Complementary Biomarker Assessment of Components Absorbed from Diet and Creatinine Excretion Rate Reflecting Muscle Mass in Dialysis Patients.

To prevent protein energy malnutrition (PEM) and accumulation of waste products, dialysis patients require diet adjustments. Dietary intake assessed by self-reported intakes often provides biased information and standard 24-h urinary excretion is inapplicable in dialysis patients. We aimed to assess dietary intake via a complementary, less biased biomarker method, and to compare this to dietary diaries. Additionally, we investigated the prospective association of creatinine excretion rate (CER) reflecting muscle mass with mortality. Complete intradialytic dialysate and interdialytic urinary collections were used to calculate 24-h excretion of protein, sodium, potassium, phosphate and creatinine in 42 chronic dialysis patients and compared with protein, sodium, potassium, and phosphate intake assessed by 5-day dietary diaries. Cox regression analyses were employed to investigate associations of CER with mortality. Mean age was 64 ± 13 years and 52% were male. Complementary biomarker assessed (CBA) and dietary assessed (DA) protein intake were significantly correlated (r = 0.610; p < 0.001), but there was a constant bias, as dietary diaries overestimated protein intake in most patients. Correlations were found between CBA and DA sodium intake (r = 0.297; p = 0.056), potassium intake (r = 0.312; p = 0.047) and phosphate uptake/intake (r = 0.409; p = 0.008). However, Bland-Altman analysis showed significant proportional bias. During a median follow-up of 26.6 (25.3⁻31.5) months, nine dialysis patients (23%) died. CER was independently and inversely associated with survival (HR: 0.59 (0.42⁻0.84); p = 0.003). Excretion measurements may be a more reliable assessment of dietary intake in dialysis patients, as this method is relatively free from biases known to exist for self-reported intakes. CER seems to be a promising tool for monitoring PEM.

Selenium and zinc protect brain mitochondrial antioxidants and electron transport chain enzymes following postnatal protein malnutrition.

AIMS: Selenium (Se) and zinc (Zn) are trace elements required for optimal brain functions. Thus, the role of Se and Zn against protein malnutrition induced oxidative stress on mitochondrial antioxidants and electron transport chain (ETC) enzymes from rats' brain were investigated. MAIN METHODS: Normal protein (NP) and low protein (LP) rats were fed with diets containing 16% and 5% casein respectively for a period of 10weeks. Then the rats were supplemented with Se and Zn at a concentration of 0.15mgL(-1) and 227mgL(-1) in drinking water for 3weeks after which the rats were sacrificed. KEY FINDINGS: The results obtained from the study showed significant (p<0.05) increase in lipid peroxidation (LPO), ROS production, oxidized glutathione (GSSG) levels and mitochondrial swelling and significant (p<0.05) reductions in catalase (CAT) and Mn-superoxide dismutase (Mn-SOD) activities, glutathione (GSH) levels, GSH/GSSG ratio and MTT reduction as a result of LP ingestion. The activities of mitochondrial ETC enzymes were also significantly inhibited in both the cortex and cerebellum of LP-fed rats. Supplementation with either Se or Zn restored the alterations in all the parameters. SIGNIFICANCE: The study showed that Se and Zn might be beneficial in protecting mitochondrial antioxidants and ETC enzymes against protein malnutrition induced oxidative stress.

Leucine supplementation improves acquired growth hormone resistance in rats with protein-energy malnutrition.

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.

Nutritional recovery with okara diet prevented hypercholesterolemia, hepatic steatosis and glucose intolerance.

We assessed the biological value of an okara diet and its effects on the hormonal and metabolic profile of rats submitted to protein restriction during intra-uterine life and lactation and recovered after weaning. Male rats from mothers fed either 17% or 6% protein during pregnancy and lactation were maintained on 17% casein (CC, LC), 17% okara (CO, LO) or 6% casein (LL) diets over 60 d. The nutritional quality of the okara protein was similar to that of casein. The okara diet was effective in the nutritional recovery of rats in growing that were malnourished in early life. Furthermore, the okara diet reversed the hypercholesterolemia and the hepatic steatosis observed in the malnutrition and prevented glucose intolerance in an animal model prone to diabetes mellitus.

Differences in nutritional status between very mild Alzheimer's disease patients and healthy controls.

BACKGROUND: Studies on the systemic availability of nutrients and nutritional status in Alzheimer's disease (AD) are widely available, but the majority included patients in a moderate stage of AD. OBJECTIVE: This study compares the nutritional status between mild AD outpatients and healthy controls. METHODS: A subgroup of Dutch drug-naïve patients with mild AD (Mini-Mental State Examination (MMSE) ≥20) from the Souvenir II randomized controlled study (NTR1975) and a group of Dutch healthy controls were included. Nutritional status was assessed by measuring levels of several nutrients, conducting the Mini Nutritional Assessment (MNA®) questionnaire and through anthropometric measures. RESULTS: In total, data of 93 healthy cognitively intact controls (MMSE 29.0 [23.0-30.0]) and 79 very mild AD patients (MMSE = 25.0 [20.0-30.0]) were included. Plasma selenium (p < 0.001) and uridine (p = 0.046) levels were significantly lower in AD patients, with a similar trend for plasma vitamin D (p = 0.094) levels. In addition, the fatty acid profile in erythrocyte membranes was different between groups for several fatty acids. Mean MNA screening score was significantly lower in AD patients (p = 0.008), but not indicative of malnutrition risk. No significant differences were observed for other micronutrient or anthropometric parameters. CONCLUSION: In non-malnourished patients with very mild AD, lower levels of some micronutrients, a different fatty acid profile in erythrocyte membranes and a slightly but significantly lower MNA screening score were observed. This suggests that subtle differences in nutrient status are present already in a very early stage of AD and in the absence of protein/energy malnutrition.

A patient with CKD and poor nutritional status.

Protein energy wasting is common in patients with CKD and ESRD and is associated with adverse clinical outcomes, such as increased rates of hospitalization and death, in these patients. A multitude of factors can affect the nutritional and metabolic status of patients with CKD, including decreased dietary nutrient intake, catabolic effects of renal replacement therapy, systemic inflammation, metabolic and hormonal derangements, and comorbid conditions (such as diabetes and depression). Unique aspects of CKD also confound reliable assessment of nutritional status, further complicating management of this comorbid condition. In patients in whom preventive measures and oral dietary intake from regular meals cannot help them maintain adequate nutritional status, nutritional supplementation, administered orally, enterally, or parenterally, is effective in replenishing protein and energy stores. The advantages of oral nutritional supplements include proven efficacy, safety, and compliance. Anabolic steroids and exercise, with nutritional supplementation or alone, improve protein stores and represent potential additional approaches for the treatment of PEW. There are several emerging novel therapies, such as appetite stimulants, anti-inflammatory interventions, and anabolic agents.

Taurine supplementation restores insulin secretion and reduces ER stress markers in protein-malnourished mice.

Endoplasmic reticulum (ER) stress is a cellular response to increased intra-reticular protein accumulation or poor ER function. Chronic activation of this pathway may lead to beta cell death and metabolic syndrome (MS). Poor nutrition during perinatal period, especially protein malnutrition, is associated with increased risk for MS in later life. Here, we analyzed the effects of taurine (TAU) supplementation upon insulin secretion and ER stress marker expression in pancreatic islets and in the liver from mice fed a low-protein diet. Malnourished mice had lower body weight and plasma insulin. Their islets secreted less insulin in response to stimulatory concentrations of glucose. TAU supplementation increased insulin secretion in both normal protein and malnourished mice. Western blot analysis revealed lower expression of the ER stress markers CHOP and ATF4 and increased phosphorylation of the survival protein Akt in pancreatic islets of TAU-supplemented mice. The phosphorylation of the mitogenic protein extracellular signal-regulated kinase (ERK1/2) was increased after acute incubation with TAU. Finally, the ER stress markers p-PERK and BIP were increased in the liver of malnourished mice and TAU supplementation normalized these parameters.In conclusion, malnutrition leads to impaired islet function which is restored with TAU supplementation possibly by increasing survival signals and lowering ER stress proteins. Lower ER stress markers in the liver may also contribute to the improvement of insulin action on peripheral organs.

Effect of a probiotic fermented milk on the thymus in Balb/c mice under non-severe protein-energy malnutrition.

Protein­energy malnutrition (PEM) causes a significant impairment of the immune system, the thymus being one of the most affected organs. It has been demonstrated that the administration of probiotic fermented milk (PFM) recovered the intestinal barrier, histological alterations and mucosal and systemic immune functions in a non-severe malnutrition model using BALB/c mice. The aim of the present study was to evaluate, in the same model of malnutrition, the effect of a PFM added to a re-nutrition diet on the recovery of the thymus, analysing histological and functional alterations caused by malnutrition. Mice were undernourished and divided into three groups according to the dietary supplement received during re-nutrition: milk, PFM or its bacterial-free supernatant (BFS). They were compared with well-nourished and malnourished mice. PFM was the most effective re-nutrition supplement to improve the histology of the thymus, decreasing cellular apoptosis in this organ and recovering the percentage of CD4þ/CD82 single-positive thymocytes. Immature doublepositive thymocytes were increased in the malnourished control (MC). The production of different cytokines in the thymus was increased in mice given PFM, compared with the mice that received other dietary supplements and MC. Mice given the BFS presented an improvement in the thymus similar to those that received milk. We demonstrated the importance of the whole PFM supplementation on the histological and functional recovery of the thymus in a non-severe PEM model.

Modulation of the nuclear factor-kappa B (NF-κB) signalling pathway by glutamine in peritoneal macrophages of a murine model of protein malnutrition.

BACKGROUND AND AIMS: Protein malnutrition affects resistance to infection by impairing the inflammatory response, modifying the function of effector cells, such as macrophages. Recent studies have revealed that glutamine-a non-essential amino acid, which could become conditionally essential in some situations like trauma, infection, post-surgery and sepsis-is able to modulate the synthesis of cytokines. The aim of this study was to evaluate the effect of glutamine on the expression of proteins involved in the nuclear factor-kappa B (NF-κB) signalling pathway of peritoneal macrophages from malnourished mice. METHODS: Two-month-old male Balb/c mice were submitted to protein-energy malnutrition (n = 10) with a low-protein diet containing 2 % protein, whereas control mice (n = 10) were fed a 12 % protein-containing diet. The haemogram and analysis of plasma glutamine and corticosterone were evaluated. Peritoneal macrophages were pre-treated in vitro with glutamine (0, 0.6, 2 and 10 mmol/L) for 24 h and then stimulated with 1.25 µg LPS for 30 min, and the synthesis of TNF-α and IL-1α and the expression of proteins related to the NF-κB pathway were evaluated. RESULTS: Malnourished animals had anaemia, leucopoenia, lower plasma glutamine and increased corticosterone levels. TNF-α production of macrophages stimulated with LPS was significantly lower in cells from malnourished animals when cultivated in supraphysiological (2 and 10 mmol/L) concentrations of glutamine. Further, glutamine has a dose-dependent effect on the activation of macrophages, in both groups, when stimulated with LPS, inducing a decrease in TNF-α and IL-1α production and negatively modulating the NF-κB signalling pathway. CONCLUSIONS: These data lead us to infer that the protein malnutrition state interferes with the activation of macrophages and that higher glutamine concentrations, in vitro, have the capacity to act negatively in the NF-κB signalling pathway.

Effects of peritoneal dialysis on protein metabolism.

Protein-energy wasting is relatively common in renal patients treated with haemodialysis or peritoneal dialysis (PD) and is associated with worse outcome. In this article, we review the current state of our knowledge regarding the effects of PD on protein metabolism and the possible interactions between PD-induced changes in protein turnover and the uraemia-induced alterations in protein metabolism. Available evidence shows that PD induces a new state in muscle protein dynamics, which is characterized by decreased turnover rates and a reduced efficiency of protein turnover, a condition which may be harmful in stress conditions, when nutrient intake is diminished or during superimposed catabolic illnesses. There is a need to develop more effective treatments to enhance the nutritional status of PD patients. New approaches include the use of amino acid/keto acids-containing supplements combined with physical exercise, incremental doses of intraperitoneal amino acids, vitamin D and myostatin antagonism for malnourished patients refractory to standard nutritional therapy.

Decreased insulin secretion in islets from protein malnourished rats is associated with impaired glutamate dehydrogenase function: effect of leucine supplementation.

We herein studied the role of glutamate dehydrogenase (GDH), in response to leucine (LEU) supplementation, upon insulin secretion of malnourished rats. Weaned male Wistar rats were fed normal-protein (17%) or low-protein diet (6%, LP) for 8 weeks. Half of the rats of each group were supplemented with LEU (1.5%) in the drinking water for the following 4 weeks. Gene and protein expressions, static insulin secretion, and cytoplasmic Ca(2+) oscillations were measured. Glutamate dehydrogenase messenger RNA was 58% lower in LP islets, and LEU supplementation augmented it in 28%. The LP islets secreted less insulin when exposed to 20 mmol/L LEU, 20 mmol/L LEU + 2 mmol/L glutamine (with or without 5 mmol/L aminooxyacetic acid, a branched chain aminotransferase inhibitor, or 20 µmol/L epigallocatechin gallate, a GDH inhibitor), 20 mmol/L α-ketoisocaproate, glutamine + 20 mmol/L ß-2-aminobicyclo[2.2.1]heptane-2-carboxylic acid (a GDH activator), and 22.2 mmol/L glucose. Leucine supplementation augmented insulin secretion to levels found in normal-protein islets in all the above conditions, an effect that was blunted when islets were incubated with epigallocatechin gallate. The glutamine + ß-2-aminobicyclo[2.2.1]heptane-2-carboxylic acid-induced increased [Ca(2+)](i) and oscillations were higher than those for LP islets. Leucine supplementation normalized these parameters in LP islets. Impaired GDH function was associated with lower insulin release in LP islets, and LEU supplementation normalized insulin secretion via restoration of GDH function. In addition, GDH may contribute to insulin secretion through ameliorations of Ca(2+) handling in LP islets.

[Amino acid loss during dialysis treatment]. / Perdita di aminoacidi nel corso di terapia emodialitica extracorporea.

Protein-calorie malnutrition is a widespread complication in hemodialysis (HD) patients and is associated with increased mortality. The pathogenesis of malnutrition is multifactorial. Intradialytic amino acid (AA) loss is considered one of the cofactors in the complex mechanisms that lead to malnutrition in HD patients. It has been documented that in each dialysis session there is a 6-8 gram loss of AA into the dialysate, which worsens with the use of high-flux membranes. The intradialytic AA loss is variably compensated by reduction of liver synthesis and increased AA release from muscle stores. In malnourished HD patients the serum AA concentration, especially branched-chain AA (BCAA), is correlated with nutritional status and anorexia, whereas BCAA supplementation improves the nutritional parameters and increases appetite. Further studies are necessary to clarify the role of alterations of AA metabolism in the pathogenesis of malnutrition and the potential beneficial effects of BCAA supplementation or alternative treatments in malnourished patients.

Glutamine supplementation does not improve protein synthesis rate by the jejunal mucosa of the malnourished rat.

It has been demonstrated that glutamine, a conditionally essential amino acid, improves nitrogen balance, acts as a stimulant of protein synthesis, and decreases proteolysis in myopathic children. In contrast, other studies have shown no beneficial effect of glutamine supplementation on burn victims or critically ill patients. Nonetheless, we hypothesized that glutamine supplementation would increase the fractional protein synthesis rate (FSR) in the jejunal mucosa of malnourished male Wistar rats. Thus, the objective of the present study was to test the effect of daily oral glutamine supplementation (0.42 g kg(-1) d(-1) for 14 days) on the FSR of the jejunal mucosa of healthy and malnourished rats. A 4-hour kinetic study with l-[1-(13)C]leucine was subsequently performed, and jejunal biopsies were obtained 1.5 cm from the Treitz angle and analyzed. Malnourished rats showed a 25% weight loss and increased urinary nitrogen excretion. Plasma amino acid concentration did not differ between groups. (13)C enrichment in plasma and jejunal cells was higher in the malnourished groups than in the healthy group. The FSR (percent per hour) was similar for the control and experimental groups (P > .05), with a mean range of 22%/h to 27%/h. Oral glutamine supplementation alone did not induce higher protein incorporation by the jejunal mucosa in malnourished rats, regardless of total food intake or the presence or absence of glutamine supplementation.

Effects of cysteine on metformin pharmacokinetics in rats with protein-calorie malnutrition: partial restoration of some parameters to control levels.

Metformin is metabolized primarily via hepatic microsomal cytochrome P450 (CYP)2C11, CYP2D1 and CYP3A1/2 in rats. The expression and mRNA levels of hepatic CYP2C11 and CYP3A1/2 are decreased in rats with protein-calorie malnutrition (PCM), but these levels are fully or partially restored to control levels in PMC rats by oral cysteine supplementation (PCMC rats). Thus, it would be expected that the pharmacokinetic parameters of metformin in PCM rats would be returned to control levels in PCMC rats. Metformin was administered i.v. (100 mg kg(-1)) and orally (100 mg kg(-1)) to control, CC (control rats with oral cysteine supplementation), PCM and PCMC rats. The following pharmacokinetic parameters of metformin following i.v. administration were restored from levels in PCM rats to levels in control rats in PCMC rats: intrinsic clearance (0.0350, 0.0309, 0.0253 and 0.0316 mL min(-1) mg(-1) protein for control, CC, PCM, and PCMC rats, respectively), total area under the plasma concentration-time curve from time zero to time infinity (AUC; 4110, 4290, 5540 and 4430 microg min mL(-1), respectively), and time-averaged non-renal clearance (8.12, 7.95, 5.94 and 8.17 mL min(-1) kg(-1), respectively). AUC values following oral administration were comparable between control and PCMC rats (1520, 1480, 2290 and 1680 microg min mL(-1), respectively).

Effects of Cholerella sp. microalgae extract on colonic anastomosis in rats with protein-energy malnutrition.

OBJECTIVE: Algae, which are used as supplementary nutrients in various countries, are products rich in protein, vitamins and minerals. The aim of this study was to investigate the effects of algae extracts on the healing of colonic anastomosis in malnourished rats. METHOD: Seventy-two rats were randomized to three groups. Group 1 was fed with standard diet for 15 days, before and after the colonic anastomosis. Groups 2 and 3 were fed with a malnutrition diet for 15 days prior to colonic anastomosis and then with the basic diet for 15 days there after. Group 3 also received an extract of algae derived from Cholerella sp. via oral gavage postoperatively, in addition to the basic diet. Rats were killed on the 3rd, 7th and 15th postoperative day. Blood samples were collected to evaluate prealbumin, transferring and albumin levels. Anastomotic bursting pressures (BPs), histopathology and tissue hydroxyproline levels were evaluated after killing. RESULTS: In group 3, the prealbumin level on the 3rd postoperative day and transferrin and albumin levels on the 7th and 15th postoperative days were significantly increased compared with the other groups (P < 0.05). Tissue hydroxyproline levels and anastomotic BPs of group 3 were significantly higher than in group 2 on the 3rd, 7th and 15th postoperative days (P < 0.05). Histopathological examination of the anastomosis revealed significantly better healing patterns for group 3 than for groups 1 and 2 (P < 0.05). CONCLUSION: Extract derived from Cholerella sp. microalgae has favourable effects on healing of experimental colon anastomoses.

Hypovitaminosis D in internal medicine inpatients.

Some studies have suggested that hypovitaminosis D may be a consequence of protein-calorie malnutrition. This study assessed both the relationship between vitamin D status, malnutrition, calcium and phosphorus metabolism indices and the importance attached by internists to these alterations. There were 239 patients admitted to an internal medicine division who underwent examinations to assess nutritional state, liver and renal function, and bone metabolism. At the end of the study, the clinical data included in the discharge letter, the treatment prescribed, and the diagnosis assigned to patients on their hospital discharge form were collected. Hypovitaminosis D was found in 72% and hypoalbuminemia in 34.3% of patients. Subjects with hypovitaminosis were generally older and had lower albumin levels than those with mild or no hypovitaminosis. 25-Hydroxyvitamin D was inversely related with parathyroid hormone and directly related with albumin. Alterations of calcium and phosphorus metabolism were present in 55.6% and recorded by the division's physicians for only 13.53% of patients, of whom 72.37% were not specifically treated. There is a direct correlation between 25-hydroxyvitamin D and albumin levels. The high incidence and the metabolic consequence of hypovitaminosis D and of protein-calorie malnutrition is significantly underestimated and undertreated by physicians.

N-acetyl-L-glutamine, a liquid-stable source of glutamine, partially prevents changes in body weight and on intestinal immunity induced by protein energy malnutrition in pigs.

The goal of this study was to evaluate the preventive effect of free glutamine versus N-acetyl-L-glutamine, a liquid-stable source of glutamine, on gut damage induced by protein energy malnutrition in pigs. Healthy pigs (n = 6) were fed a liquid formula for 30 days. Three subgroups of malnourished pigs (n = 6) received daily 20% of the food intake recorded in control group, supplemented with calcium caseinate, glutamine, or N-acetyl-L-glutamine. Body weight was recorded, and small intestinal samples were evaluated for biochemical and immunologic parameters. Suppression in body weight gain was significantly lower in pigs fed with N-acetyl-L-glutamine than in the rest of malnourished pigs. Total number of lymphocytes, CD21+ B cells and CD4+ T cells in ileal Peyer patches were not significantly different in malnourished pigs fed with N-acetyl-L-glutamine and in healthy pigs. In conclusion, N-acetyl-L-glutamine has a moderate protective effect, partially preventing changes induced by protein energy malnutrition.

Effect of ivelip and sodium nitroprusside on 5-HT, glutathione and lipid peroxidation in normal and malnourished rat brain.

We examined the effect of experimental malnutrition and diet supplementation of parameters of central nervous system damage. Wistar rats were fed during 30 days and classified as malnourished (MN, 7% protein content diet) or well-nourished (WN, 23% protein content diet), were grouped and treated as follows: I-control; II-SNP (20 microg/kg); IIl-Ivelip (280 mg/kg) and IV-Ivelip + sodium nitroprusside (SNP). Levels of lipid peroxidation (TBARS), glutathione (GSH), tryptophan (Trp) and serotonin (5-HT) were assessed in brain by liquid chromatography. TBARS and GSH levels increased significantly (p < 0.05) in MN vs. WN rats that did not receive Ivelip. No significant differences were observed in TBARS and GSH among rats that received Ivelip or SNP. The weight of rats decreased significantly (p < 0.05) in all MN groups in relation to the WN groups. Hemoglobin (Hb) levels increased significantly (p < 0.05) in MN and WN groups that received Ivelip. 5-HT levels increased significantly (p < 0.05) in all MN groups. Trp levels increased significantly (p < 0.05) in the WN + Ivelip group vs. control. Early malnutrition induces changes in the metabolism of biogenic amines and this condition may promote oxidative injury of the brain.

Enhanced fracture and soft-tissue healing by means of anabolic dietary supplementation.

BACKGROUND: Malnutrition is common in hospitalized injured patients. It contributes to delayed fracture-healing and increased morbidity. However, relatively little attention has been directed toward nutritional strategies for augmenting musculoskeletal recovery after a fracture. This animal study was designed to examine the effects of dietary protein intake and the role of conditionally essential amino acids in muscle and bone-healing after a fracture. METHODS: One hundred adult male rats were used. Ten rats served as controls and received a 15% protein diet throughout the study. The remaining ninety rats received a 6% protein diet for five weeks to induce protein malnutrition. The rats underwent intramedullary nailing and closed midshaft fracture of one femur. After the fracture, they were separated into three isocaloric dietary groups. Group P6 received a diet with 6% protein; Group P15, a diet with 15% protein; and group P30, a diet with 30% protein with conditionally essential amino acids. At two, four, and six weeks after surgery, ten animals from each group were killed and the femora were evaluated with dual x-ray absorptiometry, histomorphometric assessment of callus, and torsional testing. The quadriceps muscles were analyzed for total mass, total protein content, and for mRNA expression of insulin-like growth factor-1 (IGF-1), IGF-2, IGF receptors, actin, myosin, and vascular endothelial growth factor (VEGF). RESULTS: The P30 group demonstrated elevations in albumin, body mass, muscle mass, total protein content of muscle, and bone mineral density in the fracture callus compared with the P6 diet group at six weeks (p < 0.05). Molecular analysis of muscle revealed that IGF-1, IGF-2, IGF receptors, myosin, actin, and VEGF gene expression were significantly (p < 0.001) higher in the P6 group compared with the P30 group. Biomechanical testing of the femora, however, showed no significant differences. CONCLUSIONS: Dietary supplementation with conditionally essential amino acids in malnourished animals had anabolic effects on bone mineralization, body mass, and muscle mass.

The gastroprotective effect of the essential oil of Croton cajucara is different in normal rats than in malnourished rats.

It has been shown previously that malnourished rats are resistant to acute gastric lesions but not to subchronic gastric ulceration. It also has been demonstrated that the essential oil obtained from the bark of Croton cajucara (Sacaca) has antiulcer properties. In the present study, the ability of this essential oil to prevent the formation of gastric ulcers in rats fed a diet with 17% protein (normoproteic rats) or 6% protein (malnourished rats) was investigated. At a dose of 100 mg/kg body weight, orally, the essential oil significantly reduced the gastric injury caused by indomethacin (25% after 2 h and 70% after 4 h) only in normoproteic rats. In the pylorus ligature model, the essential oil increased the pH and gastric volume, but decreased the total acid concentration in both groups when compared to the respective control group. The essential oil significantly increased prostaglandin E2 production in glandular cells by 50% compared to the controls in both groups of rats. In addition, the amount of gastric mucus was two-fold higher in malnourished rats than in normoproteic rats. The present results show that the enhanced protective effect of essential oil in malnourished rats involved an increase in prostaglandin E2 production and mucus secretion, which are both factors that protect the gastric mucosa against damage. In agreement with this, malnourished rats always had a lower number of acute gastric ulcers.