen content of the cottonseed products consumed each day of the experiment period. Nitrogen excretion was determined from the measurement of nitrogen in a total collection of urine and feces for each experimental period plus an obligatory loss of 5 mg/kg body weight. Fasting blood samples were taken prior to the study and at the end of each 7-day experimental period thereafter. The minimum requirement for cottonseed protein to maintain a positive nitrogen balance was 106 mg N/kg body weight. For the "reference woman," weighing 58 kg, at least 6.1 g of cottonseed flour nitrogen would be required to maintain nitrogen equilibrium. Plasma amino acid values of threonine, proline, valine, isoleucine, leucine, tyrosine, and lysine decreased significantly from day 0 to day 7 of the study. There were no significant differences in these plasma amino acids thereafter. Cottonseed flour incorporated into baked products maintained nitrogen balance in college women with no change in their nutritional status.

Amino acid requirements of the breeding sow. 2. The dietary lysine requirement of the lactating sow.

1. Two experiments, involving six lactating Landacre x (Landrace x Large White) sows were undertaken to study the lysine requirement of the lactating sow and to identify the second limiting amino acid by means of interpretation of plasma amino acid and blood urea levels. 2. A basal diet composed mainly of equal amounts of ground barley and ground wheat supplemented with mineral and vitamin mixtures was used. This diet was supplemented with synthetic amino acids (lysine threonine, tryptophan, methionine and isoleucine). 3. Plasma amino acid and blood urea values showed a close agreement and indicated that lysine intake above 38.4 g/d was in excess of the requirement level. 4. Plasma amino acid values suggested tryptophan to be the second limiting amino acid whereas blood urea values suggested threonine to be the second limiting amino acids.