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Antioxidant vitamins in malnourished Nigerian children.

The antioxidant capacity in malnutrition--as far as it is related to vitamins--was studied by determining the plasma concentrations of the most prominent antioxidant vitamins (retinol, tocopherols, carotenoids, cryptoxanthine, lycopene, and ubiquinone-10) in marasmic (M; n = 15), severe marasmic (SM; n = 8), kwashiorkor (KW; n = 12), and normally nourished (CO; n = 18) children in Nigeria. Retinol was found to be reduced in severe marasmic children when compared to local controls (medians and interquartile ranges; SM: 155 micrograms/l, 117-178 micrograms/l; CO: 281 micrograms/l 209-413 micrograms/l; p < 0.005). A strong correlation between plasma retinol and retinol binding protein could be found in all groups (SM: r = 0.79; M: r = 0.93; KW: r = 0.80; CO: r = 0.70). The tocopherol/lipid-ratio was lowered in kwashiorkor (median 0.48 mg/g, interquartile range 0.41-0.66 mg/g). A sufficient tocopherol status was only found in one child with kwashiorkor. alpha-Carotene, beta-carotene, cryptoxanthine and lycopene were below the detection limits in most of the malnourished children. Plasma ubiquinone-10 was significantly higher in kwashiorkor (median 1.05 micrograms/ml, interquartile range 0.88-1.17 micrograms/ml) than in all other groups (CO: 0.71 micrograms/ml, 0.55-0.99 micrograms/ml: M: 0.72 micrograms/ml, 0.65-0.83 micrograms/ml; SM: 0.89 micrograms/ml, 0.61-0.83 micrograms/ml). It is concluded that a depletion of antioxidant vitamins is present in malnourished Nigerian children, especially pronounced in the kwashiorkor syndrome. The mechanisms leading to elevated plasma ubiquinone-10 in kwashiorkor require further studies.

Antioxidants↗

Serum amino acids and genesis of protein energy malnutrition.

Twenty four patients of classical marasmus and kwashiorkor along with equal number of healthy controls were selected for the study. Their serum amino acid patterns analysis revealed a mean ratio of glutamate to alanine in fasting samples of normal individuals to be 0.33, while it as 9.3 in kwashiorkor and 1.6 in marasmus. This differences in controls, kwashiorkor and marasmus was statistically significant. This observation may explain evolution of marasmus and kwashiorkor in children with similar diets. On the basis of the present observation it is postulated that in kwashiorkor, the conversion of pyruvate to alanine in presence of glutamate, an aminogroup donor does not proceed normally, resulting in accumulation of glutamate and low alanine. Thus the development of marasmus and kwashiorkor may not be related to dietary inadequacy alone but also to the transaminase function. This could be genetic in origin.

Amino Acids↗

[3H]Ouabain binding to human erythrocytes in protein-énergy malnutrition.

[3H]Ouabain binding to erythrocytes was determined in normal children and in children suffering from kwashiorkor or marasmus. Scatchard plot analysis of [3H]ouabain binding displayed straight lines with linear slopes in all subjects indicating the presence of a single species of ouabain binding sites on erythrocytes. The number of ouabain binding sites per cell was 385 +/- 26 (mean +/- SEM, n = 3) in normal, 891 +/- 102 (n = 8) (p less than 0.001) in kwashiorkor and 316 +/- 45 (n = 3) in marasmic children. The equilibrium dissociation constant (Kd) for ouabain binding in kwashiorkor (16 nmol/1) was similar to that in control (12 nmol/1). The specific activity of Na+, K+ -ATPase of erythrocyte membrane has been shown to be higher in kwashiorkor children as compared to normal children [3]. This increase in enzyme activity may be considered as a consequence of increase in the enzyme content as indicated by the increased number of ouabain binding sites on red cells. Elevation in the level and activity of erythrocyte Na+, K+ -ATPase in kwashiorkor might represent a compensatory mechanism in response to a primary membrane abnormality, to effect prevention of Na+ accumulation and K+ depletion inside the cell.

Binding Sites↗

Glutathione and association antioxidant systems in protein energy malnutrition: results of a study in Nigeria.

Marasmus and kwashiorkor are manifestations of protein energy malnutrition. The pathophysiology of these disorders is poorly understood. We studied a number of blood antioxidants [glucose-6-phosphate dehydrogenase (G6PDH), glutathione reductase (GR) and its cofactor flavin adenine dinucleotide (FAD), the tripeptide glutathione as the major nonprotein thiol], serum albumin, and retinol-binding protein in 12 children suffering from kwashiorkor with all classical symptoms, in 13 patients with clinically severe marasmus, in 19 marasmic but active children, and in 23 controls. Significant changes were observed for erythrocyte glutathione and correspondingly for nonprotein thiols in whole blood (0.72 +/- 0.29 mM thiols in controls, 0.50 +/- 0.22 mM in marasmus, 0.35 +/- 0.23 mM in severe marasmus, and 0.22 +/- 0.13 mM in kwashiorkor). These differences were paralleled by a decrease in serum albumin concentration so that the molar ratio of nonprotein thiols/albumin had an average value of approximately 1.5 in all groups. The erythrocyte glutathione-reducing system, represented by G6PDH and glutathione reductase, showed only slight differences among the four groups of children; the supposition that kwashiorkor occurs predominantly in children with aberrant G6PDH could not be substantiated. Unexpectedly, erythrocyte FAD, an index of riboflavin status, was normal in most malnourished patients. Discussed is the prospect of administering glutathione in kwashiorkor patients.

Blood Proteins↗

Brainstem auditory and visual evoked potentials in children with protein-energy malnutrition.

BACKGROUND: To determine the effects of malnutrition on the developing brain with brainstem auditory evoked potentials (BAEP) and flash visual evoked potentials (fVEP). METHODS: The BAEP and fVEP of 11 kwashiorkor (8 +/- 1.56 months) and 10 marasmus (7.9 +/- 1.27 months) patients and 10 healthy control subjects (7.65 +/- 0.82 months) were recorded and the measurements were compared with each other in relation with plasma total protein and albumin levels. RESULTS: There were no differences between the mean latencies of the waves I, II, III and IV and mean interpeak latencies (IPL) of the waves I-III of the BAEP and the wave IV (N2) of the fVEP between the three groups. Mean latency of the wave V and mean IPL of the waves I-V and the waves III-V were significantly different between the three groups. The kwashiorkor group had significantly longer mean latency of the wave V than the marasmus group on the right ear and the control group on the both of the ears. The kwashiorkor group had significantly longer mean IPL of the waves I-V than the marasmus group on the right ear and than the control group on the left ear. The kwashiorkor group had also significantly longer mean IPL of the waves III-V than the control group on the left. CONCLUSIONS: The BAEP and fVEP are non-invasive electrophysiologic methods reflecting the integrity or disruption of the central neurologic pathways. The present results confirm the disruption of the central nervous system with the BAEP in children with protein-energy malnutrition, especially in kwashiorkor patients.

Analysis of Variance↗

Bacteraemia in severely malnourished children.

During a 2-year period, 792 severely malnourished children (kwashiorkor, marasmus and marasmic kwashiorkor) were hospitalized (14.8% of all admissions). Community-acquired bacteraemia was recorded in 7.7% and nosocomial bacteraemia in 2.2% of malnourished children. The relative risk for bacteraemia on admission was 1.6 (95% confidence interval [CI] 1.3-1.9) and 2.0 for nosocomial bacteraemia (95% CI 1.4-3.0) in malnourished children as compared with well nourished children. Bacteraemia was 3.5 times more common in children with kwashiorkor than in marasmic children. Gram-negative enteric aerobes were isolated 2.6 times more frequently from malnourished than from well nourished children. The relative risk of death in malnourished children with bacteraemia was 2.5 times that of malnourished children without bacteraemia. Thirty-six per cent of deaths in children with kwashiorkor were related to bacteraemia. This study emphasizes the increased risk of bacteraemia in malnourished children, particularly those with kwashiorkor, and the impact on mortality.

Bacteremia↗

Pro-inflammatory cytokines in Turkish children with protein-energy malnutrition.

BACKGROUND: Protein-energy malnutrition (PEM) results from food insufficiency as well as from poor social and economic conditions. Development of PEM is due to insufficient nutrition. Children with PEM lose their resistance to infections because of a disordered immune system. It has been reported that the changes occurring in mediators referred to as cytokines in the immune system may be indicators of the disorders associated with PEM. AIMS: To determine the concentrations of pro-inflammatory cytokines in children with PEM, and to find out whether there was an association with the clinical presentation of PEM. METHODS: The levels of serum total protein, albumin, tumour necrosis factor-alpha, and interleukin-6 were measured in 25 patients with PEM and in 18 healthy children as a control group. PEM was divided into two groups as kwashiorkor and marasmus. The kwashiorkor group consisted of 15 children and the marasmus group consisted of 10 children. RESULTS: Levels of serum total protein and albumin of the kwashiorkor group were significantly lower than both the marasmus group and controls (p < 0.05). In view of tumour necrosis factor-alpha levels, there was no difference between groups (p > 0.05). While levels of interleukin-6 in both the marasmus group and the kwashiorkor group were significantly higher compared with controls (p < 0.05), there was no significant difference between the groups of marasmus and kwashiorkor (p > 0.05). CONCLUSIONS: It was observed that the inflammatory response had increased in children with malnutrition.

Blood Proteins↗

Studies on hepatic and extrahepatic lipoprotein lipases in protein-calorie malnutrition.

Postheparin serum lipolytic activities (hepatic and extrahepatic), serum free fatty acid, and triglyceride levels were measured in 16 kwashiorkor, 14 marasmic, and 14 control children. The results showed that the reduction in total postheparin lipolytic activity in kwashiorkor was in the activity of hepatic origin. In marasmus, the total postheparin lipolytic activity, hepatic and extrahepatic activities, were within normal range. The was no evidence for the presence of inhibitors of postheparin lipolytic activity in the serum of kwashiorkor or marasmic children. Fasting serum-free fatty acid level was significantly elevated in kwashiorkor, while the level in marasmus was not significantly different from control value. The serum triglyceride levels in both conditions showed no significant differences from the control value. These findings suggest that the defective production of hepatic lipoprotein lipase, as well as increased influx of free fatty acid into the liver, could account for the accumulation of fat in the liver of kwashiorkor and not in that of marasmic children.

Child, Preschool↗

Plasma thyroxine binding prealbumin as an index of mild protein-energy malnutrition in Nigerian children.

Weight, height, midarm circumference (AC), midarm muscle circumference (AMC), triceps skinfold thickness (TSF), and plasma thyroxine binding (TBPA) were measured in 73 children free from any clinical evidence of disease and in 15 severe protein-energy malnourished (PEM) (marasmus, marasmic kwashiorkor, and kwashiorkor) Nigerian preschool children. The children were divided into various groups according to both Wellcome and Waterlow's classification. All measurements made on them were then compared between the various groups within each classification. It was found that plasma TBPA values were not only able to distinguish various grades of PEM but was the only parameter studied which can distinguish mild PEM from normals when weight, height, TSF, AC, and AMC were not sensitive enough to do so. TBPA was also found to be significantly related to body weight, deficit in weight for age, AC, and AMC. Both marasmic and kwashiorkor groups had significantly lower TBPA levels than undernourished group. The marasmic children also had significantly lower body weight but higher TBPA levels than kwashiorkor, while the TBPA values for marasmic kwashiorkor children were in between the two. Considerable overlapping of individual TBPA values were found between normals and undernourished in Wellcome classification but very little overlapping was found between normals and mild PEM in Waterlow's classification.

Anthropometry↗

Inflammatory mediators in children with protein-energy malnutrition.

Edema is a typical sign in kwashiorkor, which is present in a subset of patients with protein-energy-malnutrition (PEM). The pathophysiology of this edema is not well established. One of the abnormalities found in kwashiorkor is reduced concentrations of antioxidants, suggesting a compromised capacity to neutralize free radicals, which are known to induce tissue damage. We have studied plasma concentrations of several mediators of the inflammatory cascade. Concentrations of interleukin 6 (IL-6), C-reactive protein, and the soluble receptors of tumor necrosis factor alpha (sTNFR-p55 and sTNFR-p75) are greater in children with PEM, particularly in those with kwashiorkor, whereas soluble receptors of IL-6 (sIL6R-gp80) and IL-1 receptor antagonist concentrations are not significantly different from those of healthy children. In addition, concentrations of IL-6, sTNFR-p55, and sTNFR-p75 are greater in kwashiorkor patients irrespective of the presence of infection. Antioxidant status, as determined by plasma concentrations of glutathione and vitamin E, is significantly reduced in kwashiorkor patients. These data support the notion that children with edematous malnutrition show increased inflammatory reactivity that may contribute to edema formation.

Antioxidants↗

Endocrine profiles in pediatric andrology. I. Thyroid-stimulating hormone response to thyrotropin-releasing hormone in normal and protein-calorie malnourished infants.

Thryotropin-releasing hormone (TRH) was intravenously administered to eight normal control infants and ten infants with kwashiorkor. Stimulation caused by TRH was measured at various time intervals. The basal total protein mean value +/- SE was 6.9 +/- 0.3 and 4.0 +/- 0.3 g/dl for the control and kwashiorkor groups, respectively. Serum total thyroxine was 7.7 +/- 0.6 and 4.8 +/- 0.8 micrograms/dl for the control and kwashiorkor groups, respectively. Serum levels of thyroid-stimulating hormone (TSH) were 3.2, 13.5, 9.0, 7.4, and 8.0 microU/ml for the controls before stimulation and 20, 60, 90, and 120 min after stimulation, respectively. The corresponding values for the infants with kwashiorkor were 5.7, 13.9, 14.9, 15.2, and 15.3 microU/ml, respectively. The delayed TSH response to TRH stimulation in the infants with kwashiorkor was attributed to disturbance in the hypothalamic-pituitary-thyroid axis.

Female↗

Clinical significance of serum transcobalamins in protein-energy malnutrition.

The serum concentrations of Unsaturated Vitamin B(12) binding (UBBC) capacity and the three individual transcobalamins were measured in 34 malnourished children aged 9 months-5 y. Levels of serum vitamin B12, aspartate aminotransferase, alanine aminotransferase, albumin and total proteins were also estimated. The serum UBBC, Transcobalamin I (TC I), Transcobalamin III (TC III), vitamin B12 and the enzyme activities were significantly higher in the kwashiorkor children when compared with both the marasmic and control children. There was also a marked reduction of serum Transcobalamin II (TC II), albumin and total proteins in the kwashiorkor children. In contrast with kwashiorkor, there was a slight increase of serum TC II in the marasmic children. Their serum UBBC, TC I, TC III and B12 were also raised but not as high as in kwashiorkor. These results are discussed in the light of the hepatic dysfunction in kwashiorkor affecting the production of TC II in the liver, while the elevated serum B12 in Protein-energy malnutrition (PEM) may be due to both hepatic damage and intensified release of TC I as a result of infection.

Journal Article↗

Growth hormone-binding proteins and insulin-like growth factor-binding proteins in protein-energy malnutrition, before and after nutritional rehabilitation.

To clarify the influence of nutrition on the GH-IGF axis in protein-energy malnutrition (PEM), we determined the serum levels of GH, GH-binding proteins (BP) (GHBPs), IGF-I, and IGFBPs in nine children with kwashiorkor and 13 with marasmus, before and after nutritional rehabilitation. In a basal condition, the GH level was significantly higher in the two malnourished groups than in controls (p < 0.01); in contrast, the second fraction of GHBP was lower and seemed to be related to the high GH and to a reduction in GH receptors. After refeeding, the GH level increased and the second fraction of GHBP decreased. The IGF-I basal level was higher in kwashiorkor than in marasmus subjects (p < 0.05), but in both groups it was significantly lower than in controls (p < 0.01); after refeeding it increased. IG-FBP-3, measured by RIA and Western blotting techniques, was in the control range in the kwashiorkor group but in the marasmic group it was significantly lower than in controls; after refeeding it decreased in kwashiorkor (p < 0.01 versus basal values) and increased in marasmus (p < 0.05 versus prerefeeding level). When sera of malnourished patients were mixed with adult control sera, incubated for 5 h at 37 degrees C, and assessed by ligand blotting, a low IGFBP-3 level in marasmus was found to be due to increased adaptive proteolysis of IGFBP-3; in contrast, in kwashiorkor the IGFBP-3 proteolytic activity was very low, probably because of inhibition by aflatoxins. These findings confirm that malnutrition affects the GH-IGF axis.

Adult↗

Clinical features of severe malnutrition at the pediatric ward of Dr. Pirngadi Hospital Medan.

A retrospective study on severe malnutrition concerning children hospitalized at the Pediatric ward of Dr. Pirngadi Hospital, Medan from January 1 to December 31, 1988 was conducted. Patients less than five years old were included in this study. The purpose of this study was to know the incidence of severe malnutrition, its symptoms and signs, the immunization status, feeding pattern and socio-economic factors. Out of the 3370 hospitalized patients, 2453 (72.78%) were children under five years old. Of these, 312 (12%) suffered from severe malnutrition. It consisted of marasmus 131 (41.9%), marasmic kwashiorkor 94 (30.1%) and kwashiorkor 87 (27.8%). The highest incidence was found in the age group of 0-2 years (58%). Clinical manifestation of marasmus were old man face (131 or 100%), muscular hypotrophy (118 or 71.9%) and decreased subcutaneous fat (116 or 71.1%) in marasmic kwashiorkor children 46 or 50% had their hair easily picked out, 45 or 46.3% showed hyperpigmentation and 48 or 52% had pretibial edema in the kwashiorkor group 29 or 63% had moon face, 52 or 60.4% showed crazy pavement dermatosis, 77 or 51.3% had hepatomegaly and 87 or 48% pretebial edema. Moon face was seen in 29 (63%), crazy Pavement Dermatosis in 52 (60.4%), hepatomegaly in 77 (51.3%), and pretebial edema in 87 (48%) of kwashiorkor cases. The accompanying diseases were mostly diarrhea (95%) and bronchopneumonia (22%). Immunization status showed that BCG comprised 50.6%, while DPT III and OPV III in 13.7% and 10.5% respectively and measles only 0.64%. More than half (59.6%) of them were breast-fed up to 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗

Vitamin E status in Sudanese children with protein-energy malnutrition.

Total tocopherols and alpha-tocopherols were estimated in the plasma of children with severe malnutrition (14 marasmus; 11 marasmic kwashiorkor; five kwashiorkor) and related to the total plasma lipids and different plasma lipid classes. If the mere plasma concentrations were taken as an index of the vitamin E status, five children with marasmus, five children with marasmic kwashiorkor, and two children with kwashiorkor would have been regarded as deficient (less than 500 micrograms/dl). However, if total tocopherols and alpha-tocopherols were related to the total plasma lipids, all malnourished children--except one--showed values within the limits found in healthy American children. The study shows that low tocopherol/lipid ratios are not a constant feature in severely malnourished children.

Child, Preschool↗

Classification of malnutrition by statistical analysis of quantitative two-dimensional gel electrophoresis of plasma proteins.

An attempt to use the relative concentrations of major plasma proteins for clinical assessment of severe malnutrition is described. Quantitative two-dimensional gel electrophoresis was used to measure the concentrations of 24 major proteins in small aliquots of plasma obtained from children, aged 0 to 3 years, who were patients and outpatients in Liberian hospitals. Fifteen had a clinical diagnosis of kwashiorkor, 36 were diagnosed with marasmus, and 18 were controls. There were also 5 controls from the United States. The individuals were placed in six groups; kwashiorkor, kwashiorkor who died during treatment, marasmus, marasmus who died, Liberian controls, and U.S. controls. The amount of protein in each spot in the two-dimensional gels was estimated by measuring bound stain using a laser scanner and computerized image analysis. We found very low serum transferrin levels in malnourishment, in agreement with reports from other investigators. All of the data for 24 protein variables were pooled for factor analysis; the mean factor scores for each group differed, with the kwashiorkor groups furthest from the controls. Results of discriminant analysis using the amounts of different numbers of protein variables (3 to 24) were compared for posterior assignment of individuals to groups. The validity of the method was tested by analysis of plasma aliquots obtained from patients following initiation of therapy and which were not a part of the training set. Predictive performance (prognosis of patient survival) depended upon the number of protein variables used. Although artifactual fitting of the data is expected to contribute to performance as the number of variables is increased, use of as many as 7 variables may be justified, even with our small patient groups. Possible use of these results for development of a practical clinical test is discussed.

Blood Protein Electrophoresis↗

Influence of nutritional status on child mortality in rural Zaire.

Although the association between nutritional status and mortality risk is obvious for extreme malnutrition, the issue is not so clear for mild to moderate undernutrition. We have investigated this association in children of 0-5 years in the rural area of Bwamanda, Zaire, where an integrated development project, with good medical facilities, has operated for 20 years. A random cluster sample of 5167 children was taken; newborn infants and immigrants were included at six quarterly survey rounds from October, 1989, until February, 1991. All surveys included clinical and anthropometric assessment of nutritional status. Deaths were recorded up to April, 1992; there were 246 deaths. Marasmus, kwashiorkor, and other causes of death were defined by the verbal autopsy method and checked against medical records kept at the central hospital and the peripheral dispensaries. As expected, we found an increased risk of death in severe malnutrition. When deaths directly attributed to marasmus or kwashiorkor were excluded, mild to moderate stunting or wasting were not associated with higher mortality in the short term (within 3 months of the previous study round) or in the long term (from 3-30 months after study entry). The commonest causes of death were malaria and anaemia. Extreme marasmus and kwashiorkor caused 16% of deaths, and are important causes of death even in this favoured area with an integrated development project. Nutritional interventions should be targeted more selectively so that children with moderate malnutrition can be protected from progression to marasmus or kwashiorkor.

Anemia↗

Circulating gonadotropin profile in severe cases of protein calorie malnutrition.

The circulating levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL) were studied in children of both sexes between 2 and 14 years of age who were suffering from severe protein calorie malnutrition (PCM), namely, kwashiorkor, marasmic kwashiorkor, and marasmus. LH and FSH levels in all the age groups and in all forms of PCM were found to be significantly lowered, thereby explaining the possible delay in the onset of puberty in these children. Circulating PRL levels, on the other hand, were significantly raised in all patients with PCM studied, with values in children with kwashiorkor and marasmic kwashiorkor higher than in children with marasmus, possibly accounting for the presence of edema in the former cases. The present work, therefore, proposes a possible correlation between gonadotropin levels and PCM in children.

Adolescent↗