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Cases of neglect in dogs are among the forensic cases submitted most commonly for postmortem examination. Starvation is a form of primary protein-energy malnutrition in which the availability of food is severely restricted or absent; cachexia is a form of protein-energy malnutrition secondary to progressive metabolic derangement during chronic diseases. Despite both conditions leading to an emaciated appearance of the cadaver, discrimination between the two is crucial in forensic cases. We hypothesized that among emaciated dogs, the degree of liver atrophy in starved animals is higher than in cachectic ones, and that this can be investigated microscopically, regardless of the degree of cadaver decomposition. We studied 46 animals: 23 starved, 11 cachectic, and 12 control dogs. Portal tracts were identified by the presence of a bile duct and associated vascular structures recognizable by a thin rim of collagen still visible regardless of the degree of cadaver decomposition. The number of portal tracts per lpf (10×) was used as an indirect measure of atrophy. The number of portal tracts in starved dogs was significantly higher ( p < 0.01) compared to both cachectic and control dogs, indicating a higher degree of liver atrophy in starvation. Measuring the density of portal tracts offers a reliable additional tool for discrimination between starvation and cachexia.

Protein malnutrition (PMN) is a global health issue but most prevalent in Africa and Asia. It exerts detrimental effect on structural and physiological aspects of hippocampal circuitry. Despite accumulating evidence for PMN induced changes in nervous system, relatively very little is known about how maternal nutritional supplementation during malnutrition affects glial cells and neurons. Herein, we aimed to investigate the effects of maternal Spirulina supplementation against PMN induced oxidative stress, reactive gliosis and neuronal damage in hippocampus of F1 progeny. Three months old healthy Sprague Dawley females (n = 24) were shifted to normoprotein (NC; 20% protein) and low protein (LP; 8% protein) diets 15 days before conception. The NC and LP group females were subdivided into two groups according to Spirulina supplementation (400 mg/kg/b.wt. orally throughout gestation and lactation period): normal control with Spirulina (NC SPI) and low protein with Spirulina supplemented group (LP SPI). F1 progeny born were used in present study. Thus, building on earlier results of ameliorated neurobehavioral and cognitive abilities in Spirulina supplemented protein deprived rats, the present study incorporates neurochemical and morphometric analysis of glial cells and neurons and revealed that maternal Spirulina consumption partially prevented the PMN associated neuropathological alterations in terms of attenuated oxidative brain damage, reduced reactive gliosis and apoptotic cell population, improved dendritic branch complexity with few damaged neurons and enhanced mushroom shaped spine density. The results suggest that cellular changes in hippocampus after PMN are partially restored after maternal Spirulina supplementation and one could envision intervention approaches using Spirulina against malnutrition., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background & Aims: To determine the characteristics of adults who survived early life malnutrition (ELM) and the possible associated factors. The setting is an impoverished community in Kenya. The coastal region of Kenya has a high prevalence of acute protein-energy-malnutrition and stunting., Methods: Observational cross-sectional survey where 872 skeletally mature adults of African origin, were surveyed in a period of three months. A discrimination tool to detect ELM survivors was created. Personal, historical and family data were collected in a semi-structured questionnaire. Various observations and body measurements were done. The subjects were grouped into two, those with ELM (Group1), and those without (Group2)., Results: Group1 had 242 participants, 49.8% males, mean age of 49.1 ± 8.7 years. Group2 had 630 participants, 48.3% males, mean age 41.0 ± 9.7 years. The phenotypic characteristics included height, BMI, and head circumference (P < 0.05). Developmental characteristics were duration of schooling, occupation and income (P < 0.001). Factors associated with malnutrition were County of origin, parental education, parental occupation, and family size (P < 0.001)., Conclusions: There are discernible phenotypic and developmental characteristics associated with adult survivors of ELM. The predisposing factors for ELM are location of birth, parental education and occupation, and family size., Competing Interests: Conflict of interest The authors whose names are listed in the title page certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Parenteral nutrition (PN)-dependent adults and elderly individuals who are admitted to hospital treatment are potentially susceptible to mineral disorder complications due to depleted physiological reserves, loss of lean body mass, and increased fat mass, thus worsening inflammation., Aim: The purpose of this study is to evaluate the prevalence of hypophosphatemia, hypokalemia, and hypomagnesaemia prior and within the first 7 days of PN infusion. Furthermore, whether malnutrition and old age are associated with these disorders was also investigated., Methods: This study included a historical cohort of adult patients, and 1,040 patients whose information was prospectively entered in the database were evaluated., Results: Of the 781 patients, 27.3% were ≥65 years, 80.9% had undergone surgical treatment, 74.3% were in the intensive care unit, and 17.9% died during the hospitalization period. About 17.1% patients were malnourished. Protein energy malnutrition (PEM) was observed in 31.9% of the elderly patients and 27.1% of adults in general. Hypophosphatemia, hypokalemia, and hypomagnesemia were more prevalent before the start of PN infusion (D0: 214 [18.4%]), and new events were more common during the first 2 days of PN infusion (D1: 283 [23.1%]; D2: 243 [20.1%]. Elderly patients were more susceptible to developing hypophosphatemia (odds ratio [OR]: 1.69; 95% confidence interval [CI]: 1.29-2.19; p<0.001). Patients with PEM were also more susceptible to hypophosphatemia (OR: 3.75; 95% CI: 1.13-12.47; p=0.036)., Conclusion: Hypophosphatemia, hypokalemia, and hypomagnesemia were frequently observed in hospitalized adults and elderly patients before and particularly during the first 2 days of PN infusion. Elderly patients and patients with PEM are more susceptible to developing hypophosphatemia., Competing Interests: None

Tissues that require a great supply of nutrients and possess high metabolic demands, such as lympho-hemopoietics tissues, are the first to be affected by protein malnutrition (PM). Thus, PM directly affects hemopoiesis and the production and function of immune cells. Consequently, malnourished individuals are more susceptible to infections. Mesenchymal stem cells (MSCs) have immunomodulatory properties and are important in the formation of lympho-hemopoietic stroma. Since an adequate supply of nutrients is essential to sustain stroma formation, which is mainly constituted of MSCs and differentiated cells originated from them, this study investigated whether PM would influence some biological and immunomodulatory aspects of MSCs. Two-month-old Balb/c mice were divided into control and malnourished groups receiving normoproteic or hypoproteic diets, respectively (12% and 2% of protein) for 28 days. MSCs obtained from control (MSCct) and malnourished (MSCmaln) animals were characterized. In addition, the proliferation rate and cell cycle protein expression were determined, but no differences in these parameters were observed. In order to evaluate whether PM affects the immunomodulatory properties of MSCs, the expression of NFκB and STAT-3, and the production of IL-1α, IL-1β, IL-6, IL-10, TGF-β and TNF-α by MSCs were assessed. MSCmaln expressed lower levels of NF-κB and the production of IL-1β, IL-6 and TGF-β was significantly influenced by PM. Furthermore, MSCct and MSCmaln culture supernatants affected lymphocyte and macrophage proliferation. However, MSCmaln did not reduce the production of IFN-γ nor stimulate the production of IL-10 in lymphocytes in the same manner as observed in MSCct. Overall, this study implied that PM modifies immunosuppressive properties of MSCs., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

This study investigated the effects of pre- and postnatal conditions of protein deficiency followed to nutritional rehabilitation in the morphology of skeletal muscle. Twelve Wistar male rats were distributed in two groups: nourished (N), with normal protein diet and undernourished (U), with low protein diet. The respective diet was maintained until animals completed 21 days of life. After that, part of group U (n = 4) received normal protein diet, forming a third group, renourished group (R). Forty-two-day-old animals were euthanized and we performed histopathological and morphometric analysis of the soleus muscle. Analysis stained in hematoxylin and eosin (H&E) of the group N revealed polygonal and equidistant muscle fibers, with normal distribution in muscle fascicles. However, D group had rounded and disorganized fibers with different distances between them in muscle fascicles. R group presented muscle fibers with several formats, polygonal and rounded, and some muscle fascicles starting the reorganization process. In N group, analysis of the connective tissue showed predominance of type I collagen and a lower amount collagen type III, both well organized. Whereas U group had a predominance of disorganized type III collagen, in R group, there was return of type I collagen, but partially organized. Muscle fiber area of U (163.18 ± 52.55 μm 2 ) and R (381.79 ± 26.62 μm 2 ) groups was smaller than N (1229.2 μm 2 ± 61.12 μm 2 ). Muscle fibers density of groups U (3369 ± 1226 fibers/mm 2 ) and R (1979 ± 28 fibers/mm 2 ) was larger than N (830 ± 113 fibers/mm 2 ). The nutritional rehabilitation in the present study showed an attempt of reorganization of the muscle tissue.

Pancreatic beta cell (β) dysfunction is an outcome of malnutrition. We assessed the role of the amplifying pathway (AMP PATH) in β cells in malnourished obese mice. C57Bl-6 mice were fed a control (C) or a low-protein diet (R). The groups were then fed a high-fat diet (CH and RH). AMP PATH contribution to insulin secretion was assessed upon incubating islets with diazoxide and KCl. CH and RH displayed increased glucose intolerance, insulin resistance and glucose-stimulated insulin secretion. Only RH showed a higher contribution of the AMP PATH. The mitochondrial membrane potential of RH was decreased, and ATP flux was unaltered. In RH islets, glutamate dehydrogenase (GDH) protein content and activity increased, and the AMP PATH contribution was reestablished when GDH was blunted. Thus, protein malnutrition induces mitochondrial dysfunction in β cells, leading to an increased contribution of the AMP PATH to insulin secretion through the enhancement of GDH content and activity.

Peroxisomes are metabolic organelles necessary for anabolic and catabolic lipid reactions whose numbers are highly dynamic based on the metabolic need of the cells. One mechanism to regulate peroxisome numbers is through an autophagic process called pexophagy. In mammalian cells, ubiquitination of peroxisomal membrane proteins signals pexophagy; however, the E3 ligase responsible for mediating ubiquitination is not known. Here, we report that the peroxisomal E3 ubiquitin ligase peroxin 2 (PEX2) is the causative agent for mammalian pexophagy. Expression of PEX2 leads to gross ubiquitination of peroxisomes and degradation of peroxisomes in an NBR1-dependent autophagic process. We identify PEX5 and PMP70 as substrates of PEX2 that are ubiquitinated during amino acid starvation. We also find that PEX2 expression is up-regulated during both amino acid starvation and rapamycin treatment, suggesting that the mTORC1 pathway regulates pexophagy by regulating PEX2 expression levels. Finally, we validate our findings in vivo using an animal model., (© 2016 Sargent et al.)

Inflammatory incompetence is characteristic of acute pediatric protein-energy malnutrition, but its underlying mechanisms remain obscure. Perhaps substantially because the research front lacks the driving force of a scholarly unifying hypothesis, it is adrift and research activity is declining. A body of animal-based research points to a unifying paradigm, the Tolerance Model, with some potential to offer coherence and a mechanistic impetus to the field. However, reasonable skepticism prevails regarding the relevance of animal models of acute pediatric malnutrition; consequently, the fundamental contributions of the animal-based component of this research front are largely overlooked. Design-related modifications to improve the relevance of animal modeling in this research front include, most notably, prioritizing essential features of pediatric malnutrition pathology rather than dietary minutiae specific to infants and children, selecting windows of experimental animal development that correspond to targeted stages of pediatric immunological ontogeny, and controlling for ontogeny-related confounders. In addition, important opportunities are presented by newer tools including the immunologically humanized mouse and outbred stocks exhibiting a magnitude of genetic heterogeneity comparable to that of human populations. Sound animal modeling is within our grasp to stimulate and support a mechanistic research front relevant to the immunological problems that accompany acute pediatric malnutrition.

The aim of this study was to evaluate the effects of the protein-calorie malnutrition in BALB/c isogenic mice infected with Lacazia loboi, employing nutritional and histopathological parameters. Four groups were composed: G1: inoculated with restricted diet, G2: not inoculated with restricted diet, G3: inoculated with regular diet, G4: not inoculated with regular diet. Once malnutrition had been imposed, the animals were inoculated intradermally in the footpad and after four months, were sacrificed for the excision of the footpad, liver and spleen. The infection did not exert great influence on the body weight of the mice. The weight of the liver and spleen showed reduction in the undernourished groups when compared to the nourished groups. The macroscopic lesions, viability index and total number of fungi found in the footpads of the infected mice were increased in G3 when compared to G1. Regarding the histopathological analysis of the footpad, a global cellularity increase in the composition of the granuloma was observed in G3 when compared to G1, with large numbers of macrophages and multinucleated giant cells, discrete numbers of lymphocytes were present in G3 and an increase was observed in G1. The results suggest that there is considerable interaction between Jorge Lobo's disease and nutrition.

Background: Undernutrition contributes to 45% of all deaths in children <5 y of age worldwide, with a large proportion of those deaths caused by diarrhea. However, no validated tools exist for assessing undernutrition in children with diarrhea and possible dehydration., Objective: This study assessed the validity of different measures of undernutrition in children with diarrhea., Methods: A prospective cohort study was conducted at an urban hospital in Bangladesh. Children <60 mo of age presenting to the hospital rehydration unit with acute diarrhea were eligible for enrollment. Study staff randomly selected 1196 children for screening, of which 1025 were eligible, 850 were enrolled, and 721 had complete data for analysis. Anthropometric measurements, including weight-for-age z score (WAZ), weight-for-length z score (WLZ), midupper arm circumference (MUAC), and midupper arm circumference z score (MUACZ), were calculated pre- and posthydration in all patients. Measurements were evaluated for their ability to correctly identify undernutrition in children with varying degrees of dehydration., Results: Of the 721 patients with full data for analysis, the median percent dehydration was 4%. Of the 4 measures evaluated, MUAC and MUACZ demonstrated 92-94% agreement pre- and posthydration compared with 69-76% for WAZ and WLZ. Although each 1% change in hydration status was found to change weight-for-age by 0.0895 z scores and weight-for-length by 0.1304 z scores, MUAC and MUACZ were not significantly affected by dehydration status. Weight-based measures misclassified 12% of children with severe underweight and 14% with severe acute malnutrition (SAM) compared with only 1-2% for MUAC and MUACZ., Conclusions: MUAC and MUACZ were the most accurate predictors of undernutrition in children with diarrhea. WAZ and WLZ were significantly affected by dehydration status, leading to the misdiagnosis of many patients on arrival with severe underweight and SAM. This trial was registered at clinicaltrials.gov as NCT02007733., (© 2015 American Society for Nutrition.)

Background: Protein-energy malnutrition (PEM) can lead to growth hormone (GH) resistance. Leucine supplementation diets have been shown to increase protein synthesis in muscles. Our study aimed at investigating if long-term leucine supplementation could modulate GH-insulin-like growth factor (IGF)-1 system function and mammalian target of rapamycin (mTOR)-related signal transduction in skeletal muscles in a rat model of severe malnutrition., Methodology/principal Findings: Male Sprague-Dawley rats (n = 50; weight, 302 ± 5 g) were divided into 5 treatment groups, including 2 control groups (a normal control group that was fed chow and ad libitum water [CON, n = 10] and a malnourished control group [MC, n = 10] that was fed a 50% chow diet). After undergoing a weight loss stage for 4 weeks, rats received either the chow diet (MC-CON, n = 10), the chow diet supplemented with low-dose leucine (MC-L, n = 10), or the chow diet supplemented with high-dose leucine (MC-H, n = 10) for 2 weeks. The muscle masses of the gastrocnemius, soleus, and extensor digitorum longus were significantly reduced in the MC group. Re-feeding increased muscle mass, especially in the MC-L and MC-H groups. In the MC group, serum IGF-1, IGF-binding protein (IGFBP)-3, and hepatic growth hormone receptor (GHR) levels were significantly decreased and phosphorylation of the downstream anabolic signaling effectors protein kinase B (Akt), mTOR, and ribosomal protein S6 kinase 1 (S6K1) were significantly lower than in other groups. However, serum IGF-1 and IGF binding protein (IGFBP)-3 concentrations and hepatic growth hormone receptor (GHR) levels were significantly higher in the MC-L and MC-H groups than in the MC-CON group, and serum IGFBP-1 levels was significantly reduced in the MC-L and MC-H groups. These changes were consistent with those observed for hepatic mRNA expression levels. Phosphorylation of the downstream anabolic signaling effectors Akt, mTOR, and S6K1 were also significantly higher in the MC-L and MC-H groups than in the MC-CON group., Conclusion/significance: Our data are the first to demonstrate that long-term supplementation with leucine improved acquired growth hormone resistance in rats with protein-energy malnutrition. Leucine might promote skeletal muscle protein synthesis by regulating downstream anabolic signaling transduction.

Objective: Nutritional status is a powerful predictor of survival in maintenance hemodialysis patients but remains challenging to assess. We defined a new Protein Energy Wasting (PEW) score based on the nomenclature proposed by the International Society of Renal Nutrition and Metabolism in 2008., Design and Methods: This score, graded from 0 (worse) to 4 (best) was derived from 4 body nutrition compartments: serum albumin, body mass index, a normalized serum creatinine value, and protein intake as assessed by nPNA., Subjects: We applied this score to 1443 patients from the ARNOS prospective dialysis cohort and provide survival data from 2005 until 2008., Main Outcome Measure: Patients survival at 3.5 year., Results: Survival ranged from 84%-69% according to the protein-energy wasting score. There was a clear-cut reduction in survival (5%-7%; P < 0.01) for each unit decrement in the score grade. There was a 99% survival at 1 year for patients with the score of 4. In addition, the 6-month variation of this PEW score also strongly predicted patients' survival (P < 0.01)., Conclusion: A new simple and easy-to-get PEW score predicts survival in maintenance hemodialysis patients. Furthermore, increase of this nutritional score over time also indicates survival improvement, and may help to better identify subgroups of patients with a high mortality rate, in which nutrition support should be enforced., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background/objectives: Protein malnutrition (PM) is a worldwide problem affecting brain development in a large number of children. The present study was aimed at studying the perturbations in antioxidant defense system resulting from protein deficiency and to evaluate the preventive effect of Se and Zn on cortex and cerebellum., Methods: Well-fed (WF) and PM rats were fed on 16 and 5% protein diet, respectively. After 10 weeks, animals were supplemented with Se and Zn at a concentration of 0.15 and 227 mg/l in drinking water for 3 weeks., Results: PM rats showed significant increase in lipid peroxidation, nitrite, and protein carbonyl levels. Reduction in the activity of antioxidant enzymes, thiol levels, GSH/GSSG ratio, and neurobehavioral deficits were observed in PM groups. Se and Zn supplementation reduced the levels of lipid peroxidation, nitrite, and protein carbonyl and restored the activity of antioxidant enzymes and thiol levels in the cortex and cerebellum of PM rats along with neurobehavioral deficits., Discussion: The study showed that Se and Zn supplementation might be beneficial in preventing biochemical alterations and neurobehavioral deficits in PM children.

This study sought to morphometrically analyze the jejunal wall of protein-malnourished rats administered a probiotic supplement. The sample consisted of recently weaned Wistar rats (Rattus norvegicus) distributed among four groups: animals given a commercial diet (G1, n = 4); animals given the same ration as G1 plus a probiotic supplement (G2, n = 4); animals given a 4% protein diet (G3, n = 4); and animals given the same ration as G3 plus a probiotic supplement (G4, n = 4). After 12 weeks, part of the jejunum was harvested and subjected to routine histological processing. Transverse sections with a thickness of 3 µm were stained with HE, and histochemical techniques were used to assay for glycoconjugates, including staining with periodic acid-Schiff (PAS) + diastase, Alcian Blue (AB) solution at pH 2.5, and Alcian Blue solution at pH 1.0. Morphometric analysis of the bowel wall showed that the probiotic culture used in this study induced hypertrophy of several layers of the jejunal wall in well-nourished animals and reduced the bowel wall atrophy usually observed in protein-malnourished animals. Neither malnutrition nor the use of probiotics altered the relationship between the number of goblet cells and the number of enterocytes.

Purpose: The pathway linking late-life malnutrition to greater risk of cardiovascular disease is unclear. Microcirulatory changes assessed by retinal vascular caliber have been linked with increased risk of stroke and coronary heart disease. The purpose of this study was to examine whether retinal vascular calibers are associated with malnutrition in elderly subjects free of cardiovascular diseases., Methods: This was a cross-sectional analysis of a community-dwelling cohort comprising 1145 individuals aged 60 years and older. Retinal vascular caliber was measured from fundus photographs using a semiautomated, standardized imaging software. Malnutrition was assessed using body mass index (BMI) < 18.5 kg/m(2) and biomarkers of protein malnutrition: plasma albumin and transthyretin., Results: In a multivariate model controlling for cardiovascular risk factors, retinal venular caliber was related to BMI (P = 0.0002) with an increased mean caliber for individuals with obesity and for those with low BMI. After multivariate adjustment for age, sex, hypertension, smoking, high-density lipoprotein (HDL) cholesterol, glomerular filtration rate and BMI, lower levels of albumin or transthyretin were associated with larger retinal venular caliber (P = 0.026 and P = 0.0018, respectively), that remain significant when adjusting for CRP (P = 0.040 and P = 0.0060, respectively) or orosomucoid (P = 0.034 and P = 0.0020, respectively). The relationships between retinal arteriolar caliber and BMI, albumin and transthyretin did not reach significance (P = 0.14, P = 0.12, and P = 0.15, respectively)., Conclusions: Protein malnutrition was identified as an additional factor associated with retinal venular dilatation beyond inflammation. This suggests that early microvascular changes may be one of the underlying mechanisms of increased risk of cardiovascular disease observed in elderly subjects suffering from malnutrition., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Purpose of Review: Currently, feeding the ICU patient is highly discussed. Energy feeding has been the topic of randomized studies, but protein feeding has not. Study results are contradictory on early feeding; however, little is known about early protein requirement. What is this protein requirement based on, therefore what are the fundamental determinants?, Recent Findings: Recent studies have addressed the importance of protein feeding and/or muscle (protein) wasting in critically ill patients. Targeted feeding has been shown to improve protein balance in one study, and infection rate in one study. Low muscle mass that is already present during ICU admission has been shown to be related to higher mortality, in two studies. Four studies have related muscle wasting to (protein) feeding strategies with very diverse results: Two small studies have reported no advantage [n = 15, computed tomography] or negative impact (n = 62, ultrasound, 50% sepsis patients) of protein on muscle wasting. Two studies, one small (n = 33, computed tomography) and one very large (n = 1372, Subjective Global Assessment), have reported a positive impact of (early) feeding on muscle wasting., Summary: Fundamental to adequate protein feeding in critically ill patients, at least 1.2 g protein/kg per day, is targeted energy feeding using indirect calorimetry. The level of protein requirement is related to fat free mass or muscle mass, which makes sex and BMI also relevant. Targeted early protein feeding is found to improve short-term outcome, reduction of muscle wasting and hospital mortality. Long-term outcome of protein feeding has not been studied. However, targeted protein feeding may be harmful in sepsis patients. Up to now, we lack biomarkers that provide caregivers with an instrument to increase protein feeding up to the individual protein requirement of the critically ill patient.

Aim: To investigate the effect of protein-energy malnutrition on intestinal barrier function during rotavirus enteritis in a piglet model., Methods: Newborn piglets were allotted at day 4 of age to the following treatments: (1) full-strength formula (FSF)/noninfected; (2) FSF/rotavirus infected; (3) half-strength formula (HSF)/noninfected; or (4) HSF/rotavirus infected. After one day of adjustment to the feeding rates, pigs were infected with rotavirus and acute effects on growth and diarrhea were monitored for 3 d and jejunal samples were collected for Ussing-chamber analyses., Results: Piglets that were malnourished or infected had lower body weights on days 2 and 3 post-infection (P < 0.05). Three days post-infection, marked diarrhea and weight loss were accompanied by sharp reductions in villus height (59%) and lactase activity (91%) and increased crypt depth (21%) in infected compared with non-infected pigs (P < 0.05). Malnutrition also increased crypt depth (21%) compared to full-fed piglets. Villus:crypt ratio was reduced (67%) with viral infection. There was a trend for reduction in transepithelial electrical resistance with rotavirus infection and malnutrition (P = 0.1). (3)H-mannitol flux was significantly increased (50%; P < 0.001) in rotavirus-infected piglets compared to non-infected piglets, but there was no effect of nutritional status. Furthermore, rotavirus infection reduced localization of the tight junction protein, occludin, in the cell membrane and increased localization in the cytosol., Conclusion: Overall, malnutrition had no additive effects to rotavirus infection on intestinal barrier function at day 3 post-infection in a neonatal piglet model.

This study investigated the effect of protein malnutrition on metabolism and toxicity of cisplatin (CP), 5-fluorouracil (FU) and mitomycin C (MMC) in rat stomach. Weanling male Wistar rats received a normal (24%) or low (2.5%) protein diet for 28 days and were allocated into: normally-fed control, protein-malnourished control (PM), 3 normally-fed drug-treated groups and 3 protein-malnourished drug-treated groups (PM-CP, PM-FU and PM-MMC). Cisplatin and MMC were injected intraperitoneally (8 mg/kg on day 26 and 1 mg/kg/day for 7 days, respectively). 5-Fluorouracil was given orally (50 mg/kg/day for 5 days). Compared with normally-fed counterparts, PM-CP rats exhibited higher glutathione S-transferase, aminopeptidase N and cysteine S-conjugate beta-lyase (CCBL) and lower gamma-glutamyltransferase activities, PM-FU rats exhibited decreased dihydropyrimidine dehydrogenase and cytochrome P450 1A1/2 activities and PM-MMC rats showed higher quinone reductase and depleted xanthine oxidase activities. Protein-malnourished drug-treated groups exhibited exacerbated gastrotoxicity, relative to normally-fed counterparts, manifested by lower mucus levels, higher permeability and histopathological deterioration, along with increased oxidative stress in PM-CP rats and exaggerated prostaglandin E2 production in PM-MMC rats. Conclusively, protein malnutrition alters CP, FU and MMC metabolism in rat stomach by enhancing CCBL pathway for CP activation, delaying FU elimination and activating two-electron reduction of MMC, potentiating their gastrotoxicity., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: Early malnutrition is a highly prevalent condition in developing countries. Different rodent models of postnatal early malnutrition have been used to approach the subject experimentally, inducing early malnutrition by maternal malnutrition, temporal maternal separation, manipulation of litter size or the surgical nipple ligation to impair lactation. Studies on the behaviour of (previously) malnourished animals using animal models have produced sometimes contradictory results regarding the effects of early postnatal malnutrition and have been criticized for introducing potential confounding factors. The present paper is a first report on the behavioural effects of early malnutrition induced by an alternative approach: mice nursed by α-casein-deficient knockout dams showed a severe growth delay during early development and substantial catch-up growth after weaning when compared with animals nursed by wild-type females., Methods: Established behavioural tests were used to study the consequences of early postnatal malnutrition on mouse pups at weaning and after partial weight recovery., Results: Despite the impaired growth, the only behavioural difference between malnourished and normally growing animals was found in exploratory behaviour during acute malnutrition at the time of weaning. After partial catch-up in weight early protein malnourished animals showed no indication of lasting effects on general activity, emotionality and exploration, memory, and pain reactivity., Discussion: These results suggest that the role of early nutrition on behavioural development after recovery in animal models may have been overestimated. Further careful examination of this animal model in terms of maternal care and offspring behaviour will be necessary to confirm if mice nursed by α-casein-deficient dams offer an alternative to existing models while eliminating potential confounding factors.

The objective of this study was to compare the effects of the tactile/handling stimulation (H) and environmental enrichment (EE) in well-nourished (C - 16% of protein) and malnourished (M - 6% of protein) rats tested in the elevated plus-maze (EPM) at 36 and 37 days of age. The results showed higher exploration of the open arms in the EPM in M as compared with C animals, as well as lower index of risk assessment behaviors, and EE, but not H, reversed the alterations produced by malnutrition in the EPM. Biochemical analysis showed higher levels of corticosterone in M when compared with C rats. The non-stimulated animals presented higher levels of polyamines in the hippocampus when compared with the stimulated ones in both diet conditions. It is suggested that both the lower anxiety levels and the lower risk-assessment behaviors in the EPM, as well as the higher levels of corticosterone, can be due to alterations in the activity of the hypothalamic-pituitary-adrenal axis as the result of early protein malnutrition.

Giardiasis is one of the most common parasitic diseases worldwide, and the disease is an important cause of diarrhoea and malabsorption in children and immunosuppressed individuals. However, there is no evidence that characterises malnutrition as an aggravating factor for this disease. We evaluated changes in villi structures to examine the association between malnutrition and Giardia lamblia infection. We used 32 gerbils, divided into 4 groups: Control (CT) and Control Infected (CTIn), which each received a 20% protein diet, Malnourished (MN) and Malnourished Infected (MNIn), which each received a 5% protein diet. Groups CTIn and MNIn were inoculated with 1×10(6) trophozoites of G. lamblia, while the remaining groups were mock infected. Seven days post-infection, all groups were sacrificed, and the proximal portions of the small intestines were collected for the analysis of villus height, mucus area and extent of Giardia infection. Gerbils fed with a low-protein diet had significantly lower body weights. Malnourished infected animals presented significantly increased production of mucus, suggesting a synergism occurs between malnutrition and Giardiasis, potentially to control the adhesion of Giardia in the mucosa. Villus height was significantly lower in group MNIn compared to CTIn. This work suggests that malnutrition contributes to severity of Giardiasis by decreasing the intestinal absorption capacity via shortening of the villi., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The aim of this project was to study the effects of protein malnutrition in the anterior commissure of male albino Wistar rats, submitted to diets with different levels of protein to evaluate the possible morphological and developmental changes of the myelinated nervous fibers and glial cells of this important neural structure during the postnatal period until 120 days of age. In this study the animals (dams and pups) were divided into three groups: the control group which received a commercial diet from the laboratory (22% protein); the nourished group which received a diet of 16% of protein (casein); and the malnourished group which received a diet of 6% of protein (casein). Rat pups were fed by lactating females during the lactation period. After weaning the pups received the same diet until 120 days of age. The results obtained showed that the malnourished animals presented less body and brain growth and important morphological changes in the anterior commissure such as the retard in the myelination, damaged myelinic nervous fibers, and the increase of the interstitial space characterizing edema and vacuolization. The current study shows that the effects of protein malnutrition in the anterior commissure cause a bigger alteration in the posterior limb of the referred commissure, indicating that it is more vulnerable to malnutrition and more susceptible to damages of the anterior limb.

Protein malnutrition (PM) results in pathological changes that are associated with peripheral leukopenia, bone marrow (BM) hypoplasia and alterations in the BM microenvironment leading to hematopoietic failure; however, the mechanisms involved are poorly understood. In this context, the BM mesenchymal stem cells (MSCs) are cells intimately related to the formation of the BM microenvironment, and their differentiation into adipocytes is important because adipocytes are cells that have the capability to negatively modulate hematopoiesis. Two-month-old male Balb/c mice were subjected to protein-energy malnutrition with a low-protein diet containing 2% protein, whereas control animals were fed a diet containing 12% protein. The hematopoietic parameters and the expression of CD45 and CD117 positive cells in the BM were evaluated. MSCs were isolated from BM, and their capability to produce SCF, IL-3, G-CSF and GM-CSF were analyzed. The expression of PPAR-γ and C/EBP-α as well as the expression of PPAR-γ and SREBP mRNAs were evaluated in MSCs together with their capability to differentiate into adipocytes in vitro. The malnourished animals had anemia and leukopenia as well as spleen and bone marrow hypoplasia and a reduction in the expression of CD45 and CD117 positive cells from BM. The MSCs of the malnourished mice presented an increased capability to produce SCF and reduced production of G-CSF and GM-CSF. The MSCs from the malnourished animals showed increased expression of PPAR-γ protein and PPAR-γ mRNA associated with an increased capability to differentiate into adipocytes. The alterations found in the malnourished animals allowed us to conclude that malnutrition committed MSC differentiation leading to adipocyte decision and compromised their capacity for cytokine production, contributing to an impaired hematopoietic microenvironment and inducing the bone marrow failure commonly observed in protein malnutrition states.

Research objective was studying of features of functional diseases of digestive organs at patients with a dysplasia of a connecting tissue. In the conditions of the specialized Center of a dysplasia of a connecting tissue the assessment of a functional condition of digestive organs at 121 patients with signs of a dysplasia of a connecting tissue is carried out. High frequency of functional disorders of digestive organs at patients with a dysplasia of a connecting tissue (74-75%) is registered. Overlapping of syndromes of functional diseases (functional dyspepsia and syndrome of the angry intestine) it is registered at 73 +/- 3.9% of patients with DST, in group of comparison - at 9 +/- 2.3% (p &It; 0.001). Syndromes demonstrated against a wide range of changes of the digestive organs associated with a dysplasia of a connecting tissue. Existence of a dysplasia of a connecting tissue defines variety and features of a course of functional diseases of digestive organs, development of a syndrome of a maldigestiya and advance of an protein-energy malnutrition at this category of patients.

Maternal protein restriction plays a critical role in the developmental programming of later disease susceptibility of the fetus. Developmental insults could exert permanent effects on health through alteration of tissue morphology. As the liver has the greatest number of functions among other body organs, this study aimed at evaluating the effects of maternal dietary protein insufficiency on the structure and the proliferative capacity of the liver in rat fetuses. Morphometric histological studies and biochemical analysis were performed. Twenty adult Albino female Wistar rats were divided into two groups after confirmation of pregnancy. Group I (ST), serving as control, was fed a standard diet (20% protein) and group II (LP) a low protein diet (5% protein). Fetuses were extracted on the day 21.5 of pregnancy. Group II morphometric results revealed a significant decrease in the mothers' weight gain, number and weight of fetuses and weight of fetal livers, but there was also an increase in the mean area of hepatocytes. Histological results showed apoptosis, vacuolization of the hepatocytes, increased positivity of the Oil Red O stained fat droplets and the PAS-positive stained glycogen granules. Liver TUNEL showed increased apoptotic nuclei. Ki-67 immunostaining showed decreased proliferation of the hepatocytes. Ultrastructurally, the nucleus showed peripheral masses of heterochromatin besides irregular nuclear and cell membranes. Mitochondria varied in shape with loss of cristea. Biochemically, there was a significant decrease in the protein concentration and a significant increase in the glycogen concentration in livers of group II. It thus appears that the maternal metabolic condition not only reduced fetal growth in response to protein restriction, but also altered the structure of the liver., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

In the conditions of the specialized Center of a dysplasia of a connecting tissue the assessment of an protein--energy malnutrition at 121 patients with signs of a dysplasia of a connecting tissue is carried out. High frequency of an oligotrophy at patients with a dysplasia of a connecting tissue is registered. The I degree of a gipotorofiya is taped at 26.21% of the patients, II degree--at 18.44%, the III degree--at 3.88% of patients.

The effects of severe protein malnutrition (4%) on myenteric neurons of Wistar rat duodenum, in relation to a standard 22%-protein diet for rodents, were assessed in this study. Segments of the duodenum from 10 rats from each nutritional group were submitted to the elaboration of whole mounts - 5 stained with Giemsa to determine the total population of myenteric neurons and the others stained by a histochemical method to detect nervous cells through the NADPH-diaphorase enzyme activity for studying the subpopulation of nitrergic neurons. The area of 100 neurons per animal, totalizing 2,000 neurons, were randomly measured by using the Image Pro-Plus(®)software. Malnourished rats presented 34.38% lower body weight and 10.60% duodenum length reduction when compared to the control group. Quantitative analysis demonstrated no significant differences between control and malnourished group by using Giemsa; however, as the organ reduction was not followed by an increase inversely proportional to the density of neurons, the condition imposed suggests the loss of neurons from the total population. Nevertheless, through NADPH-d histochemistry, there was a neuronal density increase for the malnourished group. There was no significant difference between the groups for both techniques with respect to the morphometric analysis of the body cell.

Chronic malnutrition leads to multiple changes in β-cell function and peripheral insulin actions to adapt glucose homeostasis to these restricted conditions. However, despite glucose homeostasis also depends on glucagon effects, the role of α-cells in malnutrition is largely unknown. Here, we studied α-cell function and hepatic glucagon signaling in mice fed with low-protein (LP) or normal-protein diet for 8 wk after weaning. Using confocal microscopy, we found that inhibition of Ca²⁺ signaling by glucose was impaired in α-cells of LP mice. Consistent with these findings, the ability of glucose to inhibit glucagon release in isolated islets was also diminished in LP mice. This altered secretion was not related with changes in either glucagon gene expression or glucagon content. A morphometric analysis showed that α-cell mass was significantly increased in malnourished animals, aspect that was probably related with their enhanced plasma glucagon levels. When we analyzed the hepatic function, we observed that the phosphorylation of protein kinase A and cAMP response-binding element protein in response to fasting or exogenous glucagon was impaired in LP mice. Additionally, the up-regulated gene expression in response to fasting observed in the hepatic glucagon receptor as well as several key hepatic enzymes, such as peroxisome proliferator-activated receptor γ, glucose-6-phosphatase, and phosphoenolpyruvate carboxykinase, was altered in malnourished animals. Finally, liver glycogen mobilization in response to fasting and the ability of exogenous glucagon to raise plasma glucose levels were lower in LP mice. Therefore, chronic protein malnutrition leads to several alterations in both the α-cell function and hepatic glucagon signaling.

The purpose of this study was to evaluate the effect of protein malnutrition on the skin epidermis of mice. A low protein diet induced thinning of the skin epidermis, a decrease of cell proliferative activity in epidermal cells and a decrease of stratum corneum hydration. Dityrosine was immunostained in the cytoplasm of epidermal cells in the low protein diet group. Plasma advanced oxidation protein product (AOPP) levels were significantly more increased in the low protein diet group than in the control diet group. These results suggest that protein malnutrition adversely affects the structure and water barrier and reservoir functions of the skin epidermis, and these pathological changes are associated with the expressions of protein oxidation markers, dityrosine and AOPP.

Protein-energy malnutrition (PEM) affects ~16% of patients at admission for stroke. We previously modeled this in a gerbil global cerebral ischemia model and found that PEM impairs functional outcome and influences mechanisms of ischemic brain injury and recovery. Since this model is no longer reliable, we investigated the utility of the rat 2-vessel occlusion (2-VO) with hypotension model of global ischemia for further study of this clinical problem. Male, Sprague-Dawley rats were exposed to either control diet (18% protein) or PEM induced by feeding a low protein diet (2% protein) for 7d prior to either global ischemia or sham surgery. PEM did not significantly alter the hippocampal CA1 neuron death (p = 0.195 by 2-factor ANOVA) or the increase in dendritic injury caused by exposure to global ischemia. Unexpectedly, however, a strong trend was evident for PEM to decrease the consistency of hippocampal damage, as shown by an increased incidence of unilateral or no hippocampal damage (p=0.069 by chi-square analysis). Although PEM caused significant changes to baseline arterial blood pH, pO(2), pCO(2), and fasting glucose (p<0.05), none of these variables (nor hematocrit) correlated significantly with CA1 cell counts in the malnourished group exposed to 2-VO (p>0.269). Intra-ischemic tympanic temperature and blood pressure were strictly and equally controlled between ischemic groups. We conclude that co-existing PEM confounded the consistency of hippocampal injury in the 2-VO model. Although the mechanisms responsible were not identified, this model of brain ischemia should not be used for studying this co-morbidity factor., (© 2011 Bentham Science Publishers Ltd.)

Previously it has been demonstrated that protein-energy malnutrition (PEM) impairs habituation in the open field test following global ischemia. The present study examined the hypothesis that PEM exerts some of its deleterious effects on functional outcome by altering the post-ischemic expression of the plasticity-associated genes brain-derived neurotrophic factor (BDNF), its receptor tropomyosin-related kinase B (trkB), and growth-associated protein-43 (GAP-43). Male, Mongolian gerbils (11-12 wk) were randomized to either control diet (12.5% protein) or PEM (2% protein) for 4 wk, and then underwent 5 min bilateral common carotid artery occlusion or sham surgery. Tympanic temperature was maintained at 36.5 ± 0.5°C during surgery. Brains collected at 1, 3 and 7 d post-surgery were processed by in-situ hybridization or immunofluorescence. BDNF and trkB mRNA expression was increased in hippocampal CA1 neurons after ischemia at all time points and was not significantly influenced by diet. However, increased trkB protein expression after ischemia was exacerbated by PEM at 7 d in the CA1 region. Post-ischemic GAP-43 protein increased at 3 and 7 d in the CA1 region, and PEM intensified this response and extended it to the CA3 and hilar regions. PEM exerted these effects without exacerbating CA1 neuron loss caused by global ischemia. The findings suggest that PEM increases the stress response and/or hyper-excitability in the hippocampus after global ischemia. Nutritional care appears to have robust effects on plasticity mechanisms important to recovery after brain ischemia.

The mechanism by which protein malnutrition impairs glucose-stimulated insulin secretion in the pancreatic beta-cell is not completely known but may be related to alterations in the signaling events involved in insulin release. Here, we aimed to study the stimulus-secretion coupling of beta-cells from mice fed with low-protein (LP) diet or normal-protein (NP) diet for 8 wk after weaning. Patch-clamp measurements in isolated cells showed that beta-cells from LP mice had a resting membrane potential that was more hyperpolarized than controls. Additionally, depolarization and generation of action potentials in response to stimulatory glucose concentrations were also impaired in beta-cells of LP mice. All these alterations in the LP group were most likely attributed to higher ATP-dependent K(+) (K(ATP)) channel activity in resting conditions and lower efficiency of glucose to induce the closure of these channels. Moreover, a Western blot analysis revealed higher protein levels of the sulphonylurea receptor of the K(ATP) channel in islets of LP mice. Because beta-cell Ca(2+) signals depend on electrical activity, intracellular Ca(2+) oscillations were measured by fluorescence microscopy in intact islets, indicating a lower response to glucose in the LP group. Finally, cell-to-cell synchrony of Ca(2+) signals was analyzed by confocal microscopy. Islets from LP mice exhibited a decreased level of coupling among beta-cells, which was probably due to the low expression levels of connexin 36. Therefore, low-protein diet leads to several alterations in the stimulus-secretion coupling of pancreatic beta-cells that might explain the diminished insulin secretion in response to glucose in this malnutrition state.

Aim and Method: Based on the systematic analyses of a 10-year period at the Institute of Forensic Medicine at the University Clinic Hamburg-Eppendorf, the frequency of underweight in elderly persons at their time of death was retrospectively calculated. Body mass index (BMI) values <20 kg/m(2) were taken as indicative of underweight and the data of 1,551 women and 2,270 men, mean age 69 years (51-101 years) were analyzed., Results: The prevalence of underweight was 15.4%. Low BMI values were more frequent in women than men (18.8 vs. 13.1%) and more frequent in persons needing professional nursing care at the time of death (28.9%). Underweight increased for the age range 70-79 from about 15% to over 38% for those 90 years and older at the time of death. Pressure sores were documented in 1.8% of cases. Persons in need of professional nursing care more often had pressure sores at their time of death. Furthermore, pressure sores were observed more often in underweight elderly in need of professional nursing care., Conclusion: Underweight at the time of death is observed more often in the very old. This is associated with the need for professional nursing care and also the occurrence of pressure sores. Less than 5% of persons with tumors were included. The results underscore the need of early detection of people at risk of malnutrition when growing older.

Background: The frequency of diagnosis of celiac disease has increased since the introduction of serologic testing. The number of patients in whom extraintestinal symptoms reflect the initial manifestation is rising. Common symptoms are changes in blood counts, which can arise from changes in all cell lineages. Among these, iron deficiency anemia is very common, but also thrombocytosis and thrombocytopenia have been reported to manifest themselves within the framework of celiac disease., Case Report: The authors report on a patient with malnutrition, macrocytic anemia, and pronounced thrombocytopenia. Based on changes of peripheral blood smear and endoscopic result, celiac disease was suspected that could be confirmed by histology of duodenal biopsies. The thrombocytopenia was reversible after initiation of gluten-free diet and folic acid substitution. In addition, clinical symptoms resolved and hematologic reconstitution could be observed., Conclusion: Similar deficiencies have almost exclusively been observed in patients with increased folic acid requirements during pregnancy or intensive care. Celiac disease must be taken into consideration, if changes in blood counts occur associated with gastrointestinal symptoms.

Background: Patients with cystic fibrosis classically present with evidence of pulmonary disease, exocrine pancreatic insufficiency, and high sweat chloride concentrations. Dermatitis as an initial manifestation of the disease is uncommon and has been attributed to multiple nutritional deficiencies., Observation: We describe the case of a 3-month-old female infant with cystic fibrosis presenting with dermatitis in the setting of protein-energy malnutrition. A review of the laboratory study results in this case and others showed that a deficiency in zinc, essential fatty acids, and protein likely contributes to the development of the rash seen in cystic fibrosis., Conclusions: Given the frequent delay in diagnosis, as well as the increased morbidity and mortality associated with protein-energy malnutrition in these patients, it is important to consider cystic fibrosis as a possible diagnosis in any infant presenting with a rash and other signs of malnutrition. The relative contribution of specific nutritional deficiencies and the degree to which they influence and interact with each other in producing the dermatitis remain unclear, although they may all affect a common underlying metabolic pathway.

The mandible has a mixed embryological origin, and its growth is associated with the secondary cartilage of the condyle process (CP). In this area, growth depends on an array of intrinsic and extrinsic factors that influence protein metabolism. In the present study, we used an adolescent rat model to evaluate the growth and development of the CP under conditions of pre- and postnatal protein deficiency, combined with or without the stress of severe burn injury (BI). We found that protein deficiency severely undermined the growth of the CP, by altering the thickness of its constituent layers. BI is also capable of affecting CP growth, although the effect is less severe than protein deficiency. Interestingly, the summed effect of protein deficiency and BI on the CP is less severe than protein deficiency alone. A possible explanation is that the increased carbohydrates in a hypoproteic diet stimulate the production of endogenous insulin and protein synthesis, which partially compensates for the loss of lean body mass caused by BI.

Nitrogenous metabolism, vitamin provision and anthroponietric indices were inventigated in 1560 Uzbek youths (18-21 years old) with diverse alimentary status. Changes cheatinine in urine, insufficient vitamines content and violations of authropometric indices were revald in patients with protein-calorie deficiency.

Objective: Guatemala is a country severely affected by malnutrition, particularly in its child population. The present study aimed to assess the impact of recognised aetiological factors on the prevalence of malnutrition and to establish the efficacy of a Guatemalan malnutrition clinic by examining the changes in the prevalence of malnutrition in the ten surrounding communities served by the clinic., Design: Records of children (n 7681) aged 5-16 years seen by the clinic between 2004 and 2006 were examined. Anthropometric data for each child were taken from these records and used as an indicator for their nutritional status to estimate the change in rates of malnutrition during this period., Results: An overall reduction was seen in all forms of malnutrition over the 3-year period, although over 50 % of the study population remained malnourished in 2006. A consistent reduction was also seen in rates of moderate and severe malnutrition, but not in rates of mild malnutrition., Conclusions: The results demonstrate that clinics such as Primeros Pasos can have a beneficial effect on schoolchildren, particularly those who are severely malnourished. A need has been highlighted for more research in this area, particularly how clinics such as Primeros Pasos can be best used in the fight against malnutrition.

A low-protein diet leads to functional and structural pancreatic islet alterations, including islet hypotrophy. Insulin-signaling pathways are involved in several adaptive responses by pancreatic islets. We determined the levels of some insulin-signaling proteins related to pancreatic islet function and growth in malnourished rats. Adult male Wistar rats (N = 20 per group) were fed a 17% protein (normal-protein diet; NP) or 6% protein (low-protein diet; LP), for 8 weeks. At the end of this period, blood glucose and serum insulin and albumin levels were measured. The morphometric parameters of the endocrine pancreas and the content of some proteins in islet lysates were determined. The beta-cell mass was significantly reduced ( congruent with 65%) in normoglycemic but hypoinsulinemic LP rats compared to NP rats. Associated with these alterations, a significant 30% reduction in insulin receptor substrate-1 and a 70% increase in insulin receptor substrate-2 protein content were observed in LP islets compared to NP islets. The phosphorylated serine-threonine protein kinase (pAkt)/Akt protein ratio was similar in LP and NP islets. The phosphorylated forkhead-O1 (pFoxO1)/FoxO1 protein ratio was decreased by 43% in LP islets compared to NP islets (P < 0.05). Finally, the ratio of phosphorylated-extracellular signal-related kinase 1/2 (pErk1/2) to total Erk1/2 protein levels was decreased by 71% in LP islets compared to NP islets (P < 0.05). Therefore, the reduced beta-cell mass observed in LP rats is associated with the reduction of phosphorylation in mitogenic-related signals, FoxO1 and Erk proteins. The cause/effect basis of this association remains to be determined.

The objectives were to determine if blood IL-10 levels rise during the early stages of acute (wasting) pre-pubescent malnutrition in metabolically distinct murine models known to depress inflammatory immune competence and whether systemic IL-10 production is affected in these pathologies. Weanling C57BL/6J mice were assigned to dietary protocols that elicited wasting pathologies mimicking the human diseases of marasmus (restricted-intake group) or incipient kwashiorkor (low-protein group). An age-matched control group also was included. Serum IL-10 bioactivities were assessed in the early (day 3) and advanced (day 14) stages of weight loss, and net systemic IL-10 production was assessed at the same stages of pathology by in vivo cytokine capture. Blood IL-10 levels were elevated in both malnourished groups relative to controls at days 3 and 14 (range of P values: 0.03-0.0001). Further, despite a limited supply of energy and nitrogenous substrates, the systemic IL-10 production rate was at least sustained in the malnourished groups and, in fact, was elevated in the marasmic group (P=0.05) throughout the progression of weight loss. IL-10 emerges as an anti-inflammatory mediator positioned to participate in initiating and upholding the depressed immune competence that accompanies acute pre-pubescent deficits of protein and energy.

The objective of this study was to investigate whether malnourished autopsied adults would present higher frequency of pneumonitis than non-malnourished ones would. All of the autopsied adults (n = 175; age > or = 18 years) with complete records, including weight and height data, were included. Pneumonitis was observed more frequently in malnourished individuals (59.1%) than in non-malnourished individuals (41.3%). This study showed that the percentage of pneumonitis among autopsied adults was high, in addition to an increased risk of pneumonitis among these individuals.

This case control study was carried out in the department of Biochemistry, Mymensingh Medical College in co-operation with the Pediatric wards of Mymensingh Medical College Hospital and Ganashasthya Nagar Hospital, Dhaka during the period from July 2005 to June 2006. The aim of the study was to explore the status of serum zinc and copper level in Bangladeshi children with Protein Energy Malnutrition (PEM) as a means to monitor the possibility of management of these children as each of these mineral deficiencies produce typical deficiency syndromes. A total of 68 children aging from five months to five years were included in this study. Subjects were divided into two groups-Group I (Control; n=20)-children with normal growth, weight for age between 3rd and 97th centile curve, Centers for Disease Control (CDC) growth chart, USA, 2000 and group II-(children with PEM; n=48)-children with retarded growth, weight for age below 3rd centile of CDC growth chart, USA, 2000. Group II was again divided into three subgroups according to Wellcome classification of PEM and clinical features. These were Group IIA: Marasmus (n=19), Group IIB: Kwashiorkor (n=14) and Group IIC: Marasmic Kwashiorkor (n=15). Serum zinc and copper levels were determined by Atomic Absorption Spectrophotometric method. Statistical analysis was done by using Statistical Package for the Social Sciences (SPSS) window package. Among the different groups of children mean+/-SD (Standard Deviation) of serum zinc in PEM (59.85+/-11.18 microg/dl), Marasmus (66.73+/-8.23 microg/dl), Kwashiorkor (49.69+/-10.35 microg/dl) and Marasmic Kwashiorkor (60.63+/-8.04 microg/dl) were all significantly lower (p<0.001) than in control group (106.16+/-13.36 microg/dl). Similarly mean+/-SD of serum copper in PEM (82.73+/-16.35 microg/dl), Marasmus (93.72+/-9.77 microg/dl), Kwashiorkor (63.75+/-13.12 microg/dl) and Marasmic Kwashiorkor (86.52+/-8.68 microg/dl) were all also significantly lower (p<0.001) than in control group (135.88+/-11.88 microg/dl). It is evident from the study that serum zinc and copper level significantly decrease in children with PEM.

Objective: To study the contractile properties, metabolism and morphological characteristics of muscles submitted to prenatal and postnatal protein malnutrition., Methods: Animals were distributed into two groups: Control, normoprotein diet (CG; n = 15; 5/5/5), and Malnourished, hypoprotein diet (MG; n = 15; 5/5/5), and examined on the 7th, 14th, and 28th days of the experiment. Total body mass, weight, and the contractile properties and morphology of the anterior tibial muscle were assessed. Several 8 microm-thick tissue samples were taken from 7, 14, and 28 day old rats and stained with HE or subjected to NADH-TR or m-ATPase (pH = 4.4) techniques., Results: Body and muscle weight were lower in the malnourished group. On the 7th day of malnutrition, muscle samples exhibited fibers with smaller diameter, higher polymorphism and higher endomysial conjunctive tissue content. Histochemical methods were unable to precisely determine the types of fiber present. On the 14th day, there were smaller muscle fibers, more polymorphism, many of them with central nuclei and moderate endomysial conjunctive tissue content. With reference to contractile properties, the m-ATPase reaction identified both slow and fast fibers. The NADH-TR reaction revealed the following types of fiber: slow oxidative (SO), fast oxidative glycolytic (FOG) and fast glycolytic (FG). On the 28th day smaller, bunched muscle fibers varying shapes. All three types of fiber exhibited unclear recognition limits with respect to contraction and metabolism., Conclusion: Our experimental results suggest that, in addition to the reduction in numbers of fibers, malnutrition retards the differentiation of the morphological, metabolic, and contractile characteristics of skeletal muscle fibers in growing rats.

Objective: To evaluate the implementation of the World Health Organization guidelines for the treatment of children with severe acute malnutrition in a class I hospital., Patients and Methods: Descriptive and prospective study of 335 children under the age of 6, admitted between 2001 and 2005 for severe acute malnutrition (83%) and moderate acute malnutrition associated with illness (17%). The care of the children was provided by clinicians and medical staff trained under World Health Organization guidelines., Results: Kwashiorkor was a common result in children with severe acute malnutrition (60.8%); 58% were younger than 1 year old. Complications upon admission were diarrhea (68.4%) and anemia (51.1%), and the most common complication during hospital stay was sepsis (9%). Overall, 61.7% attained -1 standard deviation of weight for height after an average stay of 3 weeks in the hospital; 5.1% were sent to tertiary care hospitals. Overall, mortality during the 5 years was 5.7%, with sepsis the most common cause. In the first year, the mortality rate was 8.7%; it decreased to 4.0% in the last year. The mortality rate was significantly higher in children with edema. Children with moderate acute malnutrition had similar complications and mortality when compared with children with severe acute malnutrition (5.3%)., Conclusions: Once the World Health Organization guidelines were implemented, low mortality rates were achieved in children with severe acute malnutrition in class I hospitals.

Inter-hemispheric modulation has been extensively studied, as it is critical for human behavior and could be involved in the development of neuropsychiatric disorders, such as major depression, epilepsy and stroke. Malnutrition early in life can alter brain processes such as inter-hemispheric modulation and these alterations can persist into adulthood. Here, we used cortical spreading depression (CSD) as a neurophysiological parameter to investigate inter-hemispheric modulation in 19 well-nourished and 18 early-malnourished male adult rats. CSD was evoked on the right frontal region and monitored at two parietal points on the same hemisphere. After a 2 h baseline recording, fibers projecting from the left to the right hemisphere via the corpus callosum were cut with a longitudinal lesion in the contralateral cortex and recording continued for two more hours. The results show that (1) baseline CSD propagation velocities were higher in the malnourished rats, as compared to the respective well-nourished controls; (2) post-lesion velocities increased in both nutritional groups, as compared with the baseline values; (3) this CSD increase persisted 3-7 days after lesion, suggesting a lasting effect and (4) in the malnourished group the post-lesion CSD enhancement was of smaller amplitude. Furthermore, a midline lesion (callosotomy) in eight well-nourished rats similarly facilitated CSD, suggesting the involvement of callosal fibers on this effect. No differences were found in sham-operated rats (21 well-nourished and 21 malnourished), as well as in a superficial (1 mm deep) contralateral lesion group (8 well-nourished). Results support the hypothesis of a lasting inhibitory contralateral influence on CSD propagation, which is attenuated, but not abolished, by early malnutrition.

In 30- and 90-day-old rats, using immunohistochemistry for glutamic acid decarboxylase 67 (GAD-67), we have tested whether malnutrition during different periods of hippocampal development produces deleterious effects on the population of GABA neurons in the dentate gyrus (DG) and cornu Ammonis (CA1-3) of the dorsal hippocampus. Animals were under one of four nutritional conditions: well-nourished controls (Con), prenatal protein malnourished (PreM), postnatal protein malnourished (PostM), and chronic protein malnourished (ChroM). We found that the number of GAD-67-positive (GAD-67+) interneurons was higher in the DG than in the CA1-3 areas of both Con and malnourished groups. Regarding the DG, the number of GAD-67+ interneurons was increased in PreM and PostM and decreased in ChroM at 30 days. At 90 days of age the number of GAD-67+ interneurons was increased in PostM and ChroM and remained unchanged in PreM. With respect to CA1-3, the number of labeled interneurons was decreased in PostM and ChroM at 30 days of age, but no change was found in PreM. At 90 days no changes in the number of these interneurons were found in any of the groups. These observations suggest that 1) the cell death program starting point is delayed in DG GAD-67+ interneurons, and 2) protein malnutrition differentially affects GAD-67+ interneuron development throughout the dorsal hippocampus. Thus, these changes in the number of GAD-67+ interneurons may partly explain the alterations in modulation of dentate granule cell excitability, as well as in the emotional, motivational, and memory disturbances commonly observed in malnourished rats.

Protein-energy malnutrition (PEM) modifies resistance to infection, impairing a number of physiological processes, including hematopoiesis. In this study, we examined a few aspects of the inflammatory response to LPS in a model of PEM. We evaluated the cellularity of the blood, bone marrow and spleen, as well as phagocytic, fungicidal and spreading activity, the production in vivo and in vitro of TNF-alpha, IL-1alpha and IL-6, and the expression of CD14 and TLR-4/MD-2 receptors in macrophages. Two-month-old male Swiss mice were submitted to PEM with a low-protein diet containing 4% protein as compared to 20% protein in the control diet. When the experimental group had attained about 20% loss of their original body weight, they were used in the experiments. Malnourished animals presented anemia, leucopenia and severe reduction in bone marrow, spleen and peritoneal cavity cellularity. The production of TNF-alpha, IL-1alpha and IL-6 stimulated in vivo with LPS and the production of IL-6 in bone marrow cells cultured with LPS and the production of TNF-alpha in bone marrow, spleen and peritoneal cells cultured with LPS were significantly lower in malnourished animals. The expression of CD14 and TLR-4/MD-2 receptors was found to be significantly lower in macrophages of malnourished animals. These findings suggest that malnourished animals present a deficient response to LPS. The lower expression of the CD14 and TLR-4/MD-2 receptors may be partly responsible for the immunodeficiency observed in the malnourished mice. These data lead us to infer that the nutritional state interferes with the activation of macrophages and with the capacity to mount an immune response.