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Biomedical subjects

C Persaud

Publications and source records attributed to C Persaud.

At least 19 recordsLinked to original sources

Training does not affect protein turnover in pre- and early pubertal female gymnasts.

This study compared protein turnover in ten young female gymnasts [10.3 (0.5) years] engaged in regular intense physical training with ten age-matched controls [9.4 (0.6) years)]. Nitrogen flux ( Q), protein synthesis (PS), protein degradation (PD) and net protein turnover (NPB = PS-PD) were measured following a single oral dose of [(15)N]-glycine. The habitual dietary intake of each subject was assessed using a 7-day food record, with food portions being weighed before ingestion. The gymnasts had a low total energy intake which was unbalanced in the proportions of lipid, carbohydrate and protein. Protein flux was 7.19 (0.35) g.kg(-1).day(-1) in the gymnasts and 7.53 (0.81) g.kg(-1).day(-1) in the controls; protein synthesis was 6.06 (0.27) g.kg(-1).day(-1 )in the gymnasts and 6.53 (0.74) g.kg(-1).day(-1) in the controls; protein degradation was 5.45 (0.38) g.kg(-1).day(-1) in the gymnasts and 5.27 (0.74) g.kg(-1).day(-1) in the controls. All data are presented as means and standard errors of the mean (SEM). There were no statistical differences for protein flux, protein synthesis or protein degradation between the two groups. However, NPB was lower (-14%) in the trained gymnasts than in the control group ( P <0.05), which might be explained by a greater protein ingestion in the control group on the day of the protocol ( P <0.05). These results show that in pre- and early pubertal female gymnasts intense training does not exert a demonstrable effect on protein turnover.

Child↗

An international survey of unrelated umbilical cord blood banking.

OBJECTIVES: To investigate operational and technical practices within the field of cord blood banking. MATERIALS AND METHODS: Cord blood banks world-wide were invited to participate in a survey of collection, processing and testing. The survey covered a 12-month period up to August 1998. RESULTS: Replies were received from 18 cord blood banks. Analysis of the survey responses demonstrated wide variations in many aspects of cord blood banking. CONCLUSION: There is a need for standardization to ensure adoption of best practice.

Blood Banks↗

The transfer of 15N from urea to lysine in the human infant.

To explore the nutritional significance of urea hydrolysis for human subjects, male infants being treated for severe undernutrition were given oral doses of 10 mg [15N15N]urea every 3 h for 36 h, on admission, during rapid growth and after repletion with either moderate or generous intakes of protein. Urea hydrolysis was calculated from the 15N enrichment of urinary urea, and where possible, lysine, alanine, glycine and histidine were isolated from urine by preparative ion-exchange chromatography for measurement of 15N enrichment. Sufficient N was obtained for 15N enrichment of lysine to be measured on fifteen occasions from six children. Urea hydrolysis accounted for half of all urea production with 130 (SD 85) mg N/kg hydrolysed per d, most of which appeared to be utilized in synthetic pathways. Of the samples analysed successfully, nine samples of lysine were enriched with 15N (mean atom percent excess 0.0102, range 0.0017-0.0208) with relative enrichment ratios with respect to lysine of 1.63 (range 0.18-3.15), 1.96 (range 0.7-3.73) and 0.9 (range 0.4-1.8) for glycine, alanine and histidine respectively. Enriched samples were identified at each treatment phase and 68% of the variation in lysine enrichment was explained by the variation in urea enrichment with 54% explained by the overall rate of delivery of 15N to the lower gastrointestinal tract. The results indicate a minimum of 4.7 mg lysine per kg body weight made available by de novo synthesis with the more likely value an order of magnitude higher. Thus, urea hydrolysis can improve the quality of the dietary protein supply by enabling an increased supply of lysine and other indispensable amino acids.

Alanine↗

Dietary protein, growth and urea kinetics in severely malnourished children and during recovery.

The case mortality for severe malnutrition in childhood remains high, but established best approaches to treatment are not used in practice. The energy and protein content of the diet at different stages of treatment appears important, but remains controversial. The effect on growth, urea kinetics and the urinary excretion of 5-L-oxoproline was compared between a standard infant formula (HP group) provided in different quantities at each stage of treatment and a recommended dietary regimen, which differentiates the requirements of protein and energy during the acute phase of resuscitation (maintenance intake of energy and protein, relatively low protein to energy ratio, LP group) from those during the restoration of a weight deficit (energy and nutrient dense). The energy required to maintain weight was less in the HP than the LP group, but the HP group was not able to achieve as high an energy intake during repletion of wasting because of the high volume which would have had to be consumed. Compared to the LP group, in the HP group during catch-up growth there was significantly greater deposition of lean tissue and higher rates of urea production, hydrolysis and salvage of urea-nitrogen. These, together with higher rates of 5-L-oxoprolinuria, suggest a greater constraint of the formation of adequate amounts of nonessential amino acids, especially glycine, in the face of enhanced demands. Although more effective rehabilitation might be achieved using a standard formula, there is the need to determine the extent to which it might impose metabolic stress compared with the modified formulation.

Diet↗

Infants in Trinidad excrete more 5-L-oxoproline (L-pyroglutamic acid) in urine than infants in England: an environmental not ethnic difference.

The demand for glycine to satisfy normal growth during early life is considerable and most has to be made endogenously. The extent to which adequate glycine is available can be assessed by measuring the urinary excretion of 5-L-oxoproline. The excretion of 5-L-oxoproline at 6 weeks of age for infants in Trinidad of African, Indian or mixed parentage (398 mumol/mmol creatinine) was significantly greater than for infants born in England of Caucasian parentage (194 mumol/mmol creatinine). There was no relationship between 5-L-oxoproline excretion and either sex or pattern of feeding. There were significant inverse relationships between 5-L-oxoproline/creatinine and birth weight, and head circumference either at birth or 6 weeks of age, suggesting that limited availability of glycine is associated with poorer growth before and after birth. For a group of infants born in England of Indian parentage, excretion of 5-L-oxoproline (155 mumol/mmol creatinine) was not different to infants of Caucasian parentage, but significantly less than infants born in Trinidad. The demonstration that 5-L-oxoproline/creatinine was similar in infants born in England, regardless of parentage, shows that the differences between England and Trinidad are related to environment and are unlikely to be accounted for by genetic differences or ethnicity.

Africa↗

Dietary supplementation with L-methionine impairs the utilization of urea-nitrogen and increases 5-L-oxoprolinuria in normal women consuming a low protein diet.

Urea kinetics were measured in normal women after 5 d consuming a low protein diet [LP, 67 mg N/(kg.d), 0.42 g protein/(kg.d)]. To determine whether the availability of methionine limits the utilization of nonessential nitrogen from low protein diets, the study was repeated on four further occasions with the addition of dietary supplements of L-methionine, 9 mg N/(kg.d) (LP-M); urea, 52 mg N/(kg.d) (LP-U); urea and methionine (LP-UM); or urea, 26 mg N/(kg.d), and glycine, 26 mg N/(kg.d), (LP-UG). Urea kinetics were derived after prime and intermittent oral doses of [15N15N]urea from the measurements of enrichment by isotope ratio mass spectrometry in urea isolated from urine. Nitrogen balance was significantly improved when the women consumed LP-U and LP-UG, but not LP-M or LP-UM. The urinary excretion of 5-L-oxoproline was measured as a marker of glycine availability and was significantly lower when women consumed LP-U and LP-UG compared with either LP or LP-M and LP-UM. There was a significant correlation between urinary 5-L-oxoproline and urinary sulfate excretion (r = 0.68, P = 0.00003). The availability of methionine was not limiting for nitrogen metabolism when women consumed these diets, whereas the response to supplementation with urea alone or urea with glycine showed that the availability of nonessential nitrogen was limiting. Glycine is consumed in the detoxification of excess methionine, and supplementation with methionine appeared to place a competitive demand on the availability of glycine for other metabolic processes.

Adult↗

Urea kinetics varies in Jamaican women and men in relation to adiposity, lean body mass and protein intake.

OBJECTIVE: We have measured urea kinetics in normal adult men and women of different body composition to determine whether adiposity is associated with differences in the rate of urea production or endogenous urea hydrolysis. DESIGN: Urea kinetics were determined from the excretion of [15N15N]urea in urine over a period of 48 h following a single oral dose of [15N15N]urea, in nine lean and nine obese women and in seven light and seven heavy males while they were consuming their habitual diets. Urinary 5-L-oxoproline was measured as an index of glycine metabolic status. SETTING: The studies were carried out in the research ward of the Tropical Metabolism Research Unit, University of the West Indies. RESULTS: Successful studies were completed in eight obese and five lean women and in six heavy and five light men. When compared with lean women, in obese women the rate of urea production and hydrolysis was significantly greater and this difference could not be accounted for by the greater fat-free mass alone, and was in part associated directly with the increase in fat mass. The rate of urea production and hydrolysis was greater in heavy men than in light men, a difference which was attributed to an increase in dietary protein. In obese women and heavy men there was a significantly higher rate of excretion of 5-L-oxoproline in urine when compared with lean women and lean men respectively. CONCLUSION: This paper highlights the difficulty in identifying an appropriate reference with which to express results in people of different body composition. In obese women urea production and the hydrolysis of urea are increased, in part related to the increased fat-free mass, but also related to the increased fat mass itself. In obese women and men on high protein diets the greater rate of hydrolysis urea may be a reflection of an increased demand for the synthesis of non-essential amino acids, especially glycine.

Adult↗

Urinary 5-L-oxoproline (pyroglutamic acid) excretion is greater in infants in Jamaica than in infants in England.

OBJECTIVE: To determine the pattern of excretion in urine of 5-L-oxoproline, as a measure of glycine status, during the first six weeks of life in Jamaican infants. DESIGN: Spot samples of urine were collected from term and preterm infants at birth and longitudinally to four weeks of age, or at six weeks of age. 5-L-oxoproline was isolated by column chromatography and hydrolysed to L-glutamic acid, which was measured enzymatically and the results expressed relative to creatinine excretion. SETTING: Maternity wards and postnatal clinic of the University Hospital of the West Indies. SUBJECTS: African-Caribbean infants, 19 term and 21 preterm, from birth to four weeks of age, and 79 term infants at six weeks of age. RESULTS: There were no differences between term and preterm infants. Excretion of 5-L-oxoproline increased progressively from birth, 141 mumol/mmol creatinine, to 270 mumol/mmol creatinine at four weeks of age. At six weeks of age, excretion was significantly greater than at birth or four weeks of age, 525 mumol/mmol creatinine. Compared with infants born in England, the excretion of 5-L-oxoproline was not different at birth, but was significantly greater in Jamaican infants at six weeks of age. CONCLUSIONS: Glycine status, indicated by increased excretion of 5-L-oxoproline, is marginal in Jamaican infants at six weeks of age, and this possibly reflects a limitation in the endogenous biosynthesis of glycine due to a dietary limitation of folate or vitamin B-12.

Chromatography↗

Urea kinetics in healthy women during normal pregnancy.

Urea kinetics were measured in normal women aged 22-34 years at weeks 16, 24 and 32 on either their habitual protein intake (HABIT) or a controlled intake of 60 g protein/d (CONTROL), using primed-intermittent oral doses of [15N15N]urea and measurement of plateau enrichment in urinary urea over 18 h (ID) or a single oral dose of [15N15N]urea and measurement of enrichment of urea in urine over the following 48 h (SD). The intake of protein during HABIT-ID (80 g/d) was greater than that on HABIT-SD (71 g/d); urea production as a percentage of intake was significantly greater at week 16 for HABIT-ID than HABIT-SD, whereas urea hydrolysis at week 16 was greater for HABIT-SD than HABIT-ID and urea excretion at week 32 was greater for HABIT-ID than HABIT-SD. The combined results for HABIT-ID and HABIT-SD showed a significant reduction in urea production at week 32 compared with week 24. Urea excretion decreased significantly from week 16 to week 24 with no further decrease to week 32 and urea hydrolysis was significantly greater at week 24 than either week 16 or week 32. Compared with HABIT, on CONTROL there was a decrease in urea production at week 16, and urea excretion was significantly reduced at week 16. For all time periods urea production was closely related to the sum of intake plus hydrolysis. Hydrolysis was greatest at week 24 and closely related to urea production. There was a significant inverse linear relationship overall for hydrolysis as a proportion of production and excretion as a proportion of intake. The results show that on HABIT N is more effectively conserved in mid-pregnancy through an increase in urea hydrolysis and salvage, and during late pregnancy through a reduction in urea formation. Lowering protein intake at any stage of pregnancy increased the hydrolysis and salvage of urea. The staging of these changes was later than that in pregnancy in Jamaica.

Adult↗

Comparison of urinary 5-L-oxoproline (L-pyroglutamate) during normal pregnancy in women in England and Jamaica.

Urinary 5-L-oxoproline was measured during normal pregnancies in Southampton, England and Kingston, Jamaica. The CV of 5-L-oxoproline excretion in urine, determined over 7 d in a non-pregnant woman and three pregnant women, was 10-36%. Compared with non-pregnant women, urinary 5-L-oxoproline increased three to four times from early pregnancy in women in Southampton, a highly significant difference, and remained elevated at similar levels during mid and late pregnancy. For women in Kingston, the excretion of 5-L-oxoproline was similar to that of Southampton women in the non-pregnant group and during early pregnancy. However, there was a progressive increase in the excretion of 5-L-oxoproline as pregnancy advanced and by late pregnancy excretion was from three to ten times greater than the average for the non-pregnant women. There was a significant difference between the women in Southampton and the women in Kingston during mid and late pregnancy, with women in Kingston excreting twice as much 5-L-oxoproline during late pregnancy. If the excretion of 5-L-oxoproline is a measure of glycine insufficiency, the results would indicate that in some pregnancies the ability of the mother to provide glycine for herself and the developing fetus is marginal or inadequate and the constraint appears more marked in Jamaica than in England.

Adult↗

Urinary excretion of 5-L-oxoproline (pyroglutamic acid) during early life in term and preterm infants.

Urinary 5-L-oxoproline was measured in term and preterm infants from shortly after birth until 6 weeks of postnatal age to determine their ability to synthesise glycine. In term infants the excretion was five to 10 times that seen in normal adults, increasing from 105 mumol/mmol creatinine in the first 72 hours after birth to 170 mumol/mmol creatinine at 6 weeks of age. There was a significant inverse linear correlation between the excretion of 5-L-oxoproline and length of gestation or birthweight. By 6 weeks of age there was no longer a significant difference in 5-L-oxoproline between term and preterm infants. There was no difference in the excretion of 5-L-oxoproline between boys and girls, or between infants fed on human milk or an artificial formula. If, in part, variability in the excretion of 5-L-oxoproline is determined by the extent to which the endogenous formation of glycine is adequate, then glycine formation may be marginal during early life, more so in preterm than in term infants, providing additional evidence that glycine is a conditionally essential amino acid in the neonate.

Birth Weight↗

Urinary excretion of 5-L-oxoproline (pyroglutamic acid) is increased in normal adults consuming vegetarian or low protein diets.

A method for measuring 5-L-oxoproline in urine, which involves isolation by short-column chromatography, acid hydrolysis to glutamic acid and enzymic assay of glutamic acid, was used to measure the rate of excretion in normal adults, aged 20 to 45 y. There was no difference in the daily excretion between omnivorous males (217 micromol/d) and females (195 micromol/d). In vegetarian males, urinary 5-L-oxoproline (404 micromol/d) was significantly greater than in vegetarian females (267 micromol/d, P = 0.013). Compared with omnivorous males or females, excretion of 5-L-oxoproline was significantly greater in vegetarian males (P < 0.0001) and females (P= 0.005). When normal adults consumed a diet in which the protein content was controlled at either 4.0 or 6.2 g N/d for 5 d, there was a significant increase in urinary 5-L-oxoproline on d 5, compared with either d 1 or 4. There was a significant inverse linear relationship between the increased urinary 5-L-oxoproline on the fifth dietary day and the nitrogen content of the diet. On the basis of this relationship, when the urinary excretion of 5-L-oxoproline (320 micromol/d) for vegetarians was predicted from an estimate of their dietary intake of nitrogen, the estimate was, on average, close to the measured value (345 micromol/d). As a matter of course, vegetarians excrete more 5-L-oxoproline in urine than do omnivores, and we speculated that this difference might be accounted for by differences in dietary nitrogen and the endogenous capacity for de novo synthesis of glycine.

Adult↗

Urinary excretion of 5-L-oxoproline (pyroglutamic acid) is increased during recovery from severe childhood malnutrition and responds to supplemental glycine.

We hypothesized that a limitation in the endogenous formation of glycine might constrain catch-up growth during recovery from severe childhood malnutrition. The urinary excretion of 5-L-oxoproline is increased when the glycine available for glutathione synthesis is limited. Urinary excretion of 5-L-oxoproline was measured throughout recovery in 12 children (aged 16 +/- 6 mo) with severe malnutrition. Urinary 5-L-oxoproline was similar at admission and after recovery, but was increased significantly during rapid catch-up growth. There was a significant relationship between the rate of weight gain and 5-L-oxoproline excretion in urine. In nine children (aged 15 +/- 5 mo), the effect of oral supplementation with glycine, [1.7 mmol/(kg x d) for 48 h] during rapid catch-up growth on 5-L-oxoprolinuria and blood glutathione concentration was determined. In seven of the nine children weight gain was less than 17 g/(kg x d) and following oral glycine supplements 5-L-oxoproline excretion was reduced up to 64% and blood glutathione concentration increased up to 100%. In the two children who were gaining weight at a rate > 17 g/(kg x d), glycine supplementation was associated with a further increase in 5-L-oxoproline excretion and a decrease in blood glutathione. If 5-L-oxoproline is an index of the relative availability of glycine, then the data indicate that glycine may be limiting during rapid catch-up growth. This would have important implications for repletion of muscle and gain in height.

Aging↗

Protein quality and urea kinetics in prepubertal Chilean schoolboys.

Urea kinetics were measured non-invasively in 12 Chilean schoolboys aged 8-10 years who were receiving one of two diets, either predominantly animal protein or predominantly vegetable protein. Both the diets provided an equivalent level of gross protein, 1.2 g/kg/day. The study diets were given for 10 days to enable adaptation to take place. On the eighth day a single oral dose of 15N15N-urea, 100 mg, was given and the amount of label excreted as 15N15-urea in urine over the subsequent 48 hours was measured. There was little difference in any aspect of urea kinetics between the two diets with urea production (animal, 173 +/- 50 mgN/kg/day; vegetable 179 +/- 53 mgN/kg/day), urea excretion (animal, 86 +/- 19 mgN/kg/day; vegetable, 105 +/- 13 mgN/kg/day), urea nitrogen hydrolysis (animal, 87 +/- 49 mgN/kg/day; vegetable, 74 +/- 42 mgN/kg/day), and the salvaged urea-nitrogen derived from hydrolysis which returned to urea formation (animal, 12 +/- 5 mgN/kg/day; vegetable, 17 +/- 9 mgN/kg/day) all being similar. A very high proportion of the salvage nitrogen derived from urea hydrolysis was maintained within the metabolic pool, about 80%, which was equivalent to 0.4 g protein/kg/day. This is the first time urea kinetics have been measured in children of this age and shows that 57% of the ura produced is excreted in urine on average with about 43% of the urea-nitrogen being salvaged for further metabolic interaction. It is concluded that the vegetable based protein diet taken habitually by Chilean children is metabolically equivalent in terms of urea kinetics to a diet based upon animal protein at this level of intake, but that high rates of salvage of urea nitrogen are found on both diets.

Aging↗

Urea production and salvage during pregnancy in normal Jamaican women.

The pattern of aggregate nitrogen demand during pregnancy and the fetal and maternal components are unclear. Excess demand enhances efficiency of nitrogen utilization. Urea salvage contributes to enhanced efficiency. Dietary protein intake, urea production, and salvage of urea nitrogen were measured in eight nonpregnant control subjects, and trimesterly in nine pregnant women. Production was measured after prime-intermittent intravenous doses of [15N 15N]-urea by dilution of label in urinary urea. Dietary protein intake was greater in trimester 1 than in nonpregnant women (167 +/- 36 vs 224 +/- 60 mg N.kg-1.d-1), and increased further in trimester 2 (266 +/- 59 mg N.kg-1.d-1). Urea production was not higher during pregnancy. Despite higher protein intake, urea salvage was higher in pregnancy (40 +/- 24 nonpregnant vs 77 +/- 23, 61 +/- 31, and 51 +/- 12 mg N.kg-1.d-1). Therefore, the demand-supply gap for nitrogen was greatest early in pregnancy when fetoplacental growth is slowest, and implies heightened maternal demand.

Adult↗

Cysteine and glycine supplementation modulate the metabolic response to tumor necrosis factor alpha in rats fed a low protein diet.

Responses to cytokines entail synthesis of substances rich in cysteine and glycine, such as glutathione (GSH), metallothionein and some plasma proteins. To examine the importance of an adequate supply of cysteine and glycine, we fed rats a low protein diet supplemented with L-cysteine and glycine, separately or in combination, or L-alanine, or a high protein diet for 1 wk before injection with tumor necrosis factor alpha (TNF) or saline. The high protein diet-fed group had greater liver weight and zinc and GSH concentrations after TNF than the group fed the low protein diet supplemented with alanine. Glycine and cysteine supplementation resulted in greater liver weight after TNF treatment than did alanine supplementation. Cysteine supplementation had a similar influence on GSH concentration. Ceruloplasmin, alpha-2-macroglobulin and alpha-1-acid glycoprotein were higher in TNF-treated rats than in saline controls in each dietary group. However, feeding supplementary glycine and cysteine and the high protein diet often resulted in different values than seen in animals fed the low protein diet supplemented with alanine. Paradoxically, lower ceruloplasmin concentrations were observed in animals fed the former diets than in those fed the latter. alpha-2-Macroglobulin concentration was lower in all animals fed low protein diets than in those fed the high protein diet. alpha-1-Acid glycoprotein was lowest in groups fed cysteine-supplemented diets and highest in the glycine-supplemented group.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗