Protein Deficit Research Articles

Alterações cutâneas no Kwashiorkor: relato de caso de um homem adulto após cirurgia abdominal

Kwashiorkor is a type of protein-energy malnutrition where diet protein deficit is found, in spite of appropriate caloric intake. Cutaneous manifestations include xerosis, with abnormally dry skin that has a flaking enamel paint aspect, a typical red to gray-white hair color, the "flag sign" and more evident edema in lower limbs and face, giving it a full moon appearance. This article reports a case of a male adult patient who had undergone Whipple surgery for treatment of chronic pancreatitis associated with pseudotumor of the pancreatic head that progressed to cutaneous manifestations of kwashiorkor after pulmonary tuberculosis.

Ishemia-Reperfusion enhances GAPDH nitration in aging skeletal muscle

Aging and skeletal muscle ischemia/reperfusion (I/R) injury leads to decreased contractile force generation that increases severely with age. Our studies show that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) protein expression is significantly decreased at 3 and 5 days reperfusion in the young mouse muscle and at 1, 3, 5, and 7 days in the aged muscle. Using PCR, we have shown that GAPDH mRNA levels in young and old muscle increase at 5 days reperfusion compared to control, suggesting that the protein deficit is not transcriptional. Furthermore, while total tyrosine nitration did not increase in the young muscle, GAPDH nitration increased significantly at 1 and 3 days reperfusion. In contrast, total tyrosine nitration in aged muscle increased significantly at 1, 3, and 5 days of reperfusion, with increases in GAPDH nitration at the same time points. We conclude that GAPDH protein levels decrease following I/R, that this is not transcriptionally mediated, that the aged muscle experiences greater oxidative stress, protein modification and GAPDH degradation, possibly contributing to decreased muscle function. We propose that tyrosine nitration enhances GAPDH degradation following I/R and that the persistent decrease of GAPDH in aged muscle is due to the prolonged increase in oxidative modification in this age group.

A Noninvasive Method for Estimating Nitrogen Balance in Free-Ranging Primates

The vital role of body protein as an energy reserve has received little focus in studies of wild primates. Owing to the relatively low protein content of fruit, some frugivorous primates could face a protein deficit if body protein is catabolized for energy during periods of low fruit availability. Such an imbalance can be detected if fatty acids, amino acids, and nitrogen (N) catabolites are reincorporated or recycled back to tissues. Here we describe a method to quantify protein recycling by measuring standardized urea concentration and N isotope signatures from urine samples collected from wild Bornean orangutans (Pongo pygmaeus wurmbii). Our overall goal was to explore if concentrations of urea and δ15N values could be used as indicators of the amount of protein consumed and the degree of protein recycling, respectively, in wild, free-ranging primates. We examine the relationships between urea concentration, δ15N values, protein intake, and fruit availability. Urea concentration increased with fruit availability, reflecting a slight increase in protein consumption when fruit was abundant. However, we found no relationship between δ15N values and fruit availability, suggesting that orangutans avert a negative protein balance during periods of low fruit availability. These noninvasive methods complement recent advances in primate energy balance research and will contribute to our understanding of adaptations of primates during periods of fruit shortage.

Reduction in postnatal cumulative nutritional deficit and improvement of growth in extremely preterm infants

To evaluate the influence of gestational age (GA) on cumulative nutritional deficit and postnatal growth in extremely preterm (EPT) infants after optimizing nutritional protocol as recently recommended. A prospective, nonrandomized, observational study in extremely preterm (EPT, <28 weeks) and very preterm (VPT, 28-30 weeks) infants. Eighty-four infants were included (BW: 978 ± 156 g, GA: 27.8 ± 1.3 weeks). Cumulative nutritional deficit increased during first week of life to -290 ± 84 and -285 ± 117 kcal/kg and -4.2 ± 3.1 and -4.8 ± 3.9 g/kg of protein in EPT and VPT groups, respectively. After 6 weeks, only cumulative energy deficit in EPT group remained significant (p < 0.05) even when 96% of theoretical energy intakes were provided. Weight z score decreased during first 3 days in average with initial weight loss, and then, the z score increased during the first 6 weeks of life in the majority (75%) of infants. Cumulative protein deficit during the first week of life was the major determinant of the postnatal growth during the first 6 weeks of life. Cumulative nutritional deficit may be drastically reduced in both EPT and VPT infants after optimizing nutritional policy during the first weeks of life, and the postnatal growth restriction could even be prevented.

Voluntary physical activity and leucine correct impairments in muscle protein synthesis in partially pancreatectomised rats

Poorly controlled type 1 diabetes mellitus can cause reduced skeletal muscle mass and weakness during adolescence, which may affect long-term management of the disease. The aim of this study was to determine whether regular voluntary physical activity and leucine feeding restore rates of protein synthesis and deficits in skeletal muscle mass in a young, hypoinsulinaemic/hyperglycaemic rat model of diabetes. Four-week-old male Sprague-Dawley rats were partially pancreatectomised (Px) to induce hypoinsulinaemia/hyperglycaemia and housed with/without access to running wheels for 3 weeks (n = 12-14/group). Sham surgery rats (shams) served as sedentary controls (n = 18). Protein synthesis and markers of protein anabolism were assessed in the fasted state and following leucine gavage. Fibre type and cross-sectional areas of the gastrocnemius muscle were measured using a metachromatic ATPase stain. Compared with sedentary behaviour, regular activity lowered fasting glycaemia and reduced fed hyperglycaemia in Px rats. Active-Px rats, which ran 2.2 ± 0.71 km/night, displayed greater muscle mass and fibre areas similar to shams, while sedentary-Px rats displayed a 20-30% loss in muscle fibre areas. Muscle protein synthesis (basal and in response to leucine gavage) was impaired in sedentary-Px (by ~65%), but not in active-Px rats, when compared with shams. Following leucine gavage, the phosphorylation status of eIF4E binding protein 1 (4E-BP1) and ribosomal S6 kinase 1 (S6K1), markers of mammalian target of rapamycin complex 1 (mTORC1) signalling, increased in shams (by two- and ninefold, respectively) and in active-Px (1.5- and fourfold, respectively) rats, but not in sedentary-Px rats. Moderate physical activity in young Px rats normalises impairments in skeletal muscle growth and protein synthesis. These findings illustrate the critical compensatory role that modest physical activity and targeted nutrition can have on skeletal muscle growth during periods of hypoinsulinaemia in adolescent diabetes.

Protective Effects of Positive Lysosomal Modulation in Alzheimer's Disease Transgenic Mouse Models

Alzheimer's disease (AD) is an age-related neurodegenerative pathology in which defects in proteolytic clearance of amyloid β peptide (Aβ) likely contribute to the progressive nature of the disorder. Lysosomal proteases of the cathepsin family exhibit up-regulation in response to accumulating proteins including Aβ1–42. Here, the lysosomal modulator Z-Phe-Ala-diazomethylketone (PADK) was used to test whether proteolytic activity can be enhanced to reduce the accumulation events in AD mouse models expressing different levels of Aβ pathology. Systemic PADK injections in APPSwInd and APPswe/PS1ΔE9 mice caused 3- to 8-fold increases in cathepsin B protein levels and 3- to 10-fold increases in the enzyme's activity in lysosomal fractions, while neprilysin and insulin-degrading enzyme remained unchanged. Biochemical analyses indicated the modulation predominantly targeted the active mature forms of cathepsin B and markedly changed Rab proteins but not LAMP1, suggesting the involvement of enhanced trafficking. The modulated lysosomal system led to reductions in both Aβ immunostaining as well as Aβx-42 sandwich ELISA measures in APPSwInd mice of 10–11 months. More extensive Aβ deposition in 20-22-month APPswe/PS1ΔE9 mice was also reduced by PADK. Selective ELISAs found that a corresponding production of the less pathogenic Aβ1–38 occurs as Aβ1–42 levels decrease in the mouse models, indicating that PADK treatment leads to Aβ truncation. Associated with Aβ clearance was the elimination of behavioral and synaptic protein deficits evident in the two transgenic models. These findings indicate that pharmacologically-controlled lysosomal modulation reduces Aβ1–42 accumulation, possibly through intracellular truncation that also influences extracellular deposition, and in turn offsets the defects in synaptic composition and cognitive functions. The selective modulation promotes clearance at different levels of Aβ pathology and provides proof-of-principle for small molecule therapeutic development for AD and possibly other protein accumulation disorders.

Audit of energy and protein intake in infants < 32 weeks gestation, during the first 28 days of life: impact on growth

AimsTo compare energy and protein intake with recommendations1 in a sample of preterm infants for 28 days after birth and to study the impact this intake has on short term...

Impact of cumulative calorie and protein deficit in critically ill patients

Impact of cumulative calorie and protein deficit in critically ill patients

Prolonged treatment with pimelic o-aminobenzamide HDAC inhibitors ameliorates the disease phenotype of a Friedreich ataxia mouse model

Friedreich ataxia (FRDA) is an inherited neurodegenerative disorder caused by GAA repeat expansion within the FXN gene, leading to epigenetic changes and heterochromatin-mediated gene silencing that result in a frataxin protein deficit. Histone deacetylase (HDAC) inhibitors, including pimelic o-aminobenzamide compounds 106, 109 and 136, have previously been shown to reverse FXN gene silencing in short-term studies of FRDA patient cells and a knock-in mouse model, but the functional consequences of such therapeutic intervention have thus far not been described. We have now investigated the long-term therapeutic effects of 106, 109 and 136 in our GAA repeat expansion mutation-containing YG8R FRDA mouse model. We show that there is no overt toxicity up to 5months of treatment and there is amelioration of the FRDA-like disease phenotype. Thus, while the neurological deficits of this model are mild, 109 and 106 both produced an improvement of motor coordination, whereas 109 and 136 produced increased locomotor activity. All three compounds increased global histone H3 and H4 acetylation of brain tissue, but only 109 significantly increased acetylation of specific histone residues at the FXN locus. Effects on FXN mRNA expression in CNS tissues were modest, but 109 significantly increased frataxin protein expression in brain tissue. 109 also produced significant increases in brain aconitase enzyme activity, together with reduction of neuronal pathology of the dorsal root ganglia (DRG). Overall, these results support further assessment of HDAC inhibitors for treatment of Friedreich ataxia.

Orally fed patients are at high risk of calorie and protein deficit in the ICU

Malnutrition can lead to serious complications in the ICU. Less than half of patients admitted to ICU require ventilation and for many, their optimal route of feeding is oral medical nutrition therapy, rather than enteral or parenteral nutrition. Inadequate oral intake is a prevalent and often difficult problem within this population, as increased calorie deficits are common in the ICU and associated with worse outcomes. Consuming less than 75% of daily calorie requirements in the hospital setting is associated with worse outcomes. Unfortunately, oral intake is often inadequate. Little is known about the consequences of inadequate oral intake in the ICU; however, data have described worse outcomes with large calorie deficits from enteral and parenteral nutrition. Whether or not these data can be extrapolated to patients in the ICU with poor oral intake remains uncertain. Despite evidence-based guidelines directing the delivery of nutrition support in the ICU, there is limited research focused on oral intake during this time of hospitalization. Future research is needed to determine the long-term associations of inadequate versus adequate oral intake in the ICU.

Count on the Dietician, and Common Sense

Count on the Dietician, and Common Sense

Impact of cumulative calorie and protein deficits in critically ill patients

This study aims to assess the outcome of cumulative protein and calorie deficits in critically ill patients.

Constitutive, but Not Challenge-Induced, Interleukin-10 Production Is Robust in Acute Pre-Pubescent Protein and Energy Deficits: New Support for the Tolerance Hypothesis of Malnutrition-Associated Immune Depression Based on Cytokine Production in vivo

The tolerance model of acute (i.e., wasting) pre-pubescent protein and energy deficits proposes that the immune depression characteristic of these pathologies reflects an intact anti-inflammatory form of immune competence that reduces the risk of autoimmune reactions to catabolically released self antigens. A cornerstone of this proposition is the finding that constitutive (first-tier) interleukin(IL)-10 production is sustained even into the advanced stages of acute malnutrition. The IL-10 response to inflammatory challenge constitutes a second tier of anti-inflammatory regulation and was the focus of this investigation. Weanling mice consumed a complete diet ad libitum, a low-protein diet ad libitum (mimicking incipient kwashiorkor), or the complete diet in restricted daily quantities (mimicking marasmus), and their second-tier IL-10 production was determined both in vitro and in vivo using lipopolysaccharide (LPS) and anti-CD3 as stimulants of innate and adaptive defences, respectively. Both early (3 days) and advanced (14 days) stages of wasting pathology were examined and three main outcomes emerged. First, classic in vitro systems are unreliable for discerning cytokine production in vivo. Secondly, in diverse forms of acute malnutrition declining challenge-induced IL-10 production may provide an early sign that anti-inflammatory control over immune competence is failing. Thirdly, and most fundamentally, the investigation provides new support for the tolerance model of malnutrition-associated inflammatory immune depression.

122 Postnatal Energy and Protein Deficits are Associated with Poor Neonatal Growth: Preliminary Results From a Swedish Population-Based Study

Background: Extremely preterm infants have extraordinarily high nutrient requirements and often show postnatal growth failure. It is still controversial, however, to what extent nutrition affects the weight development during the first weeks of life in these infants.Aim: To explore possible associations of accumulated intake of macronutrients and weight development during the first 28 days of life.Methods: All extremely preterm Swedish infants (< 27 gestational weeks) born between April 2004 and March 2007 (the EXPRESS-study) who survived >24 hours (n=600). Parenteral and enteral nutrition data and anthropometric data for the first 28 days were collected. Data are mean±SD.Results: Preliminary analyses of data from 152 infants (84 boys, gestational age 25.2±1.0 weeks, birth weight 756±168g, birth length 32.2±2.6 cm and head circumference 23.2±1.5 cm) showed that during the first 28 days of postnatal life, mean fluid intake was 164±17ml/kg/d, energy 97±13kcal/kg/d, protein 2.9±0.5g/kg/d, carbohydrates 11.0±1.1g/kg/d and fat 4.6±1.2g/kg/d. From birth to 28 days, ΔSDS was -2.2 SD for weight, -2.3 SD for length and -1.4 SD for head circumference. There was a significant correlation between ΔSDS for weight and protein intake (r=+0.50), energy intake (r=+0.44) and fat intake (r=+0.39) (p< 0.001 for all).Conclusions: Extremely preterm Swedish infants receive lower amounts of macronutrients, especially protein and energy, compared with current recommendations, and show significant postnatal growth failure. Our observation of significant positive associations between macronutrient intakes and weight change implies that improved early nutrient intakes may be one way to prevent postnatal growth retardation in these infants.

1057 Nutritional Deficit Among Extremely Low Birth Weight Infants is Evitable

Postnatal malnutrition and growth retardation were shown as inevitable consequence of current recommendations in preterm infants. In 2006, we modified our nutritional guideline: Objectives: To compare energy and protein cumulative deficits over the first seven weeks of life. Method: Optimal energy and protein intakes were set at 120Cal/kg.d and 3g/kg.d respectively and used to calculate positive cumulative deficits. We compared 2 groups of ELBW infants below 28 weeks born in 2005 and 2009 who stayed at least 7 weeks in our unit. Results are reported as median (Q1, Q3). Mann-Whitney tests were performed for each criteria. Results: Groups were not different for GA (p=0.277) and BW (p=0.106). At the end of the 1st and the 7th week, energy and protein deficit were significantly reduced in the 2009 group. Energy (Cal/kg): W1:419(378, 450) versus 375(327, 421), p=0.002; W7: 983(724, 1355) versus 48(-270, 484), p< 0.01 Protein (g/kg): W1: 5.77(5.06, 7.72) versus -0.19(-1.4, 0.65), p< 0.01 ; W7 : 1.14(-6.55, 6.68) versus-18.72(-27, -12.62), p< 0.01. Conclusion: Higher parenteral intakes and close attention to enteral feeding allowed a reduction of nutritional deficit. Nonetheless, potential clinical effect had to be studied.

Atypical hemolytic uremic syndrome in the Tunisian population

Hemolytic uremic syndrome consists of a triad of acquired hemolytic anemia, thrombocytopenia and renal failure. Our objectives were to determine epidemiology, clinical and laboratory characteristics of patients with atypical hemolytic uremic syndrome (aHUS) to determine the relationship between the complement protein deficit and aHUS in the Tunisian population. We studied retrospectively four cases of atypical HUS in adults admitted in the Nephrology Department of Fattouma Bourguiba Universitary Hospital in Monastir between 2000 and 2008. Three patients had renal failure that required dialysis. One of them received kidney transplantation with no further recurrence of aHUS. Three patients had normal C3, C4, CFH, and FB levels, and in all patients anti-FH autoantibodies were absent. The kidney biopsy of one patient showed in addition to lupus glomerulonephritis histological findings consistent with TMA. A decrease in C3, C4 and CFH levels in this patient was found both before and after the cure. Nephrologists should be aware of autoimmune conditions and genetic abnormalities of the complement regulatory genes as possible pathogenic mechanisms in atypical HUS patients.

Early nutritional support and outcomes in ELBW infants

Extrauterine growth restriction is a common finding among extremely low birth weight infants at discharge from neonatal intensive care units. It has been associated with significant caloric and protein deficits that accumulate during the hospitalization and with slower growth velocity observed with major neonatal morbidities. Recommendations to provide early nutritional support, both parenteral and enteral, have evolved in response to concern about the impact of poor in-hospital growth on growth and neurodevelopmental outcomes in early childhood. This paper will review the evidence supporting the provision of early nutritional support to extremely preterm infants by examining the outcomes associated with such practices.

The blood level of transforming growth factor-β rises in the early stages of acute protein and energy deficit in the weanling mouse

Plasma transforming growth factor (TGF)-beta levels are high in the advanced stages of acute (wasting) pre-pubescent deficits of protein and energy. Consequently, this potently anti-inflammatory cytokine may help to sustain the depression of inflammatory immune competence in acute malnutrition. Our objective was to determine if plasma TGF-beta levels rise during the early stages of acute malnutrition and, secondarily, to confirm the elevation reported previously in advanced weight loss. In two experiments, male and female C57BL/6J mice, initially 19 d old, consumed ad libitum a complete purified diet (group C), or in restricted daily quantities (group R) or had free access to an isoenergetic low-protein diet (group LP). TGF-beta bioactivity in platelet-poor plasma was determined via inhibition of Mv1Lu mink lung cell proliferation after 3 d (Expt 1, early stage) or 14 d (Expt 2, advanced stage) of dietary intervention. At 3 d, mean plasma TGF-beta bioactivities were 802 (C), 2952 (R) and 4678 (LP) pg/ml, and after 14 d mean bioactivities were 1786 (C), 5360 (R) and 5735 (LP) pg/ml. At both time points, the malnourished groups differed from age-matched controls (P </= 0.05). Thus, metabolically distinct weanling systems mimicking paediatric marasmus (group R) and kwashiorkor (group LP) exhibit an early rise in blood TGF-beta concentration, and this cytokine joins corticosterone and IL-10 as a third anti-inflammatory hormone temporally positioned to contribute to the initiation (and maintenance) of malnutrition-associated immune depression. This investigation contributes new insight into the active anti-inflammatory form of immune competence that appears to prevail in acute pre-pubescent malnutrition.

Novel epigenetic regulation of skeletal muscle myosin heavy chain genes. Focus on “Differential epigenetic modifications of histones at the myosin heavy chain genes in fast and slow skeletal muscle fibers and in response to muscle unloading”

skeletal muscle is a highly plastic tissue, capable of responding and adapting to a variety of physiological stimuli, e.g., muscle loading and unloading. Multiple functional phenotypes of skeletal muscle exist throughout the body at the same time. For example, muscles required for antigravity support of the skeleton or sustained locomotion are generally slow-contracting, low force-generating, and relatively resistant to fatigue, while other muscles required for quick, powerful movements are generally fast-contracting, high force-generating, and easily fatigued. In fact, skeletal muscle phenotypes have been characterized using combinations of muscle properties, including metabolic, fatigability, color, innervation, or predominant contractile protein expression. Myosin heavy chain (MHC) is the most abundant protein in skeletal muscle, comprising ∼25% of the total protein content, and is a major component of the complex responsible for generating contractile force in skeletal muscle. At least nine MHC isoforms, each transcribed from their own gene, exist in mammalian striated muscle; but only slow type I MHC and various isoforms of fast type II (IIa, IIx/d, and IIb MHC isoforms) are present in adult limb skeletal muscle that is not undergoing regeneration (16). It is well established that skeletal muscle phenotype, particularly MHC gene expression, can be altered by different states of muscular activity or inactivity, as well as various hormonal and metabolic factors (1).

Immunobiochemical status of sheep exposed to periods of experimental protein deficit and realimentation

Immunobiochemical status of sheep exposed to periods of experimental protein deficit and realimentation was studied in 12 sheep (15 mo) randomly distributed into 2 equal groups and fed individually 2 different concentrate supplements along with wheat straw to provide 100% (normal protein, NP) or 50% (low protein, LP) of CP requirements. The study was comprised of 3 periods; during period 1 (0 to 13 wk) and 2 (14 to 26 wk) animals in the 2 groups were fed NP and LP diets, respectively; during period 3 (27 to 44 wk), animals in the LP group were switched over to NP diet to allow realimentation, whereas animals in the NP group remained on the same NP diet. Blood was collected from all groups at end of each period, and serum glucose, total protein, albumin (sAlb), globulin (sGlb), urea (sU), creatinine (sCr), cholesterol, triiodothyronine, and thyroxine concentrations were determined. During the same periods, the cell-mediated immune (CMI) response was measured by a delayed type hypersensitivity (DTH) assay and in vitro nitrite production by lymphocytes. At the end of periods 2 and 3, humoral immune response (HIR) was measured by sensitizing the sheep with Brucella abortus S99 antigen and measuring antibody titers on 0, 7, 14, 21, and 28 d postinoculation by ELISA. Feed intake decreased with prolonged protein deficit and showed recovery during period 3. Blood chemistry revealed reduced sAlb concentration in the LP group resulting in narrow sAlb:sGlb ratio, increased sCr concentrations (P = 0.008) accompanying a decreased (P = 0.004) sU:sCr ratio, and decreased glucose concentrations (P = 0.05). Other variables did not change significantly between the NP and LP groups. The DTH response at the end of period 1 and 2 showed marked (P = 0.008) effect of protein restriction on CMI. Nitrite production, basal and after lipopolysaccharide stimulation, was greater (P = 0.04) in the NP group. The HIR was less (P = 0.04) in the LP group during period 3. Realimentation of protein in the LP group during period 3 showed recovery in CMI and HIR. In conclusion, protein deprivation induced a decline in CMI and HIR in sheep accompanying alterations in related metabolic profile. However, a marked recovery was observed after realimentation.