Biomedical subjects

V R Young

Publications and source records attributed to V R Young.

At least 91 records · Page 5Linked to original sources

PubMed1995

Whole body arginine metabolism and nitric oxide synthesis in newborns with persistent pulmonary hypertension.

Despite the potential relevance of the L-arginine-nitric oxide (NO) pathway in the pathophysiology of pulmonary hypertension, no in vivo studies of the kinetics of arginine and NO have been conducted previously in this population. The terminal guanidino N-atom of L-arginine is the precursor for NO, which is oxidized to the stable inorganic nitrogen oxides, nitrite (NO2-) and nitrate (NO3-). Thus, synthesized NO is detected in serum or urine as NO2- and NO3-. The purpose of this investigation was to compare studies of whole body arginine metabolism twice in nine patients with persistent pulmonary hypertension of the newborn (PPHN), using a primed constant i.v. infusion of L-[guanidino-15N2,5,5(2)H2]arginine and L-[5,5,5(2)H3]leucine, first during acute pulmonary vasoconstriction and again during convalescence, and thereby to characterize quantitative aspects of whole body arginine kinetics and NO production, as estimated from the rate of transfer of the 15N-guanidino-label of arginine to urinary nitrate (15NO3-). Arginine flux rates were 84.1 +/- 8.6 mumol.kg-1 h-1 (mean +/- SEM) during acute pulmonary hypertension and increased to 125 +/- 13.2 (p < 0.05) during convalescence, whereas leucine fluxes were unchanged (168.5 +/- 15 versus 178.8 +/- 10.2 mumol.kg-1 h-1), and comparable to those reported in healthy newborns. During convalescence total urinary nitrate excreted increased by 66% (p < 0.05), urinary 15NO3- increased from 0.29 +/- 0.07 to 0.74 +/- 0.15 mumol.d-1 (p < 0.05), and the rate of plasma arginine conversion to NO increased from 10.3 +/- 2.2 to 45.6 +/- 13 mumol.d-1 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine↗

PubMed1994

The plasma flux and oxidation rate of ornithine adaptively decline with restricted arginine intake.

We hypothesized recently that arginine homeostasis is achieved in humans largely by modulating the rate of arginine degradation. We have tested this hypothesis further by measuring in vivo the whole body rate of conversion of arginine to ornithine and ornithine oxidation in six healthy young adults. Subjects received for 6 days an L-amino acid-based diet supplying an arginine-rich or arginine-free intake and on day 7, following an overnight fast, an 8-h tracer protocol (first 3 h, fast state; next 5 h, fed state) was conducted; L-[guanidino-15N2; 5,5-2H]arginine and L-[5-13C]ornithine were given as primed, constant intravenous tracers; measurements of the abundances of various isotopologs of arginine, ornithine, and citrulline in plasma were made, and from these the various kinetic parameters of the metabolism of these amino acids were derived. Arginine and ornithine fluxes were significantly (P < 0.001) reduced in the fed state with arginine-free feeding. The rates of conversion (mumol.kg-1.h-1; mean +/- SD) of plasma arginine to ornithine for arginine-rich were 12.9 +/- 2.6 and 24.7 +/- 4.8 for fast and fed states. These values were 11.1 +/- 3.5 and 9.6 +/- 1.2 (P > 0.05 and P < 0.001), respectively, with an arginine-free diet. [13C]Ornithine oxidation was reduced (P < 0.001) by 46% during the fed state when the arginine-free diet was given. The findings strengthen our hypothesis that homeostasis of arginine metabolism in the human host depends importantly upon a regulation in the rate of arginine degradation with, perhaps, little involvement in the de novo net rate of arginine synthesis.

Adult↗

PubMed1994

Plasma arginine kinetics in adult man: response to an arginine-free diet.

To explore the response of whole-body arginine metabolism to a change in arginine intake, plasma arginine kinetics were investigated in eight healthy adult men who received an L-amino acid diet supplying an Arg-rich or Arg-free intake for 6 days before undergoing a tracer study on day 7. The tracer protocol lasted for 8 hours. For the first 3 hours subjects remained in the postabsorptive (fasted) state, and during the following 5 hours they consumed small meals at 30-minute intervals. Primed continuous intravenous infusions of L-[guanidino-13C]arginine, L-[5,5,5-2H3]leucine, and [15N2]urea were administered to estimate plasma amino acid fluxes and the rate of urea production. For the fasted and fed states, plasma arginine fluxes (mumol.kg-1.h-1, mean +/- SD) were 69 +/- 8 and 87 +/- 12 (P < .01), respectively, for the Arg-rich diet and 63 +/- 14 and 51 +/- 7 (P < .01, from Arg-rich) for the Arg-free diet. Compared with the Arg-rich results, fed-state plasma arginine and ornithine concentrations were decreased (P < .01) and citrulline concentration was increased (P < .01) during the Arg-free diet period. Leucine fluxes and rates of urea production did not differ between the diet groups. The lower fed-state arginine flux in subjects receiving the Arg-free compared with the Arg-rich diet appears to be entirely due to the decreased rate of entry of arginine from the intestine in the former group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Adaptive responses to very low protein diets: the first comparison of ketoacids to essential amino acids.

Eight patients with chronic renal failure (GFR 18.8 +/- 2.7 ml/min) were randomized to a crossover comparison of a very low protein diet (VLPD) containing 0.28 g protein and 35 kcal per kg per day, plus an isosmolar mixture of either ketoacids (KA) or essential amino acids (EAA). Subjects initiated the diets 14 days before hospital admission and following a four-day equilibration, a five-day nitrogen balance (BN) was performed. Whole-body protein turnover (WBPT) was measured during fasting and feeding using intravenous [1-13C]leucine and intragastric [5,5,5-2H3]leucine. Even though the VLPD/KA regimen contained 15% less nitrogen, BN was neutral and did not differ between the regimens. Nitrogen conservation with KA was due to a reduction in urea nitrogen appearance. Rates of WBPT measured during fasting and feeding did not differ between the KA or EAA regimens. During both regimens, feeding decreased protein degradation, whereas protein synthesis was unchanged. Although feeding stimulated leucine oxidation, rates were 50 to 100% lower than reported in CRF patients consuming 0.6 or 1.0 g protein/kg/day. Thus, neutral Bn with the VLPD regimen is achieved by a marked reduction in amino acid oxidation and a postprandial inhibition of protein degradation.

Adaptation, Physiological↗

PubMed1994

Validation of the tracer-balance concept with reference to leucine: 24-h intravenous tracer studies with L-[1-13C]leucine and [15N-15N]urea.

The validity of tracer-derived estimates of whole-body leucine balance was investigated. Seven healthy young adult subjects received an adequate protein diet for 6 d; at 1800 on the last day, L-[1-13C]leucine and [15N-15N]urea were given as primed, continuous intravenous infusions for 24 h. Subjects were in a fasting state for the first 12 h and at 0600 on day 7 they then received hourly 10 equal meals to achieve a fed state. Total leucine intake (diet plus tracer) was 89.4 mg.kg-1.d-1. Mean daily leucine oxidation was equivalent to 89.5 +/- 3.3 mg leucine/kg. The predicted daily oxidation rate, from measurements made during the last hour of the fast and the fifth hour of the fed period, was 91.2 +/- 5.8 mg/kg (P = 0.25 from measured). Measured and predicted whole-body leucine balances were 0.76 +/- 2.99 and -0.98 +/- 5.54 mg/kg, respectively (P = 0.25). Urea production exceeded urea excretion by 20%; daily protein oxidation was the same when estimated from leucine oxidation or nitrogen excretion. Thus, the tracer-balance concept is valid, and reliable predictions of total daily leucine oxidation and whole-body leucine balance can be obtained from short-term measurements of leucine oxidation during fasted and fed states.

Adult↗

PubMed1994

The 24-h pattern and rate of leucine oxidation, with particular reference to tracer estimates of leucine requirements in healthy adults.

Daily leucine oxidation and derived values for whole-body leucine balance, obtained by continuous measurement throughout a 24-h period, were compared with those predicted from short-term measurements during fasted and fed states in five healthy adults studied during two 6-d experimental diet periods, each immediately followed by a 24-h continuous intravenous tracer infusion of L-[1-13C]leucine. Leucine intake was either 14 or 38.3 mg.kg-1.d-1. Mean measured daily leucine oxidation (mg leucine.kg-1.d-1) was 27.8 and 45.2 for the 14- and 38.3-mg intakes, respectively. Oxidation rates predicted by extrapolation of rates measured during the final hour of fasting (15 h after last meal) and the 5th h of feeding were approximately 12% higher (P < 0.01) than measured rates for both diets. For the prediction based on the 12th h of fasting and 5th h of feeding, it was 4% higher or 0.4% lower than measured rates for the 38.3- and 14- mg intakes, respectively. Hence, relatively small differences exist between measured vs predicted estimates of daily leucine oxidation and balance. These studies support previous conclusions that the current, international requirement value for leucine in healthy adults is far too low.

Adult↗

PubMed1994

Plant proteins in relation to human protein and amino acid nutrition.

Plant protein foods contribute approximately 65% of the per capita supply of protein on a worldwide basis and approximately 32% in the North American region. These sources of protein are discussed in relation to their amino acid content, human amino acid requirements, and dietary protein quality. Mixtures of plant proteins can serve as a complete and well-balanced source of amino acids for meeting human physiological requirements. This short review ends with a list of series of myths and realities concerning the relationship between plant protein and human nutrition and a list of some nutritional issues of concern to the health professional and informed consumer.

Amino Acids↗

PubMed1994

Source and amount of dietary nonspecific nitrogen in relation to whole-body leucine, phenylalanine, and tyrosine kinetics in young men.

We studied the effects of amount and source of nonspecific nitrogen (NSN) on the oxidation of leucine and hydroxylation of phenylalanine. In phase 1, seven adult males received for 6 d diets providing indispensable amino acid intakes to meet the 1985 FAO/WHO/UNU (FAO) requirements or our proposed requirement values (MIT). During one diet period with each diet, the NSN of the basal diets (total nitrogen intake: 107 mg N.kg-1.d-1) was increased to a total of 160 mg N.kg-1.d-1. On the morning of day 7, an 8-h constant intravenous tracer-infusion protocol (3-h fast; 5-h fed state) was conducted with L-[1-13C]leucine, L-[ring-2H5]phenylalanine, and L-[3,3,2H2]-tyrosine as tracers. In phase 2, six subjects were given three diets for 6 d, supplying 107 mg N.kg-1.d-1; NSN was a mixture of dispensable amino acids in which glutamine accounted for 0%, 12.5%, and 100% of total NSN. Leucine oxidation and phenylalanine hydroxylation rates and whole-body leucine and phenylalanine balances were unaffected by addition of supplemental NSN to the diets in phase 1 or by amino acid source of NSN in phase 2. Leucine and phenylalanine balances were lower (P < 0.05) for FAO compared with MIT diets.

Adult↗

PubMed1994

Phenylalanine and tyrosine kinetics for different patterns and indispensable amino acid intakes in adult humans.

In a previous paper (Am J Clin Nutr 1993;58:670-83) we described results for plasma amino acid changes, leucine kinetics, and body leucine and nitrogen balance in 20 young men receiving diets for 3 wk. The diets were based on the 1985 FAO/WHO/UNU amino acid requirement pattern (modified FAO diet; n = 7), the Massachusetts Institute of Technology (MIT) requirement pattern (MIT diet; n = 7), or the egg-protein pattern (Egg diet; n = 6). It was concluded, in comparison with the MIT and Egg diets, that the modified FAO diet was not capable of maintaining body amino acid homeostasis or balance. Here we report results from tracer studies with L-[O-2H5]phenylalanine and [2H2]tyrosine that were carried out within the same experiment. The modified FAO diet failed to maintain a mean body phenylalanine balance as determined from rates of phenylalanine hydroxylation (corrected for deuterium-isotopekinetic effects); balance was achieved with the MIT and Egg diets. These results further underscore the inadequacy of the internationally proposed amino acid requirement pattern for healthy adults. We recommend interim use of the MIT, tentative amino acid requirement values in all considerations of adult human amino acid requirements and nutrition.

Adult↗

PubMed1994

Increased energy requirements and changes in body composition with resistance training in older adults.

Body composition and the components of energy metabolism were examined in 12 men and women, aged 56-80 y, before and after 12 wk of resistance training. Subjects were randomly assigned to groups that consumed diets that providing either 0.8 or 1.6 g protein.kg-1.d-1 and adequate total energy to maintain baseline body weight. Fat mass decreased 1.8 +/- 0.4 kg (P < 0.001) and fat-free mass (FFM) increased 1.4 +/- 0.4 kg (P < 0.01) in these weight-stable subjects. The increase in FFM was associated with a 1.6 +/- 0.4 kg increase in total body water (P < 0.01) but no significant change in either protein plus mineral mass or body cell mass. With resistance training, the mean energy intake required for body weight maintenance increased by approximately 15%. Increased energy expenditure included increased resting metabolic rate (P < 0.02) and the energy cost of resistance exercise. Dietary protein intake did not influence these results. Resistance training is an effective way to increase energy requirements, decrease body-fat mass, and maintain metabolically active tissue mass in healthy older people and may be useful as an adjunct to weight-control programs for older adults.

Adipose Tissue↗

PubMed1994

Plasma proline and leucine kinetics: response to 4 wk with proline-free diets in young adults.

The effects of removing proline from the diet on plasma leucine and proline kinetics were investigated. After a 1-wk control period, during which young adult men received a diet containing a complete L-amino acid mixture, seven subjects were given for 4 wk a diet devoid of proline (group 1); six received a diet devoid of proline, arginine, aspartate, glutamate, and serine (group 2); and seven continued with the complete diet (group 3). At the end of the control and 4-wk periods subjects were given a continuous, (3-h fast, 5-h fed) intravenous infusion of L-[1-13C]leucine and L-[5,5-2H]proline. Plasma proline was reduced significantly, especially during the fed state, in groups 1 and 2 after the 4-wk diet periods. Small but statistically significant (P < 0.05) reductions occurred in nonoxidative leucine disappearance and leucine appearance during the fasted state in group 2. Proline fluxes decreased by approximately 50% in fasted and fed states in groups 1 and 2. Mean de novo proline synthesis during the fasted state declined markedly (P < 0.05) after 4 wk in groups 1 and 2.

Adult↗

PubMed1994

Increased protein requirements in elderly people: new data and retrospective reassessments.

Dietary protein requirements of elderly people were determined by short-term nitrogen-balance techniques and using calculations recommended by the 1985 Joint FAO/WHO/UNU Expert Consultation. Twelve men and women aged 56-80 y were randomly assigned to groups that consumed either 0.80 +/- 0.01 or 1.62 +/- 0.02 g protein.kg-1.d-1 (mean +/- SEM). Net nitrogen balance was negative for the lower-protein group (-4.6 +/- 3.4 mg N.kg-1.d-1) and positive for the higher-protein group (13.6 +/- 1.0 mg N.kg-1.d-1); the intake required for nitrogen equilibrium was estimated to be 1.00 g.kg-1.d-1. Nitrogen-balance data from three previous protein requirement studies in elderly people were recalculated by using the same balance formula and combined with the current study data to provide an overall weighted mean protein requirement estimate of 0.91 +/- 0.043 g.kg-1.d-1. Together, the current and retrospective nitrogen-balance data suggest that the mean protein requirement in elderly adults is considerably greater than the 0.60 g.kg-1.d-1 established by the 1985 Joint FAO/WHO/UNU Expert Consultation. A safe protein intake for elderly adults would be 1.0-1.25 g.kg-1.d-1 of high-quality protein.

Aged↗

PubMed1994

Methionine and cysteine kinetics at different intakes of cystine in healthy adult men.

We investigated plasma methionine and cysteine kinetics in eight healthy adult men receiving for 6 d each of five L-amino acid diets supplying 13 mg methionine.kg-1.d-1 without cystine or 6.5 mg methionine.kg-1.d-1 plus 0, 5.2, 10.5, or 20.9 mg cystine.kg-1.d-1. On the morning of day 7, primed, constant intravenous infusions of L-[2H3-methyl, 1-13C]methionine and L-[3,3-2H]cysteine were given for 8 h (for the first 3 h subjects remained in a fasted state and for the next 5 h received small, equal meals at hourly intervals to achieve a fed state). Methionine and cysteine fluxes and rate of methionine oxidation were estimated from plasma methionine and cysteine labeling and 13C in expired air. Methionine oxidation declined (P < 0.05) with lowered methionine intake. Cysteine flux was similar across diets and dietary cystine did not affect tracer methionine oxidation. If there is a sparing effect of dietary cystine on the methionine requirement in adults, it probably takes place during the "first-pass" removal of these amino acids within the splanchnic region.

Adult↗

PubMed1994

Similar 24-h pattern and rate of carbon dioxide production, by indirect calorimetry vs. stable isotope dilution, in healthy adults under standardized metabolic conditions.

We investigated the applicability of the bicarbonate stable isotope dilution technique for accurate determination of 24-h energy expenditure in humans and in reference to the conduct of short-term (< or = 8 h) metabolic studies. Five healthy adult subjects consumed for 4 d a standard diet providing approximately 188 kJ.kg-1.d-1 and 1.0 g.kg-1.d-1 of egg protein. From d 4 at 1800 h to d 5 at 1800 h, a 24-h metabolic study, combining indirect calorimetry with an intravenous infusion of 13C-labeled sodium bicarbonate, was performed under standardized conditions of 12 h fasting-12 h feeding. "Measured" CO2 production (VCO2) (indirect calorimetry) over 24 h was not significantly different from "predicted" VCO2 (bicarbonate dilution) (218.31 +/- 20.91 vs. 221.51 +/- 19.44 mmol CO2.kg-1.d-1, respectively) (P = 0.34). Further, 24-h VCO2 and energy expenditure were determined by extrapolating from "predicted" VCO2 during the last hour of fasting (15th hour following last meal) and the fifth hour of the small hourly meal-feeding phase. The maximum difference for an individual subject between the above-calculated 24-h energy expenditure and that from 24-h indirect calorimetry measurements was < 4%. These results support use of the present experimental protocol, and the bicarbonate dilution technique, lasting < or = 8 h, to obtain reliable quantitative estimates of 24-h CO2 production and energy expenditure in healthy adult humans.

Adult↗

PubMed1994

Adult amino acid requirements: the case for a major revision in current recommendations.

This is a brief review about the current state of knowledge concerning the minimum physiological requirements for indispensable amino acids in healthy adult humans. It is hypothesized that current international estimations of these requirements are far too low, except for the sulfur-containing amino acids. Stable isotope tracer studies of amino acid kinetics are described, and that it is concluded that they support this hypothesis. Tentative revised estimates of requirements are presented.

Adult↗

PubMed1994

Phenylalanine and tyrosine kinetics in critically ill children with sepsis.

To better understand the impact of severe illness on the amino acid economy and nutritional needs of pediatric patients, we studied plasma phenylalanine and tyrosine kinetics in eleven critically ill patients (six full-term newborns and five young infants). Within 48 h of the diagnosis of sepsis they were given primed constant i.v. infusions of L-[1-13C]phenylalanine and L-[3,3,2H2]tyrosine for 4 h. Routine nutritional support continued during this period by parenteral administration of dextrose, lipid emulsion, and an amino acid mixture low in tyrosine. Phenylalanine and tyrosine fluxes and rate of phenylalanine hydroxylation did not differ significantly between the two age groups, and so the data were combined for evaluation. For the entire group, values (mumol.kg-1.h-1; mean +/- SD) for phenylalanine and tyrosine fluxes and rate of phenylalanine hydroxylation were 132 +/- 24, 66 +/- 16, and 29 +/- 12, respectively. Plasma phenylalanine to tyrosine concentration ratio was 1.67 +/- 0.6. From a comparison of the rate of phenylalanine hydroxylation with measured phenylalanine intakes, it was concluded that their routine, clinical nutritional support was inadequate to achieve body phenylalanine balance. In comparison with published data, the relative rate of phenylalanine hydroxylation appears to be high. We speculate that tyrosine is a conditionally indispensable amino acid under these conditions; it would be desirable to establish the intake levels and ratio of phenylalanine to tyrosine that effectively support aromatic amino acid balance in these critically ill patients.

Bacterial Infections↗

PubMed1993

Plasma arginine and citrulline kinetics in adults given adequate and arginine-free diets.

The fluxes of arginine and citrulline through plasma and the rate of conversion of labeled citrulline to arginine were estimated in two pilot studies (with a total of six adult subjects) and in a dietary study with five healthy young men. These latter subjects received an L-amino acid-based diet that was arginine-rich or arginine-free each for 6 days prior to conduct, on day 7, of an 8-hr (first 3 hr, fast; final 5 hr, fed) primed continuous intravenous infusion protocol using L-[guanidino-13C]arginine, L-[5,5-2H2]citrulline, and L-[5,5,5-2H3]leucine, as tracers. A pilot study indicated that citrulline flux was about 20% higher (P < 0.05) when determined with [ureido-13C]citrulline compared with [2H2]citrulline, indicating recycling of the latter tracer. Mean citrulline fluxes were about 8-11 mumol.kg-1.hr-1 for the various metabolic/diet groups and did not differ significantly between fast and fed states or arginine-rich and arginine-free periods. Arginine fluxes (mean +/- SD) were 60.2 +/- 5.4 and 73.3 +/- 13.9 mumol.kg-1.hr-1 for fast and fed states during the arginine-rich period, respectively, and were significantly lowered (P < 0.05), by 20-40%, during the arginine-free period, especially for the fed state, where this was due largely to reduced entry of dietary arginine into plasma. The conversion of plasma citrulline to arginine approximated 5.5 mumol.kg-1.hr-1 for the various groups and also was unaffected by arginine intake. Thus, endogenous arginine synthesis is not markedly responsive to acute alterations in arginine intake in healthy adults. We propose that arginine homeostasis is achieved largely via modulating arginine intake and/or the net rate of arginine degradation.

Adult↗

PubMed1993

Splanchnic metabolism of dietary arginine in relation to nitric oxide synthesis in normal adult man.

Urinary nitrate (NO3) is the stable end product of nitric oxide, which is formed, in turn, from a guanidino nitrogen of arginine. We have conducted two experiments, each in four healthy adult men receiving a low nitrate diet for 7-10 days, to investigate the in vivo conversion of arginine to nitrate. In the first study [guanidino-15N2, 5,5-2H2]arginine was given on day 7 via a primed continuous intravenous infusion for 8 h. In the second study, the labeled arginine was given for 8 h by the intragastric route on day 7 and by the intravenous route on day 10. Measurement of 15NO3 output in urine collected for 24 h beginning at the time of the arginine tracer infusion revealed a more extensive transfer of 15N when the arginine tracer was given intragastricly. From the comparative labeling of 15NO3 after administration of the tracer arginine via the intragastric and intravenous routes, we estimate that 16% +/- 2% of the daily production of nitrate arises from the metabolism of dietary arginine that is taken up during its "first pass" in the splanchnic region. Hence, nitric oxide production occurs, to a measurable extent, in this area in healthy subjects, raising the question as to how various pathophysiological states might alter the relations between exogenous and endogenous sources of arginine as precursors of NO. and the relative contributions made by various organs to whole body (NO.) NO3 formation. These results also raise important questions about the use of nitric oxide synthase inhibitors in animal and human studies.

Adult↗