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.

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.

Definiendo el síndrome de desgaste proteico energético en la enfermedad renal crónica: prevalencia e implicaciones clínicas / Defining protein-energy wasting syndrome in chronic kidney disease: prevalence and clinical implications

La presencia de malnutrición es bien conocida en la enfermedad renal crónica (ERC). El descubrimiento en los últimos 15 años de los mecanismos fisiopatológicos que desencadenan este proceso, tales como la anorexia, el aumento del catabolismo proteico y la inflamación, ha generado la necesidad de una nueva denominación por la Sociedad Renal Internacional de Nutrición y Metabolismo (ISRNM): protein energy wasting syndrome (PEW). Los objetivos de este documento son proponer la utilización del término «desgaste proteico energético» (DPE) como una traducción más fiel del término anglosajón y actualizar los mecanismos patogénicos implicados que son inherentes al DPE. Simultáneamente revisamos las últimas evidencias epidemiológicas que ponen de manifiesto la relevancia de la malnutrición y su impacto tanto en la mortalidad como en la morbilidad en la ERC. Por último, destacamos la necesidad de redefinir los criterios diagnósticos del DPE para que sean aplicables a la población española con ERC. Los criterios establecidos por la ISRNM creemos que no son extrapolables a diferentes poblaciones, como ocurre por ejemplo con las diferencias antropométricas interraciales (AU)

The presence of malnutrition in chronic kidney disease (CKD) is well-known. The discovery in the last 15 years of pathophysiological mechanisms that lead to this process, such as anorexia, the increase of protein catabolism and inflammation, has created the need for a new name by the International Society of Renal Nutrition and Metabolism (ISRNM): protein-energy wasting syndrome (PEW). This document's objectives are to propose the use of the term "desgaste proteico energético" (DPE) as a more accurate translation of the English term and to update the pathogenic mechanisms involved that are inherent to DPE (PEW). We simultaneously review the latest epidemiological evidence that highlight the relevance of malnutrition and its impact both on mortality and morbidity in CKD. Finally, we point out the need to redefine DPE (PEW) diagnostic criteria so that they are applicable to the Spanish population with CKD. We do not think that the criteria established by the ISRNM can be extrapolated to different populations, as is the case, for example, with interracial anthropometric differences (AU)

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.

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 / Efecto de los niveles séricos de magnesio y los niveles séricos de Endotelina-1 sobre la densidad mineral osea en la malnutrición calórico-proteica

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.

El consumo inadecuado y desbalanceado de proteínas y calorías energía conduce a la malnutrición calórico-proteica (MCP). Se sabe que la densidad mineral ósea y los niveles séricos de magnesio son bajos en los ninos malnutridos. Sin embargo, no está claro el papel que desempenan los niveles séricos de magnesio y los niveles séricos de endotelina-1 (ET-1) en la patofisiología de la mineralización del hueso. Por consiguiente, las relaciones entre los niveles séricos de magnesio y los niveles séricos de ET-1, y los cambios en la densidad mineral ósea, constituyen el objeto de investigación de este estudio. Hubo un total de 32 sujetos; 25 de ellos tenían DCP y 7 eran considerados. Si bien los niveles séricos promedios de ET-1 de los ninos con kwashiorkor y marasmo no mostraron diferencia estadística significativa, los niveles séricos promedio de ET-1 de ambos grupos fueron significativamente más altos que los del grupo de control. Los niveles séricos de magnesio estuvieron por debajo del valor normal en 9 (36%) de 25 ninos malnutridos. Los ninos malnutridos incluidos en este estudio fueron divididos en dos sub-grupos según sus niveles de magnesio en suero. Mientras que los niveles séricos promedio de ET-1 en el grupo con niveles bajos de magnesio fueron significativamente más altos que los del grupo con niveles normales de magnesio (p < 0.05), la densidad mineral ósea promedio y los niveles promedio del contenido mineral óseo fueron significativamente más bajos (p < 0.05). En conclusión, muchos factores juegan un papel en la patofisiología de los cambios en la densidad mineral ósea por la malnutrición. Nuestro estudio sugirió niveles más bajos de magnesio y niveles más altos de ET-1 podrían ser factores importantes en los cambios de densidad mineral ósea en la malnutrición. Se recomienda que los pacientes malnutridos, especialmente a causa de hipomagnesemia, sean tratados con magnesio lo más pronto posible.

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.

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.

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.

Protein energy malnutrition.

Protein energy malnutrition (PEM) is a common problem worldwide and occurs in both developing and industrialized nations. In the developing world, it is frequently a result of socioeconomic, political, or environmental factors. In contrast, protein energy malnutrition in the developed world usually occurs in the context of chronic disease. There remains much variation in the criteria used to define malnutrition, with each method having its own limitations. Early recognition, prompt management, and robust follow up are critical for best outcomes in preventing and treating PEM.

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.

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.

Prevalence of HIV infection and AIDS symptomatology in malnourished children--a hospital based study.

One hundred and seventy five malnourished children aged between 1(1/2) and 12 years attending pediatric department of Regional Institute of Medical Sciences Hospital, Imphal from January 2001 to June 2002 were screened for human immunodeficiency virus (HIV) infection along with their biological mothers after pretest counselling and informed consent. The prevalence rate of HIV seropositivity among malnourished children was 21.7%. Children aged between 1(1/2) and 3 years had the highest seroprevalence (47.4%) and male to female ratio was 1.5: 1. Underweight children showed the highest seroprevalence (47.4%) and children with kwashiorkor showed least seroprevalence (10.5%). Mode of HIV transmission was vertical in 94.7%. The causative agent was HIV-I in all the cases. AIDS defining children features were seen more frequently among HIV seropositive malnourished children as compared to the seronegative children. Prolonged fever (p 0.001), oropharyngeal candidiasis (p<0.001), generalised lymphadenopathy (p<0.001) and disseminated maculopapular dermatitis (p<0.001) were significantly related to HIV infection. Among seronegative children 18.2% fulfilled the clinical criteria for AIDS and among seropositive children 94.7% had AIDS. The total mortality encountered among seropositive children was 34.2%. It is suggested to confirm findings based on larger community based data before recommending mandatory HIV testing in all malnourished children. Specific guidelines on the nutritional management of children with HIV/AIDS is needed in Manipur where HIV is spreading rapidly.

Increased oxidative stress in kwashiorkor.

To test the hypothesis that kwashiorkor is associated with increased oxidative stress, urinary concentrations of 2 oxidized amino acids, o,o '-dityrosine and ortho -tyrosine, were measured by gas chromatography-mass spectrometry. Children with kwashiorkor, with or without infection, had a 3- to 7-fold increase in urinary o,o '-dityrosine and a 1.5- to 2-fold increase in ortho -tyrosine when compared with well-nourished children. This observation raises the possibility that oxidative damage to proteins and other biologic targets plays a role in the clinical manifestations of kwashiorkor.