Animal Models of Undernutrition and Enteropathy as Tools for Assessment of Nutritional Intervention.

: Undernutrition is a major public health problem leading to 1 in 5 of all deaths in children under 5 years. Undernutrition leads to growth stunting and/or wasting and is often associated with environmental enteric dysfunction (EED). EED mechanisms leading to growth failure include intestinal hyperpermeability, villus blunting, malabsorption and gut inflammation. As non-invasive methods for investigating gut function in undernourished children are limited, pre-clinical models are relevant to elucidating the pathophysiological processes involved in undernutrition and EED, and to identifying novel therapeutic strategies. In many published models, undernutrition was induced using protein or micronutrient deficient diets, but these experimental models were not associated with EED. Enteropathy models mainly used gastrointestinal injury triggers. These models are presented in this review. We found only a few studies investigating the combination of undernutrition and enteropathy. This highlights the need for further developments to establish an experimental model reproducing the impact of undernutrition and enteropathy on growth, intestinal hyperpermeability and inflammation, that could be suitable for preclinical evaluation of innovative therapeutic intervention.

Alimentación neonatal asociada a sobrepeso y obesidad en niños y adolescentes de Cuenca, Ecuador / Neonatal feeding associated with overweight and obesity in children and adolescents of Cuenca, Ecuador

Introducción: La alimentación inadecuada en la etapa neonatal se asocia con la aparición de enfermedades metabólicas en períodos ontogenéticos posteriores. Objetivo: Asociar la lactancia materna y el destete con el sobrepeso y obesidad en niños y adolescentes de la Unidad Educativa César Dávila Andrade, Cuenca, Ecuador, en el período de octubre de 2016 a marzo de 2017. Materiales y Métodos: Se realizó un estudio observacional de tipo descriptivo durante el período noviembre 2016 a enero 2017 en el Cantón Cuenca, provincia Azuay, Ecuador. El muestreo probabilístico por conglomerados de iguales proporciones seleccionó 137 niños y adolescentes entre 5 y 18 años de edad. Se aplicó un cuestionario que recogió datos sociodemográficos, de lactancia materna y destete. Se realizaron mediciones de peso y talla, y el cálculo del índice de Masa Corporal. Se procesaron los datos mediante estadística descriptiva (media y desviación estándar), inferencial (Prueba T y X2) y correlaciones bivariada (X2, odds ratio) y multivariada (regresión logística binaria) mediante SPSS 23.0. Resultados: La lactancia materna por menos de 6 meses, la introducción de alimentos de manera temprana y la actividad física leve incrementan el riesgo de sobrepeso y obesidad en más de 3 veces cada una en niños y adolescentes. Conclusiones: La lactancia materna y el destete están asociadas al sobrepeso y obesidad desde etapas tempranas del desarrollo humano. El valor explicativo que tienen en niños y adolescentes es relevante, y sugiere su empleo en programas educativos y preventivos en salud(AU)

Introduction: Inadequate feeding in the neonatal stage is associated with the appearance of metabolic diseases in further ontogenetic periods. Objective: To associate breastfeeding and weaning with overweight and obesity in children and adolescents in the Educational Unit César Dávila Andrade in the Cuenca region, Ecuador, from October 2016 to March 2017. Material and Methods: A descriptive, associative, and empirical study was conducted during the period of November 2016 - January 2017 in Cuenca, province of Azuay, Ecuador. The probability sampling by conglomerates of equal proportions selected 137 children and adolescents from 5 to 18 years of age. A questionnaire that collected sociodemographic data about breastfeeding and weaning was applied. Measurements of weight and height were made, as well as the calculation of the Body Mass Index. The data were processed by descriptive statistics (mean, standard deviation); inferential statistics (T Test, X2); bivariate correlations (X2, odds ratio), and binary logistic regression, using SPSS 23.0. Results: Breastfeeding for less than six months, the introduction of food at an early stage of the life, and mild physical activity are factors that increase the risk of overweight and obesity more than 3 times in children and adolescents. Conclusions: Breastfeeding and weaning are associated with overweight and obesity from early stages of human development. The explanatory value that children and adolescents have is relevant, suggesting its implementation in educational and preventive health programs(AU)

Indigenous food ingredients for complementary food formulations to combat infant malnutrition in Benin: a review.

This paper reviews indigenous Beninese food resources as potential ingredients for complementary infant foods with the aim to develop affordable formulations for low-income households in each agro-ecological zone of the country. Potential ingredients were selected on their documented nutritional value. The selected foods encompass 347 food resources, namely 297 plant products from home gardens or collected from natural vegetation and 50 animals, either domesticated or from the wild. The compiled data reveal that the distribution of the available food resources was unbalanced between agro-ecological zones. Only a few animal ingredients are obtainable in northern Benin. Most resources are seasonal, but their availability may be extended. A high variation was observed in energy and nutrient contents. Antinutritional factors were identified in some resources, but processing techniques were reported to reduce their presence in meals. In general, ingredients from local tree foods (Adansonia digitata, Parkia biglobosa) were adequate as sources of nutrients for complementary infant foods. Based on this review, local foods for the development of complementary food formulas for Beninese infants and children may be selected for each agro-ecological zone. The approach used is exemplary for other sub-Saharan African countries in need of complementary infant foods. © 2017 Society of Chemical Industry.

Stable C and N isotope analysis of hair suggest undernourishment as a factor in the death of a mummified girl from late 19th century San Francisco, CA.

The chance discovery of a 1.5-3.5 years old mummified girl presents a unique opportunity to further our understanding of health and disease among children in 19th Century San Francisco. This study focuses on carbon and nitrogen stable isotope signatures in serial samples of hair that cover the last 14 months of her life. Results suggest an initial omnivorous diet with little input from marine resources or C4 plants. Around six months before death δ15N starts a steady increase, with a noticeable acceleration just two months before she died. The magnitude of δ15N change, +1.5‰ in total, is consistent with severe undernourishment or starvation. Cemetery records from this time period in San Francisco indicate high rates of infant and child mortality, mainly due to bacterial-borne infectious diseases, about two orders of magnitude higher than today. Taken together, we hypothesize that the girl died after a prolonged battle with such an illness. Results highlight the tremendous impacts that modern sanitation and medicine have had since the 1800s on human health and lifespan in the United States.

Assessment of Regression Models for Adjustment of Iron Status Biomarkers for Inflammation in Children with Moderate Acute Malnutrition in Burkina Faso.

BACKGROUND: Biomarkers of iron status are affected by inflammation. In order to interpret them in individuals with inflammation, the use of correction factors (CFs) has been proposed. OBJECTIVE: The objective of this study was to investigate the use of regression models as an alternative to the CF approach. METHODS: Morbidity data were collected during clinical examinations with morbidity recalls in a cross-sectional study in children aged 6-23 mo with moderate acute malnutrition. C-reactive protein (CRP), α1-acid glycoprotein (AGP), serum ferritin (SF), and soluble transferrin receptor (sTfR) were measured in serum. Generalized additive, quadratic, and linear models were used to model the relation between SF and sTfR as outcomes and CRP and AGP as categorical variables (model 1; equivalent to the CF approach), CRP and AGP as continuous variables (model 2), or CRP and AGP as continuous variables and morbidity covariates (model 3) as predictors. The predictive performance of the models was compared with the use of 10-fold crossvalidation and quantified with the use of root mean square errors (RMSEs). SF and sTfR were adjusted with the use of regression coefficients from linear models. RESULTS: Crossvalidation revealed no advantage to using generalized additive or quadratic models over linear models in terms of the RMSE. Linear model 3 performed better than models 2 and 1. Furthermore, we found no difference in CFs for adjusting SF and those from a previous meta-analysis. Adjustment of SF and sTfR with the use of the best-performing model led to a 17% point increase and <1% point decrease, respectively, in estimated prevalence of iron deficiency. CONCLUSION: Regression analysis is an alternative to adjust SF and may be preferable in research settings, because it can take morbidity and severity of inflammation into account. In clinical settings, the CF approach may be more practical. There is no benefit from adjusting sTfR. This trial was registered at www.controlled-trials.com as ISRCTN42569496.

Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children.

Undernourished children exhibit impaired development of their gut microbiota. Transplanting microbiota from 6- and 18-month-old healthy or undernourished Malawian donors into young germ-free mice that were fed a Malawian diet revealed that immature microbiota from undernourished infants and children transmit impaired growth phenotypes. The representation of several age-discriminatory taxa in recipient animals correlated with lean body mass gain; liver, muscle, and brain metabolism; and bone morphology. Mice were cohoused shortly after receiving microbiota from healthy or severely stunted and underweight infants; age- and growth-discriminatory taxa from the microbiota of the former were able to invade that of the latter, which prevented growth impairments in recipient animals. Adding two invasive species, Ruminococcus gnavus and Clostridium symbiosum, to the microbiota from undernourished donors also ameliorated growth and metabolic abnormalities in recipient animals. These results provide evidence that microbiota immaturity is causally related to undernutrition and reveal potential therapeutic targets and agents.

Environmental Enteropathy, Oral Vaccine Failure and Growth Faltering in Infants in Bangladesh.

BACKGROUND: Environmental enteropathy (EE) is a subclinical enteric condition found in low-income countries that is characterized by intestinal inflammation, reduced intestinal absorption, and gut barrier dysfunction. We aimed to assess if EE impairs the success of oral polio and rotavirus vaccines in infants in Bangladesh. METHODS: We conducted a prospective observational study of 700 infants from an urban slum of Dhaka, Bangladesh from May 2011 to November 2014. Infants were enrolled in the first week of life and followed to age one year through biweekly home visits with EPI vaccines administered and growth monitored. EE was operationally defied as enteric inflammation measured by any one of the fecal biomarkers reg1B, alpha-1-antitrypsin, MPO, calprotectin, or neopterin. Oral polio vaccine success was evaluated by immunogenicity, and rotavirus vaccine response was evaluated by immunogenicity and protection from disease. This study is registered with ClinicalTrials.gov, number NCT01375647. FINDINGS: EE was present in greater than 80% of infants by 12 weeks of age. Oral poliovirus and rotavirus vaccines failed in 20.2% and 68.5% of the infants respectively, and 28.6% were malnourished (HAZ < - 2) at one year of age. In contrast, 0%, 9.0%, 7.9% and 3.8% of infants lacked protective levels of antibody from tetanus, Haemophilus influenzae type b, diphtheria and measles vaccines respectively. EE was negatively associated with oral polio and rotavirus response but not parenteral vaccine immunogenicity. Biomarkers of systemic inflammation and measures of maternal health were additionally predictive of both oral vaccine failure and malnutrition. The selected biomarkers from multivariable analysis accounted for 46.3% variation in delta HAZ. 24% of Rotarix® IgA positive individuals can be attributed to the selected biomarkers. INTERPRETATION: EE as well as systemic inflammation and poor maternal health were associated with oral but not parenteral vaccine underperformance and risk for future growth faltering. These results offer a potential explanation for the burden of these problems in low-income problems, allow early identification of infants at risk, and suggest pathways for intervention. FUNDING: The Bill and Melinda Gates Foundation (OPP1017093).

Effect of fetal and infant malnutrition on metabolism in older age.

BACKGROUND: While malnutrition is an important concern in the developing world, Western countries are experiencing a pandemic of obesity and metabolic diseases. OBJECTIVE: This work reviews the current state of knowledge of the effects of malnutrition during early life on metabolism in older age. METHODS: The impact of early-life determinants on diabetes and related metabolic diseases in later life is elucidated by three different methodological approaches. First, results from animal studies in dietary manipulation models are reviewed. Second, findings from epidemiological studies that often use natural experiments to determine the effects of famines on the health status of the population are discussed. Finally, the relation between maternal or childhood malnutrition and diabetes in adulthood is explored in a big-data study using the entire population of a country across a century. RESULTS: We present overwhelming evidence that the maternal or early childhood nutritional status negatively affects both the short- and long-term health status and development of the offspring, thereby providing starting points to formulate intervention and prevention strategies. In particular, it was found that in the case of early-life exposure to famine, the risk of the offspring to develop type 2 diabetes in older age is up to 125% higher than without famine exposure. CONCLUSION: Due to its inherent complexity, an understanding of the long-term effects of maternal and childhood malnutrition on metabolism in older age necessitates interdisciplinary and big-data approaches. Only then can we hope to prevent chronic diseases at their earliest beginning.

Metabolomics and fetal-neonatal nutrition: between "not enough" and "too much".

Metabolomics is a new analytical technique defined as the study of the complex system of metabolites that is capable of describing the biochemical phenotype of a biological system. In recent years the literature has shown an increasing interest in paediatric obesity and the onset of diabetes and the metabolic syndrome in adulthood. Some studies show that fetal malnutrition, both excessive and insufficient, may permanently alter the metabolic processes of the fetus and increase the risk of future chronic pathologies. At present then, attention is being focused mainly on the formulation of new hypotheses, by means of metabolomics, concerning the biological mechanisms to departure from fetal-neonatal life that may predispose to the development of these diseases.

Effects of neonatal programming on hypothalamic mechanisms controlling energy balance.

The prevalence of overweight and obesity in most developed countries has markedly increased during the last decades. In addition to genetic, hormonal, and metabolic influences, environmental factors like fetal and neonatal nutrition play key roles in the development of obesity. Interestingly, overweight during critical developmental periods of fetal and/or neonatal life has been demonstrated to increase the risk of obesity throughout juvenile life into adulthood. In spite of this evidence, the specific mechanisms underlying this fetal/neonatal programming are not perfectly understood. However, it is clear that circulating hormones such as insulin and leptin play a critical role in the development and programming of hypothalamic circuits regulating energy balance. Here, we review what is currently known about the impact of perinatal malnutrition on the mechanisms regulating body weight homeostasis. Understanding these molecular mechanisms may provide new targets for the treatment of obesity.

High increments of overweight along with low length-for-age growth during the first 24 months of life / Aumento de sobrepeso con bajo crecimiento de talla-para-edad durante los primeros 24 meses de vida

Background: It has been reported that children nursed in orphanages loose one month of lineal growth for every three months they spend in the orphanage. Objective: The purpose of this study was to evaluate the daily variation of weight- for- length and length-for-age among infants under 24 months of age, living in a temporary public orphanage in Mexico. Methods: Ninety children from 0 to 24 months of age, who were institutionalized at an orphanage, were assessed during a three month period. Upon arrival their height and weight were measured daily, Monday through Friday. Daily growth velocity for weight and length was calculated. Length-for age (LAZ) and weight-for-length (WHZ) age z- scores were calculated based on WHO criteria. Risk of overweight (ROW) and overweight (OW) were classified using the WHO criteria. Results: The increments of daily weight were lower than the normal range (9 g daily), but the ROW and OW increased from 10% and 3% at the beginning of the study to 14% and 11% at the end. At the end of the follow-up, WHZ was inversely associated to length (cm/day) velocity (r = -302, p < 0.01). Although a significant increase in ROW and OW was observed, at the end of the study, 31% of the children showed signs of stunting (-2 SD in length-age) and 5% remained emaciated (-2 SD in weight-length). Conclusions: Children living in an orphanage showed reduced increments of weight and length-for-age, as well as a reduced length velocity and an increased ROW and OW (AU)

Antecedentes: Se ha descrito que los niños de orfanatorios pierden un mes lineal por cada tres meses que residen en un orfanatorio. Objetivo: El propósito de este estudio fue evaluar la variación diaria de peso-para-talla y talla-para edad, entre infantes de menos de 24 meses de edad, que residen en un orfanatorio público temporal de México Métodos: Se valoraron durante un período de tres meses, noventa niños de 0 a 24 meses de edad, institucionalizados en un orfanatorio. Desde su ingreso se midieron diariamente la estatura y el peso de manera estandarizada, del lunes al viernes. Se calculó la velocidad de crecimiento diario del peso y la estatura. Las puntuaciones del z-score de la talla-para-edad y del peso-para-talla (zPT), se calcularon basados en los criterios de la OMS. El riesgo de sobrepeso (RSP) y el sobrepeso (SP) se clasificó de acuerdo a los criterios recomendados por la OMS. Resultados: Los aumentos diarios de peso fueron menores que el rango normal para la edad (9 g diarios), pero el RSP y el SP aumentó de 10 a 3% al inicio del estudio, a 14 y 11% al final del estudio. Al final del seguimiento, el zPT estuvo inversamente asociado a la velocidad de crecimiento (cm/dia) lineal (r = -302, p < 0,01). Aunque se observó un aumento significativo de RSP y SP, al final del estudio 31% de los niños presentaban signos de retraso de crecimiento (-2 SD de talla-para-edad) y 5% seguían emaciados (-2 SD de peso-para-edad). Conclusiones: Los niños que viven en orfanatos presentan aumentos reducidos de peso y talla para la edad, reducción de la velocidad de crecimiento lineal y un aumento de RSP y SP (AU)

Role of calcium deficiency in development of nutritional rickets in Indian children: a case control study.

CONTEXT: Nutritional rickets is usually attributed to vitamin D deficiency. Studies from some tropical countries have postulated low dietary intake of calcium as the cause of nutritional rickets. Both vitamin D and dietary calcium deficiency are highly prevalent in India. Information on their relative contribution in the development of rickets in Indian children is limited. OBJECTIVE: The aim was to study the role of calcium and vitamin D deficiency in causation of nutritional rickets in young Indian children. DESIGN AND METHODS: In a case-control study, 67 children with nutritional rickets and 68 age- and sex-matched healthy controls were compared for demographic factors, nutritional status, sun exposure (UV score), dietary calcium and phytate intake (for subjects not breast-fed at presentation), and biochemical parameters [serum calcium, inorganic phosphate, alkaline phosphatase, 25-hydroxyvitamin D (25OHD), and PTH]. RESULTS: Mean intake of calcium (204±129 vs. 453±234 mg/d; P<0.001) and proportion of calcium from dairy sources (41.7 vs. 88.6%; P<0.001) were significantly lower in cases vs. controls. The dietary intake of phytate was also significantly higher in cases (P=0.01). Median serum 25OHD level (interquartile range) in both cases and controls was in the range of deficiency [13.7 (10; 17.9) and 19.4 (12.3; 24.6) ng/ml, respectively]. There was no significant difference in the serum 25OHD level (P=0.08) or sun exposure as measured by UV score (P=0.39) among the cases and controls. In cases with rickets, significant negative correlations were seen between dietary calcium intake and radiological score (r=-0.28; P=0.03) and PTH (r=-0.26; P=0.02). No correlation was found between serum 25OHD level and radiological score or biochemical parameters of rickets. CONCLUSIONS: Rickets develops when low dietary calcium intake coexists with a low or borderline vitamin D nutrition status.

[Fecal calprotectin levels in preterm infants during the early neonatal period].

OBJECTIVE: To explore whether fecal calprotectin (f-calprotectin, FC) may be an early marker for the identification of gastrointestinal injury in preterm infants by measuring FC concentration and changes of FC concentration in infants with different perinatal factors. METHODS: FC concentration was measured using ELISA in 76 samples (50-100 mg) obtained from 38 preterm infants (gestation 29 to 33 weeks), at birth and on the third day after birth (the 1st and the 2nd FC levels). The infants were classified into three groups according to the reason for preterm birth: premature rupture of membranes (PROM; n=13), spontaneous preterm birth (SPB; n=5) and indicated preterm birth (IPB; n=20). RESULTS: There were no significant differences between the 1st and 2nd FC levels in the 38 infants. The 1st FC level in the PROM group was significantly higher than that in the IPB group (P<0.05). The 1st FC level in infants whose mothers received antenatal antibiotics treatment was significantly lower. Infants born by cesarean section had a significantly lower 1st FC level than those born by vaginal delivery (P<0.05). Both the 1st and 2nd FC levels in infants with feeding intolerance were significantly higher than in infants with feeding tolerance (P<0.05). The 2nd FC level was negatively correlated with 1 min Apgar score (r=-0.3, P<0.05). CONCLUSIONS: Premature rupture of membranes and perinatal asphyxia may lead to an increase in the excretion of FC in preterm infants. FC may be used as a marker for early evaluation of gastrointestinal conditions in preterm infants.

Dietary cysteine is used more efficiently by children with severe acute malnutrition with edema compared with those without edema.

BACKGROUND: Children with edematous severe acute malnutrition (SAM) produce less cysteine than do their nonedematous counterparts. They also have marked glutathione (GSH) depletion, hair loss, skin erosion, gut mucosal atrophy, and depletion of mucins. Because GSH, skin, hair, mucosal, and mucin proteins are rich in cysteine, we hypothesized that splanchnic extraction and the efficiency of cysteine utilization would be greater in edematous than in nonedematous SAM. OBJECTIVE: We aimed to measure cysteine kinetics in childhood edematous and nonedematous SAM. DESIGN: Cysteine flux, oxidation, balance, and splanchnic uptake (SPU) were measured in 2 groups of children with edematous (n = 9) and nonedematous (n = 10) SAM at 4.4 ± 1.1 d after admission (stage 1) and at 20.5 ± 1.6 d after admission (stage 2) when they had replenished 50% of their weight deficit. RESULTS: In comparison with the nonedematous group, the edematous group had slower cysteine flux at stage 1 but not at stage 2; furthermore, they oxidized less cysteine at both stages, resulting in better cysteine balance and therefore better efficiency of utilization of dietary cysteine. Cysteine SPU was not different between groups but was ∼45% in both groups at the 2 stages. CONCLUSION: These findings suggest that children with edematous SAM may have a greater requirement for cysteine during early and mid-nutritional rehabilitation because they used dietary cysteine more efficiently than did their nonedematous counterparts and because the splanchnic tissues of all children with SAM have a relatively high requirement for cysteine. This trial was registered at clinicaltrials.gov as NCT00069134.

Weight gain and metabolic complications in preterm infants with nutritional support.

OBJECTIVE: To analyze the weight gain and to describe the metabolic complications in preterm newborns with nutritional support (NS) and to describe nutritional practices in the first month of hospitalization for 52 preterm newborns. MATERIAL AND METHODS: Descriptive and prospective study of preterm infants (30-36 gestational weeks), with birth weight > 1 kg, hospital stay > 12 days, without respiratory support or complications, conducted at a public hospital in Leon, Guanajuato, Mexico from January to November 2006. Weight, serum glucose, insulin, cholesterol, triglycerides, gamma-glutamyltransferase, creatinine, urea nitrogen, type of NS (parenteral PN, enteral EN, mixed MN), energy content, and macronutrient intake were measured weekly. To obtain representative data, nutritional practices were not altered by the study protocol. One way ANOVA and Wilcoxon tests were used in data analyses. RESULTS: Overall, 52 newborns were included, averaging 33 gestational weeks and 1,590 g of weight. The NS was started by the fourth day on average. Parenteral nutrition was the most frequent NS during the first 2 weeks (75%). Energy and macronutrient supply was 50% less than the recommended. Weight gain ranged from -100 to 130 g/week. Parenteral nutrition showed better weekly weight gain, followed by EN. The metabolic complication rate per person-day was greater for MN (0.56), than for EN (0.16) or PN (0.09). Routine surveillance of weight and metabolic complications was deficient. CONCLUSIONS: Late onset of NS, insufficient energy supply, and deficient surveillance were obstacles to weight gain and to prevent the metabolic complications in these newborns.

Peptides from adipose tissue in monitoring energy balance in infants.

BACKGROUND/AIM: Overnutrition as well as undernutrition is a serious problem in hospitalized patients, especially in infants. Routine laboratory tests detecting disturbances in energy balance are not specific or accurate. The aim of this study was to evaluate adiponectin and leptin as markers of short-time energy malnutrition. METHODS: Forty-five infants fed orally and parenterally were included in the study. Plasma glucose, leptin and adiponectin were measured in a fasting state and postprandially (1 h after the meal), after a minimum of 24 h of total parenteral nutrition (TPN) and after a minimum of 8 h of intravenous infusion of glucose and crystalloids. RESULTS: Postprandial glucose levels in children fed orally was similar to that observed in children who received intravenous infusion of glucose. The TPN children had slightly higher glucose concentration in contrast to leptin levels which were significantly lower in this group (1.08 mg/mL +/- 0.43) as compared to the others (p < 0.05 in both cases). The mean postprandial levels of the adiponectin in orally fed children were significantly higher (10.7 microg/mL +/- 2.4) than in children with TPN (5.8 microg/mL +/- 2.4; p < 0.001) and in children hydrated intravenously (3.3 microg/mL +/- 2.3; p < 0.001). The concentration of adiponectin correlated significantly with calorie intake. CONCLUSIONS: Oral meal does not affect the plasma concentrations of leptin and adiponectin in infants. Adiponectin is a good short-time marker of energy malnutrition in infants.

Tyrosine requirement during the rapid catch-up growth phase of recovery from severe childhood undernutrition.

The requirement for aromatic amino acids during the rapid catch-up in weight phase of recovery from severe childhood undernutrition (SCU) is not clearly established. As a first step, the present study aimed to estimate the tyrosine requirement of children with SCU during the catch-up growth phase of nutritional rehabilitation using a diet enriched in energy and proteins. Tyrosine requirement was calculated from the rate of excretion of ¹³CO2 (F ¹³CO2) during [¹³C]phenylalanine infusion in thirteen children with SCU, five females and eight males, at about 19 d after admission when the subjects were considered to have entered their rapid catch-up growth phase and were consuming 627.3 kJ and about 3.5 g protein/kg per d. Measurements of F ¹³CO2 during [¹³C]phenylalanine infusion were made on two separate days with a 1 d interval. Three measurements at tyrosine intakes of 48, 71 and 95 mg/kg per d were performed on experimental day 1 and measurements at tyrosine intakes of 148, 195 and 241 mg/kg per d were performed on experimental day 2. An estimate of the mean requirement was derived by breakpoint analysis with a two-phase linear regression cross-over model. The breakpoint, which represents an estimate of the mean tyrosine requirement, is a value of 99 mg/kg per d when the children were growing at about 15 g/kg per d. The result indicates that the mean requirement for tyrosine during the catch-up growth phase of SCU is about 99 mg/kg per d under similar conditions to the present study.

Neurochemical changes in the developing rat hippocampus during prolonged hypoglycemia.

Hypoglycemia is common during development and is associated with the risk of neurodevelopmental deficits in human infants. The effects of hypoglycemia on the developing hippocampus are poorly understood. The sequential changes in energy substrates, amino acids and phosphocreatine were measured from the hippocampus during 180 min of insulin-induced hypoglycemia (blood glucose < 2.5 mmol/L) in 14-day-old rats using in vivo(1)H NMR spectroscopy. Hypoglycemia resulted in neuroglycopenia (brain glucose < 0.5 micromol/g). However, the phosphocreatine/creatine (PCr/Cr) ratio was maintained in the physiological range until approximately 150 min of hypoglycemia, indicating that energy supply was sufficient to meet the energy demands. Lactate concentration decreased soon after the onset of neuroglycopenia. Beyond 60 min, glutamine and glutamate became the major energy substrates. A precipitous decrease in the PCr/Cr ratio, indicative of impending energy failure occurred only after significant depletion of these amino acids. Once glutamate and glutamine were significantly exhausted, aspartate became the final energy source. N-acetylaspartate concentration remained unaltered, suggesting preservation of neuronal/mitochondrial integrity during hypoglycemia. Correction of hypoglycemia normalized the PCr/Cr ratio and partially restored the amino acids to pre-hypoglycemia levels. Compensatory neurochemical changes maintain energy homeostasis during prolonged hypoglycemia in the developing hippocampus.

Perinatal copper deficiency alters rat cerebellar purkinje cell size and distribution.

Copper is required for activity of several key enzymes and for optimal mammalian development, especially within the central nervous system. Copper-deficient (CuD) animals are visibly ataxic, and previous studies in rats have demonstrated impaired motor function through behavioral experiments consistent with altered cerebellar development. Perinatal copper deficiency was produced in Holtzman rat dams by restricting dietary copper during the last two thirds of gestation and lactation. Male offspring were evaluated at postnatal day 25. Compared to cerebella from copper-adequate pups, the CuD pups had larger Purkinje cell (PC) size and irregularities in the Purkinje cell monolayer. These results suggest that the ataxic behavioral phenotype of CuD rats may result from disrupted inhibitory pathways in the cerebellum. A similar PC phenotype is seen in Menkes disease and in mottled mouse mutants with genetic copper deficiency, suggesting that copper deficiency and not just specific loss of ATP7A function is responsible.

[Biologic profile in Tunisian infants (0-2 years), malnourished]. / Profil biologique d'une population de nourrissons Tunisiens (0-2 ans), malnutris.

BACKGROUND: The malnutrition of the infants could be explained by a delay of the growth and the perturbation of biological parameters. AIM: To establish the nutritional profile of the Tunisian infant of less than two years. To specify the principal deficiencies and the possible origins of these deficiencies. METHODS: In our transverse exploratory study, carried out in period of 9 month. This study was conducted in two groups of Tunisian young children less than two years old: a control group and a malnourished group (Z score < or = 2SD). RESULTS: Our data consolidate the important impact of pregnant women nutritional state and of breastfeeding on the foetus ant infant growth.Compared to control infants, the malnourished young showed a significant alteration of different biologic parameters. This alteration appeared positively linked to the gravity of malnutrition as indicated by the positive relation obtained between the weight/height ratio and many studied parameters. The malnourished infants showed, notably, a significant reduction of the average values of Chol-HDL, apo AI, Vit E, TSH and TF4 levels and Chol-HDL/Chol LDL ratio. Chol-HDL, apo AI and HDL/Chol-LDL are found positively and significantly correlated with TF4. So, their reduction in ill children would be, at least in part, a side effect of the thyroid function reduction. CONCLUSION: Our results confirm the existence of an important change of biological profile in malnourished young children. Besides, they emphasize that studies about young children could be helpful, notably, in the prevention and the fight against atherosclerosis.