Determination of Indispensable Amino Acid Digestibility of the Red Kidney Bean in Humans Using a Dual Stable Isotope Tracer Method.

BACKGROUND: Protein quality of the red kidney bean (RKB), a common source of dietary protein, has been assessed using the protein digestibility-corrected amino acid score (PDCAAS) determined in animal models using mainly oro-fecal digestibility. More recently, the FAO recommended to use digestible indispensable amino acid score (DIAAS) instead of PDCAAS but highlighted insufficient data on true ileal indispensable amino acid (IAA) digestibility of proteins because amino acids are absorbed in the ileum. OBJECTIVES: Using a recently developed dual stable isotope tracer method, we aimed to measure each IAA digestibility as representation of true ileal digestibility of the RKB, Phaseolus vulgaris, in humans consuming a typical Jamaican meal. METHODS: RKB-IAAs were intrinsically labeled by adding 2H2O to the plants. Uniformly labeled-[13C]-spirulina (standard protein) was added to a meal prepared with the labeled RKB and fed to 10 healthy adults (5 males, 5 females) in a nonrandomized trial as primed/intermittent doses to achieve a steady state IAA enrichment in plasma. Enrichment of 2H- and 13C-labeled IAA in plasma and the bean was measured by mass spectrometry. Each IAA digestibility (except tryptophan and histidine) was calculated as the ratio of plasma 2H-IAA to meal 2H-IAA divided by the ratio of plasma 13C-IAA to meal 13C-IAA adjusted for loss of 2H-atom during transamination and digestibility of spirulina. RESULTS: Adequate IAA labeling (>1000 ppm 2H excess) and plasma plateau isotopic enrichment were achieved. Mean RKB-IAA digestibility (%) was 79.4 ± 0.5, ranging from 69.0 ± 1.2 (threonine) to 85.7 ± 1.7 (lysine). CONCLUSION: The dual stable isotope tracer digestibility data are similar to published oro-fecal digestibility supporting substantial nitrogen exchange in the colon. The individual IAA digestibility is useful to derive DIAAS to replace PDCAAS. Using published RKB-IAA composition, extrapolated DIAAS was 0.63 based on the lowest score for methionine. CLINICAL TRIAL REGISTRATION: https://register. CLINICALTRIALS: gov; ID: NCT-04118517.

Glutathione metabolism in type 2 diabetes and its relationship with microvascular complications and glycemia.

AIMS/HYPOTHESES: We hypothesized that there is decreased synthesis of glutathione (GSH) in type 2 diabetes (T2DM) especially in the presence of microvascular complications, and this is dependent on the degree of hyperglycemia. METHODS: In this case-control study, we recruited 16 patients with T2DM (7 without and 9 with microvascular complications), and 8 age- and sex-matched non-diabetic controls. We measured GSH synthesis rate using an infusion of [2H2]-glycine as isotopic tracer and collection of blood samples for liquid chromatography mass spectrometric analysis. RESULTS: Compared to the controls, T2DM patients had lower erythrocyte GSH concentrations (0.90 ± 0.42 vs. 0.35 ± 0.30 mmol/L; P = 0.001) and absolute synthesis rates (1.03 ± 0.55 vs. 0.50 ± 0.69 mmol/L/day; P = 0.01), but not fractional synthesis rates (114 ± 45 vs. 143 ± 82%/day; P = 0.07). The magnitudes of changes in patients with complications were greater for both GSH concentrations and absolute synthesis rates (P-values ≤ 0.01) compared to controls. There were no differences in GSH concentrations and synthesis rates between T2DM patients with and without complications (P-values > 0.1). Fasting glucose and HbA1c did not correlate with GSH concentration or synthesis rates (P-values > 0.17). CONCLUSIONS: Compared to non-diabetic controls, patients with T2DM have glutathione deficiency, especially if they have microvascular complications. This is probably due to reduced synthesis and increased irreversible utilization by non-glycemic mechanisms.

EXpanding Treatment for Existing Neurological Disease (EXTEND): An Open-Label Phase II Clinical Trial of Hydroxyurea Treatment in Sickle Cell Anemia.

BACKGROUND: Cerebral vasculopathy in sickle cell anemia (SCA) begins in childhood and features intracranial arterial stenosis with high risk of ischemic stroke. Stroke risk can be reduced by transcranial doppler (TCD) screening and chronic transfusion therapy; however, this approach is impractical in many developing countries. Accumulating evidence supports the use of hydroxyurea for the prevention and treatment of cerebrovascular disease in children with SCA. Recently we reported that hydroxyurea significantly reduced the conversion from conditional TCD velocities to abnormal velocities; whether hydroxyurea can be used for children with newly diagnosed severe cerebrovascular disease in place of starting transfusion therapy remains unknown. OBJECTIVE: The primary objective of the EXpanding Treatment for Existing Neurological Disease (EXTEND) trial is to investigate the effect of open label hydroxyurea on the maximum time-averaged mean velocity (TAMV) after 18 months of treatment compared to the pre-treatment value. Secondary objectives include the effects of hydroxyurea on serial TCD velocities, the incidence of neurological and non-neurological events, quality of life (QOL), body composition and metabolism, toxicity and treatment response, changes to brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), genetic and serologic markers of disease severity, and cognitive and pulmonary function. METHODS: This prospective Phase II trial will enroll children with SCA in Jamaica, between the ages of 2 and 17 years, with either conditional (170-199 cm/sec) or abnormal (≥ 200 cm/sec) TCD velocities. Oral hydroxyurea will be administered daily and escalated to the maximum tolerated dose (MTD). Participants will be seen in the Sickle Cell Unit (SCU) in Kingston, Jamaica monthly until achieving MTD, and then every 3 months. TCD will be performed every 6 months. RESULTS: Currently, 43 participants have been enrolled out of a projected 50. There was one withdrawal due to immigration, with no permanent screen failures. Of the 43 enrolled, 37 participants have initiated study treatment. CONCLUSIONS: This trial investigates the effects of hydroxyurea treatment at MTD in children with conditional or abnormal TCD velocities before transfusion therapy and may represent an important advance towards establishing a suitable non-transfusion protocol for stroke prevention in children with SCA. The trial outcomes will have profound significance in developing countries where the disease burden is highest. CLINICALTRIAL: ClinicalTrials.gov NCT02556099; https://clinicaltrials.gov/ct2/show/NCT02556099 (Archived by WebCite at http://www.webcitation.org/6k1yMAa9G).

Developmental contributions to macronutrient selection: a randomized controlled trial in adult survivors of malnutrition.

BACKGROUND AND OBJECTIVES: Birthweight differences between kwashiorkor and marasmus suggest that intrauterine factors influence the development of these syndromes of malnutrition and may modulate risk of obesity through dietary intake. We tested the hypotheses that the target protein intake in adulthood is associated with birthweight, and that protein leveraging to maintain this target protein intake would influence energy intake (EI) and body weight in adult survivors of malnutrition. METHODOLOGY: Sixty-three adult survivors of marasmus and kwashiorkor could freely compose a diet from foods containing 10, 15 and 25 percentage energy from protein (percentage of energy derived from protein (PEP); Phase 1) for 3 days. Participants were then randomized in Phase 2 (5 days) to diets with PEP fixed at 10%, 15% or 25%. RESULTS: Self-selected PEP was similar in both groups. In the groups combined, selected PEP was 14.7, which differed significantly (P < 0.0001) from the null expectation (16.7%) of no selection. Self-selected PEP was inversely related to birthweight, the effect disappearing after adjusting for sex and current body weight. In Phase 2, PEP correlated inversely with EI (P = 0.002) and weight change from Phase 1 to 2 (P = 0.002). Protein intake increased with increasing PEP, but to a lesser extent than energy increased with decreasing PEP. CONCLUSIONS AND IMPLICATIONS: Macronutrient intakes were not independently related to birthweight or diagnosis. In a free-choice situation (Phase 1), subjects selected a dietary PEP significantly lower than random. Lower PEP diets induce increased energy and decreased protein intake, and are associated with weight gain.

Adaptation of in vivo amino acid kinetics facilitates increased amino acid availability for fetal growth in adolescent and adult pregnancies alike.

During pregnancy, adult women with a normal BMI synthesise extra amino acids after an overnight fast by increasing body protein breakdown and decreasing amino acid oxidation. It is not known whether adolescent girls can make these adaptations during pregnancy. The present study aimed to measure and compare the protein, glutamine and alanine kinetics of adult women and adolescent girls at early-, mid- and late-pregnancy. Kinetics were measured in the overnight fasted state using intravenous infusions of 13C-leucine, 15N-glutamine and 15N-alanine in ten adults and twenty adolescents aged 14-17 years in the first and second trimesters (phase 1 study) and infusions of 13C-leucine and 15N2-urea in ten adults and eleven adolescents aged 16-17 years in the first and third trimesters (phase 2 study). In phase 1 study, there were no significant differences between the groups with regard to any of the kinetic parameters measured. In both groups, leucine flux increased (P< 0.05), the percentage of leucine flux oxidised decreased (P< 0.05) and non-oxidative leucine disposal to protein synthesis increased (P< 0.05) from the first to the second trimester. In phase2 study, leucine flux was significantly slower (P< 0.05) in the adult group than in the adolescent group during both trimesters, and whole-body leucine flux and non-oxidative leucine disposal increased significantly in the adolescent group (P< 0.05, respectively) and were higher in the adult group from the first to the third trimester. These results suggest that similar to their adult counterparts after an overnight fast, adolescent girls with a normal BMI provide extra amino acids required for net protein deposition during pregnancy by increasing protein breakdown and decreasing amino acid oxidation.

Effects of randomized supplementation of methionine or alanine on cysteine and glutathione production during the early phase of treatment of children with edematous malnutrition.

BACKGROUND: We have shown that a low glutathione concentration and synthesis rate in erythrocytes are associated with a shortage of protein-derived cysteine in children with edematous severe acute malnutrition (SAM). OBJECTIVE: We tested the hypothesis that methionine supplementation may increase protein-derived cysteine and upregulate cysteine synthesis, thereby improving glutathione synthesis during the early treatment of edematous SAM. DESIGN: The cysteine flux, its de novo synthesis and release from protein breakdown, and erythrocyte glutathione synthesis rate were measured in 12 children with edematous SAM in the fed state by using stable isotope tracers at 3 clinical phases as follows: 3 ± 1 d (±SE) [clinical phase 1 (CP1)], 8 ± 1 d [clinical phase 2 (CP2)], and 14 ± 2 d (clinical phase 3) after admission. Subjects were randomly assigned to receive equimolar supplements (0.5 mmol ⋅ kg(-1) ⋅ d(-1)) of methionine or alanine (control) immediately after CP1. RESULTS: In the methionine compared with the alanine group, cysteine flux derived from protein breakdown was faster at CP2 than CP1 (P < 0.05), and the change in plasma cysteine concentration from CP1 to CP2 was greater (P < 0.05). However, there was no evidence of a difference in cysteine de novo synthesis and its total flux or erythrocyte glutathione synthesis rate and concentration between groups. CONCLUSIONS: Methionine supplementation increased cysteine flux from body protein but had no significant effect on glutathione synthesis rates. Although cysteine is made from methionine, increased dietary cysteine may be necessary to partially fulfill its demand in edematous SAM because glutathione synthesis rates and concentrations were less than previous values shown at full recovery. This study was registered at clinicaltrials.gov as NCT00473031.

Prenatal factors contribute to the emergence of kwashiorkor or marasmus in severe undernutrition: evidence for the predictive adaptation model.

BACKGROUND: Severe acute malnutrition in childhood manifests as oedematous (kwashiorkor, marasmic kwashiorkor) and non-oedematous (marasmus) syndromes with very different prognoses. Kwashiorkor differs from marasmus in the patterns of protein, amino acid and lipid metabolism when patients are acutely ill as well as after rehabilitation to ideal weight for height. Metabolic patterns among marasmic patients define them as metabolically thrifty, while kwashiorkor patients function as metabolically profligate. Such differences might underlie syndromic presentation and prognosis. However, no fundamental explanation exists for these differences in metabolism, nor clinical pictures, given similar exposures to undernutrition. We hypothesized that different developmental trajectories underlie these clinical-metabolic phenotypes: if so this would be strong evidence in support of predictive adaptation model of developmental plasticity. METHODOLOGY/PRINCIPAL FINDINGS: We reviewed the records of all children admitted with severe acute malnutrition to the Tropical Metabolism Research Unit Ward of the University Hospital of the West Indies, Kingston, Jamaica during 1962-1992. We used Wellcome criteria to establish the diagnoses of kwashiorkor (n = 391), marasmus (n = 383), and marasmic-kwashiorkor (n = 375). We recorded participants' birth weights, as determined from maternal recall at the time of admission. Those who developed kwashiorkor had 333 g (95% confidence interval 217 to 449, p<0.001) higher mean birthweight than those who developed marasmus. CONCLUSIONS/SIGNIFICANCE: These data are consistent with a model suggesting that plastic mechanisms operative in utero induce potential marasmics to develop with a metabolic physiology more able to adapt to postnatal undernutrition than those of higher birthweight. Given the different mortality risks of these different syndromes, this observation is supportive of the predictive adaptive response hypothesis and is the first empirical demonstration of the advantageous effects of such a response in humans. The study has implications for understanding pathways to obesity and its cardio-metabolic co-morbidities in poor countries and for famine intervention programs.

Nutritional repletion of children with severe acute malnutrition does not affect VLDL apolipoprotein B-100 synthesis rate.

VLDL apo B-100 is essential for the secretion of liver fat. It is thought that synthesis of this lipoprotein is impaired in childhood severe acute malnutrition (SAM), especially in the edematous syndromes, and that this contributes to the common occurrence of hepatic steatosis in this condition. However, to our knowledge, it has not been confirmed that VLDL apo B-100 synthesis is slower in edematous compared with nonedematous SAM and that it is impaired in the malnourished compared with the well-nourished state. Therefore, VLDL apo B-100 kinetics were measured in 2 groups of children with SAM (15 edematous and 7 nonedematous), aged 4-20 mo, at 3 stages during treatment. Measurements were done at 4 ± 1 d postadmission, mid- catch-up growth in weight, and at recovery (normal weight-for-length). VLDL apo B-100 synthesis was determined using stable isotope methodology to measure the rate of incorporation of (2)H(3)-leucine into its apoprotein moiety. The fractional and absolute synthesis of VLDL apo B-100 did not differ between the groups or from the initial malnourished stage to the recovery stage. Concentrations of VLDL apo B-100 were greater in the edematous than in the nonedematous group (P < 0.04) and did not differ from the initial stage to recovery. The data indicate that VLDL apo B-100 synthesis is not reduced when children develop either edematous or nonedematous SAM.

Lipid kinetic differences between children with kwashiorkor and those with marasmus.

BACKGROUND: It has been hypothesized that one factor associated with poor prognosis in kwashiorkor, but not in marasmus, is impaired lipid catabolism, which limits the supply of energy that is essential for survival when dietary intake is inadequate. However, this hypothesis has not been tested. OBJECTIVE: The objective was to measure lipid kinetics in malnourished children with kwashiorkor or marasmus. DESIGN: Glycerol concentration and flux (index of total lipolysis), palmitate concentration and flux (index of net lipolysis), and palmitate oxidation rate (index of fatty acid oxidation) were measured in 8 children (n = 5 boys and 3 girls) with kwashiorkor and 7 (n = 4 boys and 3 girls) with marasmus, aged 4-20 mo, in the postabsorptive state. The measurements were made approximately 3 d after admission, when the children were malnourished, and after the children attained normal weight-for-length, ie, at recovery. RESULTS: The glycerol concentration was higher in the malnourished stage than at recovery for the marasmus and kwashiorkor groups combined. Glycerol flux tended to be lower (P = 0.067) and palmitate flux significantly lower (P < 0.05) in the kwashiorkor group than in the marasmus group. Palmitate oxidation was significantly lower in the malnourished stage than at recovery in the kwashiorkor group but not in the marasmus group. In the malnourished stage, palmitate oxidation was slower in the kwashiorkor group than in the marasmus group, but no significant differences between groups were observed at recovery. CONCLUSIONS: Children with kwashiorkor break down fat and oxidize fatty acids less efficiently than do children with marasmus; this factor may explain the better survival rate in marasmus.

Polymorphisms in genes involved in folate metabolism as risk factors for oedematous severe childhood malnutrition: a hypothesis-generating study.

BACKGROUND: Severe childhood malnutrition (SCM) occurs as both oedematous and non-oedematous syndromes. The reasons why some children develop oedematous SCM (OSCM) have remained elusive but differences in clinical presentation among malnourished children from similar backgrounds suggests that there might be inter-individual variation in susceptibility to OSCM. AIM: To estimate the strength of the association between variants of three genes involved in folate/methyl group metabolism [methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and cystathionine beta-synthase (CBS)] and risk of OSCM. METHODS: Patients previously admitted to the Tropical Metabolism Research Unit (TMRU) for treatment of either OSCM (cases, n = 74) or non-oedematous SCM (NOSCM, controls, n = 50) were recruited. Genotypes at four sites within the three genes (MTHFR C677T, MTHFR A1298C, MTR A2756G and CBS 844ins68) were determined using PCR-based assays. RESULTS: The MTHFR 677T [odds ratio (OR) 0.63, 95% CI 0.2-1.7] and MTR 2756G (OR 0.74, 95% CI 0.4-1.4) alleles were associated with moderate reduction in risk of OSCM whereas the CBS 844ins68 allele (OR 1.4, 0.7-2.4) was associated with an increased risk. None of these risks was significant at the 5% level. CONCLUSIONS: Genetic variation within folate/methyl group metabolic pathways might have a small but potentially important influence on risk of OSCM. Additional, larger data-sets will be required to test the specific hypotheses (about the putative effect size and direction of association) generated in this preliminary study. Such observations have the potential to improve our understanding of the pathogenesis of clinical heterogeneity in severe malnutrition.

The effect of aromatic amino acid supplementation on a1- antirypsin synthesis in oedematous malnutrition

OBJECTIVES: We have previously demonstrated that infected children with oedematous protein energy malnutrition have an impaired acute phase response to infection. We hypothesize that this impaired response is due to a relative shortage of aromatic amino acids. We therefore sought to determine whether supplementation of the diet of infected oedematous malnourished children with aromatic amino acids (70 mg/kg/d phenylalanine, 80 mg/kg/d N-acetyltyrosine, 30 mg/kg/d tryptophan) would increase the rate of synthesis of acute phase proteins compared with an isonitrogenous diet supplemented with alanine. METHODS: In oedematous malnourished children, a primed continuous infusion of 3H2-leucine was used to determine the in vivo synthesis rates of a1-antirypsin (a1-at), an acute phase protein, when they were infected (Study 1) and after clearing of infection (Study 2). RESULTS: There was effect of aromatic amino acid supplementation on the rate of synthesis or concentration of a1-at. CONCLUSION: Supplementation of the diet of oedematous malnourished children with aromatic amino acids did not enhance the immune response as determined by the in vivo synthesis of a1-at. (AU)

Plasma volume in protein energy malnutrition

OBJECTIVES: This study compared two dye dilution techinques using Evans' blue (EB) for measurements of plasma volume (PV) in 21 children with protein energy malnutrition (PEM), (10 kwashiorkors, 6 marasmic kwashiorkors, 5 marasmics), 9-16 days post-admission when the children were malnourished and uninfected (study 1), and again on nutritional recovery (weight/height > 90 percent)(study 2). METHOD: A bolus of 2.5 mg of EB was infused and blood samples were obtained at 10,20,40 and 60 minutes post-infusion for the measurement of EB concentrations. Plasma volume was calculated using the arithmetic mean of the EB concentration at 10 and 20 min (EBM) and by the extrapolation to zero time of the log EB concentration vs time (10-60 min) curve (EBL). RESULTS: There was no difference in PV between the 3 clinical malnourished syndromes in studies 1 and 2 using either method. However, nutritional recovery was associated with a significant decrease in PV 72 ñ 12 to 65 ñ 9 ml/kg (mean ñ SD) by the EBL method (p < 0.009). Although there was significant concordance between the 2 methods (Lins p = 0.78, with 95 percent CI 0.67,0.89) the slope of 1.1 for the reduced major axis of EBM vs EBL and a bias correction factor of 0.88 suggested a systematic bias. The Bland-Altman analysis showed that PV values obtained by EBM were on average greater than PV values obtained by EBL (mean difference ñ SD, 5.4 ñ 5.2 ml/kg) and that the two methods will produced PV values that are consistently within ñ 10.2 ml/kg of each other. CONCLUSION: The two methods are not interchangeable for estimates of absolute PV. However, in a repeated measures design, the two methods are interchangeable as measures of malnutrition induced changes in PV.(Au)

Metabolic handling of different fatty acids during rehabilitation from childhood malnutrition

The gastrointestinal handling and post absorptive metabolism of [1, 1, 1-13 C] triolein (TO) and [1, 1, 13 C] tripalmitin (TP) were studied in two groups of eight severely malnourished children (5-0 months): on admission (Phase 1), during rapid-catch up growth (Phase 2) and when weight for height had reached 90 percent of the reference (Phase 3). Total excretion of 13 C label in stool (over 3 days) and breath as 13 CO 2 (over 24 hours) were analysed by isotope radio mass spectrometry. Stool 13 C excretion at admission was approximately 10 percent of the administered dose for both trials but varied markedly between subjects, was significantly reduced during rehabilitation in the TO trial (Phase 2:0.5 +or- 1.0; Phase 3: 1.3 +or- 0.9; p<0.05) and tended to decline on the P trial. ANOVA analysis of the magnitude and time course of 13 C excretion in breath (from area under the curve), excretion tended to decrease during rehabilitation in the TO trial but remained unchanged on the TP trial. These results suggest that the efficiency with which dietary triacylglycerol is handled within the gastrointestinal tract is generally impaired in severely malnourished children at admission but improves during rehabilitation.(Au)

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 percent. 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.(AU)

Albumin kinetics in edematous and nonedematous protein-energy malnourished children

The kinetic changes responsible for decreased plasma albumin and the relation between plasma albumin and the edema of protein-energy malnutrition (PEM) were investigated by measuring the plasma concentration, fractional (FSR) and intravascular absolute (ASR) synthesis rates of albumin in seven edematous and seven nonedematous children with PEM by using constant intragastric infusions of [2H3] leucine. Studies were done 2 d postadmission (study 1), 8 d postadmission (study 2), and at recovery (study 3). In study 1 there were no significant differences in plasma albumin concentrations in nonedematous and edematous children. In both groups, albumin concentrations but not FSRs were lower in studies 1 and 2 than in study 3. The ASR was lower only in edematous patients. These results suggest that repletion of the albumin pool of children with PEM is not mediated by changes in the FSR, and the edema of malnutrition is not solely due to hypoalbuminemia. (AU)

The effect of splenectomy for hypersplenism on whole body protein turnover, resting metabolic rate and growth in sickle cell disease

OBJECTIVE: To determine whether, in the same individual, an observed fall in whole body protein turnover following splenectomy in children with hypersplenism and homozygous sickle cell (SS) disease is associated with a measurable fall in resting metabolic rate (RMR) and an increase in rate of growth. SUBJECTS: Six children (5 SS disease, 1 S beta degree thalassaemia), aged 68 to 126 months, were studied before and after splenectomy for hypersplenism. DESIGN: Protein turnover was measured by the end product method using prime/intermittent oral doses of 15N-glycine and RMR by indirect calorimetry before preoperative transfusion and repeated at least eight weeks after splenectomy. Height and weight velocities were measured over six month periods before and after splenectomy. SETTING: University Hospital of the West Indies in Jamaica and the Medical Research Laboratories (Jamaica). RESULTS: After splenectomy protein turnover fell significantly by 30 percent and RMR by 34 kJ/kg/d. Mean weight velocity which was below normal before surgery, z = -2.3, improved significantly after surgery, z = 0.7, (p = 0.03). Height velocity increase in two children but the mean height velocity did not change following splenectomy. The reduction in protein turnover was estimated to account for 62 percent of the fall in RMR. CONCLUSION: This study confirms that there is a significant reduction in energy expenditure following splenectomy for hypersplenism in SS disease. A reduction in protein turnover was a major contributor to the saving in energy, although it is not clear whether it accounted for all. In the present group of children the energy saved was associated with an improvement in the wasting present before splenectomy.(AU)

Urea production and salvage during pregnancy in normal Jamaica women

The pattern of aggregated 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 [15N15N]-urea by dilution of label in urinary urea. Dietary protein intake was greater in trimester 1 than in nonpregnant women (167 ñ 36 vs 224 ñ 60 mg N.kg-1.d-1), and increased further in trimester 2 (266 ñ 59 mg N.kg-1.d-1). Urea production was not higher during pregnancy. Despite higher protein intake urea salvage was higer in pregnancy (40 ñ 24 nonpregnant vs 77 ñ 23, 61 ñ 31, and 51 ñ 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 (AU)

Urea kinetics in normal pregnancy - abstract

There is need for an increase in protein deposition during pregnancy. However, the requirement for dietary protein and also the pattern of the increased needs throughout gestation remains unclear. Based on nitrogen balance studies, a single value for the daily allowance throughout pregnancy has been proposed by various expert committees with recognition of the inherent limitations of this recommendation. Urea kinetics which represent a sensitive marker for the adequacy of dietary protein was measured in trimesters 1, 2, and 3 in 13 healthy pregnant women and in 8 healthy non-pregnant women (controls) using the prime/intermittent intravenous presentation of 15N 15N urea. The results are given in a Table. P/I indicates that although more protein was consumed in pregnancy compared to the controls, less was oxidised. Also E/I was significantly less at all stages of pregnancy. T, that portion of P that was salvaged and not excreted, was highest in the 1st trimester. It contributes to the nitrogen available for metabolism and is 20 - 30 per cent of P when protein intake is adequate. T+I, the total nitrogen available for metabolism was highest in the 2nd trimester. The results suggest that the demand for nitrogen is not constant throughout pregnancy and that there is an increased demand in early pregnancy. In particular, this increase was not met by the quantity and/or quality of the deitary intake in the first trimester. These changes in nitrogen metabolism have important implications for making recommendations for dietary protein intake during pregnancy (AU)

Excessive excretion of 5-oxoproline and decreased levels of blood glutathione in type II diabetes mellitus

Levels of blood glutathione (GSH) were measured in 26 type II diabetes mellitus patients compared to 36 controls. Total blood GSH did not differ significantly between the two groups (mean ñ s.d., 8.0 ñ 1.5 vs 7.7 ñ 1.3 mmol/g Hb, respectively); however reduced GSH was lowered in diabetes mellitus (5.0 ñ 1.0 vs. 5.8 ñ 1.0 mmol/gHb; P=0.01), whereas oxidized GSH was increased (0.4 ñ 0.2 vs. 0.2 ñ 0.1 mmol/gHb; P = 0.001). Urinary excretion of 5-oxoproline was excessive in the diabetic patients (14.5 ñ 9.9 vs. 3.8 ñ 1.4 mmol/24 h; P = 0.004), and was positively correlated with levels of glycosylated haemoglobin (r = 0.69; P < 0.01). (AU)

The effect of splenectomy on whole body protein turnover in homozygous sickle cell disease

In individuals with homozygous sickle cell (SS) disease, haemolysis creates a demand for increased red cell production. In children with hypersplenism haemolysis may be further increased and in such cases the excessive red cell production may be reduced by splenectomy (1). Whole body protein turnover is increased in SS disease and a large part of this increase is the consequence of increased turnover of red blood cells (2). Whole body protein turnover has therefore been measured in children with SS disease before and after splenectomy to find out if the reduction of the haemolytic rate following splenectomy was associated with a decrease in protein turnover. (AU)