Effects of induced-kwashiorkor on salivary parameters in Wistar rats.

BACKGROUND: This study was undertaken to determine changes induced by protein malnutrition (kwashiorkor). in the secretory functions of salivary glands and biochemical parameters of salivary fluid using rats. METHODS: Eighteen male Wistar rats were randomly divided into two groups (control and kwarshiorkor) of 9 rats each. The rats were fed with normal diet and low protein diet (2% protein) respectively for a period of 6 weeks. Stimulated saliva samples using pilocarpine (10 mg/kg body weight i.p.) were collected and salivary glands (parotid and submandibular) were surgically removed. Biochemical analysis of salivary secretion using salivary lag time, flow rate, pH, total protein and concentrations of electrolytes (Na+, K+, Ca++, Cl-, HCO(2-)3 PO4) were conducted and compared. Morphological assessment of the salivary glands was done using heamatoxyline-eosin and Alcian blue stains. RESULTS: Body weights decreased in the kwashiorkor group. Weights of submandibular and parotid glands (right and left) were lower in the kwashiorkor group compared to the normal diet group. The mean salivary lag time was increased while the salivary flow rate was reduced in the kwashiorkor group compared to normal diet group. Salivary electrolytes and total protein analysis showed reduced concentration of sodium while potassium and bicarbonate concentrations were increased in the kwashiorkor group compared to the normal diet group. Histological analysis of the H-E and alcian blue stained salivary glands in the kwashiorkor group exhibited moderate to severe acinar cell atrophy, periductal fibrosis and reduced mucin content. CONCLUSION: These findings suggest the role of functional and biochemical changes in salivary secretion in the pathophysiology of oral diseases associated with protein malnutrition.

A non-inflammatory form of immune competence prevails in acute pre-pubescent malnutrition: new evidence based on critical mRNA transcripts in the mouse.

The declining inflammatory immune competence of acute (i.e. wasting) pre-pubescent protein-energy malnutrition has been regarded as reflecting an unregulated immunological disintegration. Recent evidence, however, suggests that malnutrition stimulates a regulated immunological reconfiguration to achieve a non-inflammatory form of competence, perhaps offering protection against autoimmune reactions - the 'Tolerance Model'. Our objective was to determine the influence of acute pre-pubescent malnutrition on the expression of genes critical to tolerogenic regulation. Male and female C57BL/6J mice, initially 19 d old, consumed a complete purified diet either ad libitum (age-matched controls) or in restricted daily quantities (mimicking marasmus), or consumed an isoenergetic low-protein diet ad libitum (mimicking incipient kwashiorkor) for 14 d (six animals per dietary group). Gene expression in the spleen, typically an inflammatory organ, and in the small intestine, a site designed for non-inflammatory defence, was assessed by real-time quantitative RT-PCR, and normalised to ß-actin. In the spleen of the malnourished groups, both IL-10 and transforming growth factor-ß1 mRNA expression increased compared with controls (P < 0.05), whereas mRNA expression of IL-12p40 decreased (P < 0.05). Conversely, malnutrition exerted no influence on the expression of mRNA for these cytokines in the small intestine (P>0.05). Moreover, forkhead box P3 mRNA expression, indicative of cell-based tolerogenic potential, was sustained in both the spleen and intestine of the malnourished groups (P>0.05). Thus, despite limited supplies of energy and substrates, the spleen shifted towards a non-inflammatory character and the intestine was sustained in this mode in advanced pre-pubescent weight loss. These findings provide the first support for the Tolerance Model at the level of mRNA transcript expression.

Under-five protein energy malnutrition admitted at the University of Nigeria Teaching Hospital, Enugu: a 10 year retrospective review.

OBJECTIVE: To determine the prevalence, risk factors, co-morbidities and case fatality rates of Protein Energy Malnutrition (PEM) admissions at the paediatric ward of the University of Nigeria Teaching Hospital Enugu, South-east Nigeria over a 10 year period. DESIGN: A retrospective study using case Notes, admission and mortality registers retrieved from the Hospital's Medical Records Department. SUBJECTS: All children aged 0 to 59 months admitted into the hospital on account of PEM between 1996 and 2005. RESULTS: A total of 212 children with PEM were admitted during the period under review comprising of 127 (59.9%) males and 85 (40.1%) females. The most common age groups with PEM were 6 to 12 months (55.7%) and 13 to 24 months (36.8%). Marasmus (34.9%) was the most common form of PEM noted in this review. Diarrhea and malaria were the most common associated co-morbidities. Majority (64.9%) of the patients were from the lower socio-economic class. The overall case fatality rate was 40.1% which was slightly higher among males (50.9%). Mortality in those with marasmic-kwashiokor and in the unclassified group was 53.3% and 54.5% respectively. CONCLUSION: Most of the admissions and case fatality were noted in those aged 6 to 24 months which coincides with the weaning period. Marasmic-kwashiokor is associated with higher case fatality rate than other forms of PEM. We suggest strengthening of the infant feeding practices by promoting exclusive breastfeeding for the first six months of life, followed by appropriate weaning with continued breast feeding. Under-five children should be screened for PEM at the community level for early diagnosis and prompt management as a way of reducing the high mortality associated with admitted severe cases.

The effect of serum magnesium levels and serum endothelin-1 levels on bone mineral density in protein energy malnutrition.

An inadequate and imbalanced intake of protein and energy results in protein-energy malnutrition (PEM). It is known that bone mineral density and serum magnesium levels are low in malnourished children. However, the roles of serum magnesium and endothelin-1 (ET-1) levels in the pathophysiology of bone mineralization are obscure. Thus, the relationships between serum magnesium and ET-1 levels and the changes in bone mineral density were investigated in this study. There was a total of 32 subjects, 25 of them had PEM and seven were controls. While mean serum ET-1 levels of the children with kwashiorkor and marasmus showed no statistically significant difference, mean serum ET-1 levels of both groups were significantly higher than that of the control group. Serum magnesium levels were lower than normal value in 9 (36%) of 25 malnourished children. Malnourished children included in this study were divided into two subgroups according to their serum magnesium levels. While mean serum ET-1 levels in the group with low magnesium levels were significantly higher than that of the group with normal magnesium levels (p < 0.05), mean bone mineral density and bone mineral content levels were significantly lower (p < 0.05). In conclusion, many factors play a role in the pathophysiology of changes in bone mineral density in malnutrition. Our study suggested that lower magnesium levels and higher ET-1 levels might be important factors in changes of bone mineral density in malnutrition. We recommend that the malnourished patients, especially with hypomagnesaemia, should be treated with magnesium early.

Cranial magnetic resonance imaging findings in kwashiorkor.

Protein energy malnutrition (PEM) is an important public health problem in the developing countries, although it is becoming uncommon in South West Nigeria. Cerebral changes have been associated with severe PEM. This study evaluated the neurological changes using Magnetic Resonance Imaging (MRI) in Ibadan south west Nigeria. The 5 children evaluated had a median age of 16 months and all the children had brain changes compatible with cerebral atrophy. In addition two of the children had periventricular white matter changes, while one these two had mega cisterna magna in addition. Though this study did not re-evaluate the brains of these children after nutritional rehabilitation, it is possible that changes are reversible as demonstrated in earlier studies.

INCAP studies of kwashiorkor and marasmus.

This article summarizes thirty years of intensive clinical metabolic and therapeutic studies of the consequences of severe protein deficiency relative to calories, which results in kwashiorkor, and of a balanced deficiency of protein and calories that results in marasmus. Evidence is provided that these are two different metabolic diseases, but kwashiorkor is usually superimposed on some degree of chronic marasmus and hence most cases studied were marasmic kwashiorkor. The value of the creatinine/height index to indicate the degree of lean body cell mass with any disease is demonstrated.

Oedematous malnutrition.

Oedematous malnutrition, represented by its most severe form kwashiorkor, is rampant in many parts of the world and is associated with a high case fatality rate. Despite being first described more than a century ago, the pathogenesis of kwashiorkor is still not clear. The traditional thinking is that it results from a deficiency of dietary protein and is usually associated with an infection. This has now been challenged by the finding that there is no difference in diets of children developing marasmus or kwashiorkor. Nutritional oedema is associated with an increased secretion of anti-diuretic substance (probably antidiuretic hormone) which prevents the normal excretory response to water administration. Experimental studies have shown that feeding low-protein, low-calorie diets results in delayed and incomplete response to a water load, and that the livers of the animals show a reduced capacity for inactivating anti-diuretic hormone. There is now evidence that links generation of free radicals and depletion of anti-oxidants with the development of oedema in kwashiorkor.

Switching to normal diet reverses kwashiorkor-induced salivary impairments via increased nitric oxide level and expression of aquaporin 5 in the submandibular glands of male Wistar rats.

Kwashiorkor, a form of malnutrition, has been shown to cause impaired salivary secretion. However, there is dearth of information on the mechanism that underlies this complication. Also, whether returning to normal diet after kwashiorkor will reverse these complications or not is yet to be discerned. Thus, this study aimed at assessing the mechanisms that underlie kwashiorkor-induced salivary impairments and to evaluate the effects of switching back to normal-diet on kwashiorkor-induced salivary impairments. Weaning rats were randomly divided into 3 groups (control group, kwashiorkor group (KG), re-fed kwashiorkor group (RKG)) of 7 rats each. The control group had standard rat chow while the KG and RKG were fed 2% protein diet for 6 weeks to induce kwashiorkor. The RKG had their diet changed to standard rat-chow for another 6 weeks. Blood and stimulated saliva samples were collected for the analysis of total protein, electrolytes, amylase, immunoglobulin A (IgA) secretion rate, leptin, and ghrelin. Tissue total protein, nitric oxide level, expressions of Na+/K+-ATPase, muscarinic (M3) receptor, and aquaporin 5 in the submandibular glands were also determined. Data were presented as means ± SEM and compared using ANOVA with Tukey's post hoc test. RKG showed improved salivary function evidenced by reduced salivary lag-time and potassium and increased flow rate, sodium, amylase, IgA secretion rate, leptin, submandibular nitric oxide level, and aquaporin 5 expression compared with KG. This study for the first time demonstrated that kwashiorkor caused significant reduction in salivary secretion through reduction of nitric oxide level and aquaporin 5 expression in submandibular salivary glands. Normal-diet re-feeding after kwashiorkor returned salivary secretion to normal.

Decreased metabolism of 13C-caffeine via hepatic CYP1A2 in marasmus and kwashiorkor based on breath test.

BACKGROUND: Hepatic metabolism of drugs has been rarely studied in children with malnutrition. Caffeine breath test (CBT) has been used to determine the activity of cytochrome P450 1A2 (CYP1A2) enzymes in children. We used the CBT to assess how marasmus and kwashiorkor differentially affect 13C-caffeine metabolism. METHODS: A total of 45 children composed of 15 children per group of malnutrition (marasmus, marasmic-kwashiorkor, and kwashiorkor) were studied during malnutrition and after nutritional recovery. After an overnight fast, patients ingested 3 mg/kg 13C-caffeine at 0900 h. Duplicate breath samples were collected into an Exetainer bottle at -20, -10, and -1 min and at 15-min intervals for 2 h. The mean cumulative percent dose recovered (CPDR) of 13C-caffeine in the expired 13CO2 was determined over the study period. RESULTS: The CPDR in the expired 13CO2 in 2 h significantly increased after nutritional recovery in children with marasmus (from 6.80%±3.00% to 7.67%±2.81%; Student's t-test, p=0.001), marasmic-kwashiorkor (from 6.61%±2.26% to 7.56%±2.46%, p=0.041), and kwashiorkor (from 6.29%±1.06% to 7.20%±1.80%, p=0.002). When the three groups of malnutrition were compared, there was no significant difference in their mean CPDR in 2 h during malnutrition [p=0.820, analysis of variance (ANOVA)] and after nutritional recovery (p=0.810, ANOVA). CONCLUSIONS: Hepatic metabolism of caffeine significantly decreased in children with marasmus, marasmic-kwashiorkor, and kwashiorkor compared to after they had recovered nutritionally. This suggests a decreased CYP1A2 activity in all categories of malnutrition.

Long-term effects of kwashiorkor on the electroencephalogram.

The long-term effects of kwashiorkor on the electroencephalogram were assessed by means of computer analysis techniques. The experimental group, consisting of 30 black children, 6 to 12 years old, hospitalized for the treatment of kwashiorkor during the first 27 months of life, was age-matched with three control groups. These were a group of siblings and of yardmates, neither of whom had been exposed to acute infantile malnutrition, and a very high socioeconomic group of white children. The results revealed significantly less alpha activity and more slow-wave activity in the electroencephalogram of the kwashiokor group than in those of the control groups. These findings confirmed previous results based on visual analysis procedures.

Height, weight, and head circumference in survivors of marasmus and kwashiorkor.

The physical growth of 44 survivors of marasmus and 43 survivors of kwashiorker 7 1/2 years after their hospitalization and cure from malnutrition has been evaluated. The collected data on height, weight, and head circumference of these 87 previously malnourished children have been compared with data on height, weight, and head circumference of 559 children of the same age and sex from the same environment who have never been malnourished. The statistical analysis of the data indicate the following conclusions. 1) The survivors of marasmus are shorter and lighter and have a smaller head circumference than controls. The observed difference is statistically significant. 2) The survivors of kwashiorkor have the same physical stature as controls. 3) The survivors of marasmus are shorter and lighter and have a smaller head circumference than survivors of kwashiorkor. 4) The survivors of marasmus who were hospitalized for treatment of malnutrition when younger than 1 year have the same physical stature as the survivors of marasmus who were hospitalized for treatment of malnutrition when older than 1 year.

Exocrine pancreatic function and protein-calorie malnutrition in Dakar and Abidjan (West Africa): silent pancreatic insufficiency.

Pancreatic function was measured by duodenal aspiration after injection of secretin and cholecystokinin in malnourished children from Dakar and Abidjan, West Africa, and in age- and sex-matched control subjects from Dakar, Abidjan, and Marseille, France. Compared with French control subjects, pancreatic function was moderately decreased in Abidjan control subjects and more severely in Abidjan subjects with kwashiorkor. Pancreatic insufficiency was as severe in patients as in control subjects in Dakar. After a well-balanced diet was fed for 5 d, all kwashiorkor symptoms disappeared. In Abidjan pancreatic secretion levels increased but remained lower than in control subjects. After 28 d feeding, the pancreatic secretion of kwashiorkor patients in Dakar was not modified. Pancreatic extracts had no effect on changes in pancreatic insufficiency after feeding. In West Africa there is a latent pancreatic insufficiency involving water, electrolytes, and enzymes, which is more severe in Dakar, where, in contrast to Abidjan, it is neither aggravated by kwashiorkor nor corrected by feeding.

Hemodynamic findings during treatment of protein-calorie malnutrition.

Several hemodynamic parameters were sequentially determined at rest in 19 African children recovering from marasmic kwashiorkor. Before treatment, the red cell volume averaged 160 ml, the circulation time: 6.6 sec, the cardiac output: 1.00 liter/min, the stroke volume: 9.7 ml/beat, the systemic vascular resistances: 79 units and the arteriovenous differences in blood oxygen content 5.1 volume %. On the 20th realimentation day, red cell volume averaged 169 ml, the circulation time: 5.8 sec, the cardiac output: 1.38 liter/min, the stroke volume: 11.4 ml/beat, systemic vascular resistances: 62 units and arteriovenous difference: 4.2 volume %. On the 60th realimentation day, red cell volume averaged 208 ml, circulation time: 5.6 sec, cardiac output: 1.53 liter/min, stroke volume: 11.8 ml/beat, systemic vascular resistances: 56 units and arteriovenous differences: 4.1 volume%; both red cell volume and stroke volume were still significantly lower than in the control group. The children recovering from marasmic kwashiorkor showed a rapid transition from a hypocirculatory state into a near normal circulatory state with delayed increase in both red cell volume and stroke volume.

Hemodynamic findings in servere protein-calorie malnutrition.

This study was undertaken because circulatory distrubances had been advanced as a possible cause of death during initial renourishing of protein-calorie deprived children. Body weight, plasma albumin concentration, intravascular volumes (radiochromium), cardiac index (dye dilution technique), intravascular pressures (flow-guided catheterization), and related hemodynamic parameters were determined at rest in 43 infection-free African children with a form of protein-calorie malnutrition known as marasmic kwashiokor, and were compared with values observed in 24 convalescent children. The malnourished children showed a prolonged circulation time with a tendency to bradycardia and hypotension; cardiac index, stroke index, and heart work were significantly reduced, as were the intravascular volumes. Hemodynamic data correlated with either body weight or plasma albumin and cardiac index bore a direct relation to red cell volume. In the most severely malnourished subjects, ventricle filling pressures were low and vascular resistances were high. It is inferred that most patients were in an adaptive hypocirculatory state comparable to hypothroidism, while the most severely malnourished children showed frank peripheral circulatory failure comparable to hypovolemic shock. Circulatory failure on admission was associated with high death rate during treatment but the relation between cause and effect could not be clearly demonstrated.

Prevalence of HIV-1 infection and symptomatology of AIDS in severely malnourished children in Dar Es Salaam, Tanzania.

In Dar es Salaam, Tanzania, 200 children with severe malnutrition and controls matched for age, sex, and area of residence were screened for serological evidence of infection with the human immunodeficiency virus type 1 (HIV-1) over 5 months in 1988. The prevalence of HIV-1 antibodies in the malnourished group was 25.5% (51 of 200) compared with 1.5% (three of 200) in the controls. The seroprevalence rate was equally high in malnourished children above the age of 18 months (26 of 102; 25.5%), as in those below this age (25 of 98; 25.5%). The prevalence rate was higher in children with marasmus (38.2%) as compared to children with marasmic-kwashiorkor (12.3%) or kwashiorkor (12.2%). The prevalence of clinical features known to be associated with AIDS was higher in the HIV seropositive malnourished children as compared to the seronegative children. The modified World Health Organization clinical case definition of AIDS in children was also evaluated and found to have a low sensitivity and positive predictive value (62.8 and 57.1%, respectively) but a fairly high specificity (83.9%). It is recommended to routinely rule out HIV infection in malnourished children, especially those with marasmus.

Protein energy malnutrition and the nervous system.

Protein-energy malnutrition (PEM), a natural ramification of poverty, continues to be a perennial source of concern to a large segment of the world population. The developing nervous system of a child is specially vulnerable to deprivations in nurture. Peripheral nerve and muscle derangements are clinically evident by weakness, hypotonia and hyporeflexia in accordance with severity and duration of PEM. Motor and sensory nerve conduction studies exhibit significant abnormalities and often furnish useful and ominous correlation with grades of PEM. The human sural nerve histology in cases of severe PEM is characterized by persistence of small myelinated fibres, striking failure of internodal elongation and significant segmental demyelination. Young rhesus monkeys are ideal experimental PEM models and they show myopathic EMG changes amenable to rehabilitation. Muscle pathology comprises obliteration of cross-striations, streaming of Z bands, increased interfibrillary spaces, mitochondriomegaly and small-for-age fibres. Radioisotope assays reveal anomalous incorporation into various nerve and muscle constituents. Central nervous system, specially the neuropsychological functions are affected in a lasting manner. Learning deficits, behavioural problems and manual indexterity are most obtrusive features.

A study of enocrine function in protein-energy malnutrition.

Serum concentration of cortisol, growth hormone, thyroxine, thyroid stimulating hormone, follicle stimulating hormone and luteinising hormone, together with triiodothyronine uptake have been measured in Nigerian children with kwashiorkor and marasmus and compared with controls. In both types of malnutrition the cortisol and growth hormone concentrations are raised, whereas those of thyroxine and thyroid stimulating hormone are lowered compared with the controls. Triiodothyronine uptake is lowered in malnutrition but there is no apparent effect on follicle stimulating hormone or luteinising hormone in this age group.

Rehabilitating the severely malnourished infant and child.

The failure of public health measures to control protein-energy malnutrition means that continued therapeutic, curative programs for the rehabilitation of severely malnourished infants and children will be needed for the foreseeable future. Successful rehabilitation requires an understanding of the biology of malnutrition and of the dietary guidelines for provision of appropriate formulas. It is important to recognize that protein-energy malnutrition represents a metabolically and physiologically adapted state but that full recuperation entails compensatory weight gain for recovery of the expected weight for height and body composition. Overzealous early feeding is to be avoided; protein- and energy-rich diets must be introduced gradually and sustained to provide the nutrients necessary for rapid catch-up growth. Therapy involves a three-stage process of addressing acute problems, restoring nutrient balance, and ensuring nutritional rehabilitation. Despite intestinal changes due to malnutrition, intact milk provides a suitable protein source for formulation of recovery diets. As long as protein-energy malnutrition remains prevalent, research to improve its treatment will remain a high investigative priority.

Growth in length of children recovering from severe malnutrition.

The linear growth of 369 children treated for severe malnutrition at the Tropical Metabolism Research Unit, University Hospital of the West Indies, was examined retrospectively. Mean age was 12.6 months and 58 per cent of the children were oedematous on admission. Mean length for age was the same at admission and discharge (SD score - 3.4). Therefore when the sample is considered as a whole there was no catch-up in length for age. A sub-group of 108 children began to show catch-up growth in length. This sub-group did not differ in age or sex from the total sample but contained a greater proportion of non-oedematous children. Children in the sub-group were also more stunted initially (P less than 0.0001) than the group as a whole. The absolute rate of linear growth was similar in oedematous and non-oedematous children. Change in length for age during recovery was significantly less in children who were oedematous on admission. Two-thirds of the children attained at least 85 per cent weight for length before they began to increase in length. Thus in most cases linear growth followed replenishment of body weight. The data point to the need for further investigations to determine why some children were capable of early catch-up growth in length while others, with similar characteristics, showed minimal or no linear growth during recovery.

Ultrasonographic gastric emptying in protein energy malnutrition: effect of type of meal and nutritional recovery.

OBJECTIVE AND DESIGN: The earlier reports of disturbed gastric motility in protein energy malnutrition (PEM) point out to its possible contribution in the difficulties faced during nutritional rehabilitation. This study was thus designed to assess the ultrasonographic gastric emptying time (GET) using 20 ml/kg body weight of both liquid and semisolid meals, in 27 patients suffering from PEM as well as in 15 healthy matching infants to delineate any defect present, its degree in different types of PEM and the effect of nutritional rehabilitation. PATIENTS: The patients were recruited from the in-patient department of Children's Hospital, Ain Shams University, Cairo, Egypt. They were divided into three groups: 10 marasmic infants, 10 marasmic kwashiorkor (marasmic KWO) and seven kwashiorkor (KWO) cases. Ultrasonographic GET assessment was carried out within 72 h of admission and 30+/-7 days after nutritional rehabilitation. RESULTS: The gastric half-emptying time T(1/2) of both liquid and semisolid meals was markedly prolonged in patients with marasmus and marasmic KWO. It was more delayed for the semisolid than the liquid meals. This delay was reversible after nutritional rehabilitation of the patients, indicating that it was secondary to the malnourished status. On the other hand, T(1/2) of both liquid and semisolid meals showed no statistically significant delay in the KWO group and nutritional rehabilitation added no further to the results. CONCLUSION: PEM, especially marasmus and marasmic KWO, causes a delay in GET, which is reversible on nutritional recovery. This must be considered during nutritional rehabilitation of such patients to decrease the duration of their hospitalization and thus decrease the morbidity in PEM.