Acute-phase protein response to infection in severe malnutrition

It is not known whether malnourished infant can mount a comprehensive acute-phase protein (APP) response and, if so, whether this is achieved by increasing APP synthesis rates. To address these issues, we measured 1) the plasma concentrations of five APPs (C-reactive protein, O1-acid glycoprotein, O1-antitrypsin, haptoglobin, and fibrinogen) and 2) the synthesis rates of three APPs (O1-antitrypsin, haptoglobin, and fibrinogen) using a constant intragastric infusion of [2H3] leucine in nine infected marasmic children at 2 days postadmission (study 1), 9 days postadmission when infections had cleared (study 2), and 59 days postadmission at recovery (study 3). Except for fibrinogen, the plasma concentrations of all APPs were higher in study 1 than in studies 2 and 3. Although the rate of synthesis of haptoglobin was significantly greater in study 1 than in study 2, the rates of fibrinogen and O1-antitrypsin synthesis were similar in all three studies. These results show that 1) severely malnourished children can mount an APP response to infection which does not include fibrinogen and 2) the APP response is accomplished through different mechanisms. (AU)

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 significantly inverse linear relationship overall for hydrolysis as a proportion of production and excretion as 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.(AU)

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-Loxoproline 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 increase 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 sythesis of non-essential amino acids, especially glycine.(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)

State of the art lecture: pharmacological intervention for the reduction of progression of diabetic nephropathy - abstract

Reduction of bloodpressure has been known, from the work of Parving et al (1987), to reduce the rate of decline of renal function in the nephropathy associated with Type-1 diabetes mellitus (IDDM), using conventional anti-hypertensive agents. More recently, interest in angiotensin-converting enzyme inhibitors (ACE-Is), and calcium channel blockers (CCBs) in the treatment of diabetic nephropathy, has been forthcoming. In diabetic nephropathy, induced in rats by streptozotocin, ACE-Is clearly alter renal haemodynamics and reduce proteinuria. Reduction of proteinuria is also seen in humans with diabetic nephropathy, and there is a suggestion of preservation of renal function, although no long-term studies have been published. Two studies are underway in non-hypertensive microalbuminuric subjects, but these have also not been published. The group of ACE-Is appears to have similar action in reducing proteinuria in diabetic nephropathy, but the same cannot be said for the CCBs. They differ in their action in reducing proteinuria, and dilitiazem may stand alone in reducing proteinuria in human diabetic nephropathy. Debate continues on the mechanism for reduction in proteinuria. Amelioration in systemic hypertension plays a role for all classes of antihypertensive drugs used, but the ACE-Is may alter glomerular permselectivity and thereby bring about reduction in proteinuria. Dietary reduction or protein intake may also play a protein preserving renal function as may reduction of lipids (AU)

The effect of the level of dietary protein, carbohydrate and fat on urea kinetics in young children during rapid catch-up weight gain

The kinetics of urea metabolism were measured in children recovering from severe malnutrition. For a period of up to 10 d they receive one of four diets which provided 711 kj (170 kcal)/kg per d. Two groups received a diet with a high protein:energy (P:E) ratio of 10.6 percent (HP), enriched with either fat (HP/F) or maize starch and sucrose HP/C). Two groups received a diet with a low P:E ratio of 8.8 percent (LP), enriched with either fat (LP/F) or maize starch and sucrose (LP/C). The rate of weight gain on the HP diets was significsntly greater than on the LP diets. There was no difference in urea production between any of the four diets: HP/F 1.23 (se 0.12), HP/C 1.37 (se 0.14), LP/F 1.64 (se 0.22) LP/C 1.15 (se 0.15) mmol nitrogen/kg per h. On the HP diets urea excretion was 0.77 (se0.07) mmol N/kg per h, 61 percent of production. There was significantly less urea excreted in the urine on diet LP/C than on LP/F (0.36 (se0.05) and 0.64 (se 0.04)mmol N/kg per h respectively). A significantly greater percentage of the urea production was hydrolysed on the LP diets (61 percent) compared with the HP diets (39 percent), with the consequence that 50 percent of urea-N produced was available for synthetic activity on the LP diets compared with 30 percent on the HP diets. The increase in the urea hydrolysed on the LP diets was equivalent in magnitude to the decreased intake of N, so that overall intake plus hydrolysis did not differ between the LP and HP diets. Crude N balance was similiar on diets HP/F, HP/C and LP/C, but was significantly reduced on diet LP/F. These results show that there is an accommodation in urea kinetics during rapid catch-up weight gain, which becomes evident when the P:E ratio of 8.8 percent, protein is limiting for catch-up growth. When the intake has a P:E ratio of 8.8 percent the pattern of urea kinetics can be modified by the relative proportion of fat and carbohydrate in the diet. The measurement of urea kinetics provides a useful approach to the definition of the adequacy of the protein in the diet. (AU)

Dietary intakes and activity levels of stunted and non-stunted children in Kingston, Jamaica. Part I. dietary intakes

The dietary intakes and activity levels of stunted and non-stunted children were measured on enrolment to a longitudinal study of growth and development. Children aged 9-24 months were recruited by house to house survey of several poor areas of Kingston. All children with height for age < -2 SD of the NCHS standards and weight for height below the standard median were enrolled. Alternate atunted children were matched for age and sex with the non-stunted child (height for age > -1 SD) living nearest. Dietary information was obtained by two 24-h recalls. Mean trainer-interviewer reliability was > 90 percent throughout the study. Correlation between energy intakes on the 2 days was 0.68 (P < 0.001). Stunted children had a significantly less varied diet, fewer dairy products and fruit than non-stunted children. Protein intakes met requirements. Energy intakes were similar in both groups and approximately 200 kcal below the recommended intake. Energy and protein intakes per kg were significantly higher in the stunted children than in non-stunted children (energy P < 0.001, protein P < 0.005). Greater morbidity in the stunted children could account for some, but not all, of this difference. Children with lower weight for height had lower intakes (energy P < 0.05, protein P < 0.01). Intakes were greater in children who lived in better housing, with more household possessions and whose mothers had more skilled occupations. Good reliability and the above associations indicate that the data are valid.(AU)

Changes in red cell insulin receptors during recovery from severe malnutrition

Red cell insulin binding was studied in 13 Jamaican children (age range 4-24 months), while malnourished (MAL), during early recovery (GI), late recovery (GII), and after anthropometric recovery (REC). The rate of weight gain (RW), the energy intake (EN), and the protein intake (PR) were monitored at each phase of the study. Four-hour fasting blood samples were used, and the insulin binding characteristics were investigated in the physiological range of insulin concentrations (16.7-1670 pM). Analyses of variance were used to examine differences in the variables measured at the four phases. Red cell-specific insulin binding (SB) was lower in MAL than in GI (P<0.001) and in (GII) (P=0.026). SB in REC and MAL were not significantly different. Insulin receptor affinity (K) was also lower in MAL than in GI (P<0.001), GII (P<0.001), and REC (P=0.012). The insulin receptor number (S) appeared to be high in malnutrition and to decrease as recovery progressed; however, the decrease was not significant. Children with fever demonstrated high insulin binding. Plasma insulin (IN) rose during recovery, and was significantly higher in GII than in MAL (P=0.01). There was no difference in plasma glucose (G) at any phase of the study. The interrelationships among the variables measured were investigated longitudinally using multiple regression analyses. SB was positively associated with S (P=0.032), EN (P=0.029), and PR (P=0.0076). S was negatively associated with K (P<0.001). The associations of S and K with PR were positive and approached significance (P = 0.09 and P = 0.07 respectively). RW was positively associated with PR (P<0.001), and with EN (P=0.001). There were no significant relationships between G and any of the other variables longitudinally. However, correlations of the variables within phases demonstrated that in MAL, G was negatively associated with SB (P<0.05) and with K (P<0.05); but in REC, G was positively associated with SB (P<0.05). These results demonstrated that in severe malnutrition, the red cell insulin receptor affinity was low. During catch-up growth when protein and energy intakes were increased, both insulin receptor affinity and specific insulin binding were also increased. The negative relationship between insulin binding and plasma glucose during malnutrition may be related to carbohydrate intolerance (AU)

Whole-body protein turnover in man determined in three hours with oral or intravenous 15N-glycine and enrichment in urinary ammonia

Studies were carried out in eight normal adults to simplify the continuous infusion-end product method for measuring whole-body protein turnover using 15 N-glycine. When a priming dose of label suitable for the urea pool was followed by intermittent oral doses of label, plateau enrichment was maintained in urinary urea and ammonia from 9 to 18 h, giving values for nitrogen flux. (18h) of 0.69ñ0.05 g N/kg/d with urea and 0.46ñ0.01 g N/kg/d with ammonia. With a priming dose appropriate for the ammonia pool, plateau was reached in urinary ammonia in less than 120 min an maintained for up to 6h. Nitrogen flux (3h) with oral 15N-glycine was 0.96ñ0.12 g N/kg/d, and with intravenous label was 0.61ñ0.13 g N/kg/d. There was a significant linear relationship between flux measured with oral and intravenous isotope. It is suggested that different components of protein turnover are measured with the different approaches, and that the short method in particular measures rapidly turning over proteins associated with the gastrointestinal tract.(AU)

Severe undernutrition in Jamaica - kwashiorkor and marasmus: the disease of the weanling

The syndromes of severe undernutrition, marasmus and kwashiorkor, have causes related to the interplay of social and medical considerations in the society. Kwashiorkor supervenes when the individual is exposed to a level of stress that exceeds the body's ability to cope. One final common pathway, through which a variety of environmental factors exert an effect, may be associated with oxidant damage to cells. In kwashiorkor there is a severe decrease in the level of both oxidised and reduced glutathione in the red cell. This could be caused by a decreased production, increased consumption or a combination of the two. This is discussed with specific reference to the metabolism of glycine and the possible causal relationship to the pathophysiology of the disease process.(AU)

Relationship between hepatic glutathione and fatty infiltration of the liver

One of the most serious complications of severe protein-energy malnutrition (PEM) is hepatic failure, which is usually associated with fatty infiltration of the liver. The precise biochemical cause of fatty liver is unknown. This study was designed to investigate the relationship between hepatic glutathione (GSH) and fat accumulation in the liver. Also, the experiment was designed in such a way as to determine the effects of different sources of dietary protein. Twenty-one days old weanling rats were fed for 20 days on diets containing adequate protein (Purina Laboratory Chow) (PLC) and Casein (CC - 23 percent protein), low protein (LP - 7 percent Casein), low protein supplemented with cysteine (LPC) to the level in the CC diet and, choline deficient diet (CD). The animals were weighed on the days of weaning and sacrifice. On the day of sacrifice, the blood, liver and kidney were rapidly removed, liver and kidney blotted on filter paper, weighed and GSH and fat measured using standard procedures. Animals on the CD diet lost weight and had twice the hepatic GSH levels compared to rats on the LP diet. However, they did not develop fatty livers as expected due to the deterioration of the diet in storage. Rats on the PLC diet had significantly gretaer body weight gains (p<0.01), higher liver GSH and cysteine values and lower liver triglyceride (TG) values than rats on the CC diet. Thus, the CC diet was used as the reference diet since the test diets were casein-based formulae. Rats on the LP diet showed reduced body weight gain and fat-free dry liver weight (FFDLW) values compared to the control. Liver glutathione (GSH) and cysteine concentrations were also reduced but there was no significant change in kidney and blood GSH concentrations. Liver fat and triglyceride (TG) values were significantly increased compared to the control (p<0.01). The addition of cysteine to the LP diet, dramatically increased liver GSH, FFDLW and body weight values and prevented liver fat and TG levels from increasing. It is concluded that the hepatic GSH and fat levels in weanling rats depend not only on the cysteine content of the diet but, also on the quality and composition of protein in the diet. Also, that cysteine directly or by maintaining liver GSH levels, prevented the increase of liver fat found in weanling rats on the LP diet (AU)

A supplementary feeding programme for the management of severe and moderate malnutrition outside hospital

Eighty-seven children with moderate and severe malnutrition were treated by means of a supplementary feeding programme in Trinidad. The programme resulted in an average weight increase similar to that obtained by other authors in Nutrition Rehabilitation Centres and Supervised Supplementary Feeding Programmes elsewhere, over a similar period of time. The weight increase, however, is slow when translated into improvement of reference weight for age. Close supervision resulted in a somewhat faster rate of improvement but increase excessively the cost of rehabilitation. Supervision and education of the mothers carried out by Community Aides did not result in continued improvement after discontinuation of the supplement. However, there was a significant improvement in the quality of the diet given to the supervised children four months after the food supplement and supervision had been discontinued. (Summary)

Whole-body protein turnover and nitrogen balance in young children at intakes of protein and energy in the region of maintenance

Nitrogen balance and whole-body protein turnover were measured in children aged about one year taking diets which provided 1.7 or 0.7 g milk protein/kg/d at three levels of metabolizable energy, 80, 90 and 100 kcal/kg/d. All the children were in positive nitrogen balance at all levels of energy intake on 1.7 g protein/ kg/d. Nitrogen equilibrium was maintained on 0.7 g protein/kg/d when the energy intake exceeded 90 kcal/kg/d, but on 80 kcal/kg/d nitrogen balance was negative. Whole-body protein turnover was measured from the enrichment in urinary ammonia following a continuous infusion of15N-glycine. The variation between individuals on the same diet was significantly greater than the variation within individuals at different levels of energy intake. For the group as a whole protein synthesis on 1.7 g protein/kg/d was 0.74, 0.75 and 0.87 g N/kg/d on 100, 90 and 80 kcal/kg/d respectively;whereas on 0.7 g protein/kg/d it was 0.37, 0.38 and 0.40 g N/kg/d. These results show that over this range of intakes protein synthesis decreased as dietary protein fell, but tended to increase as energy intake fell. (AU)

Protein deficiency, energy deficiency, and the oedema of malnutrition

The role of dietary protein deficiency in kwashiorkor is uncertain, although it has been shown not to be involved in the famine oedema of adults. A study of six different diets given to 103 children with oedematous malnutrition showed that the rate of loss of oedema was strongly correlated with the dietary energy intake (r=-0.75) but not with the protein intake (r=0.03). 66 patients given a very-low protein diet (2.5 percent protein energy) lost oedema as fast as those given five times as much protein. The energy intake above which oedema accumulated was 245-270 KJ/kg/day. Because energy deficiency is not invariably associated with oedema it cannot be the only factor involved, and the other necessary dietary component(s) must therefore have been present in surfeit in all the therapeutic diets. This could be potassium together with factors necessary for its retention. The accessory ingredients must be low in foods associated with human and experimental nutritional oedema. It is suggested that protein deficiency is not the cause of the oedema of kwashiorkor and that there is no need to postulate a different pathogenesis for this oedema from starvation oedema of adults. (Summary)

Body composition and hormonal studies during protein energy malnutrition and subsequent re-feeding on different diets

Weanling rats were used as experimental models to determine the changes in body composition, insulin output and rate of weight gain during P.E.M. and recovery from P.E.M. on different diets. The treatments were 1) ad libitum food intake to obtain "normal" growth, 2) restricted food intake to produce malnutrition, and 3) restricted food intake followed by any five experimental diets fed in ad libitum quantities. The malnourished rat model showed an increase in total body water percent, total body protein percent and decreased total body fat percent. Fasting plasma insulin levels were low and rate of weight gain was negligible. Recovery from P.E.M. occured in two stages: 1) an early spate of rapid growth associated with increased insulin output and increased synthesis of lean tissue and 2) a later spate of slow growth associated with decreased insulin output and increased deposition of fat tissue. Rapid recovery was achieved on only two of the diets. The rats which recovered on the diet which supported "normal" growth in control rats demonstrated "normal" body composition. "Abnormal" body composition was observed in rats recovering on a high protein, high energy diet which had a high percentage of fat. They had increased total body fat percent after recovery. Rats failed to recover on diets which were low in protein although adequate in energy. They demonstrated increased total body fat percent and decreased total body protein percent. Fasting plasma insulin levels and rates of weight gain were low. Rats failed to recover on a high energy, high protein diet which had a high percentage of sucrose. There was a high mortality on this diet. Total body protein percent was increased and low plasma insulin levels were obtained (AU)