Free oxygen radical-induced lipid peroxidation and antioxidant in infants receiving total parenteral nutrition

OBJECTIVE: Increased oxygen-derived free radical activity has been reported during total parenteral nutrition (TPN) in infants particularly linked to the fat infusion. It is possible that partial enteral feeding can ameliorate some of the complications of TPN. By this study we aimed to investigate free radical formation and antioxidant activity in term and preterm infants during TPN and/or enteral feeding. STUDY DESIGN: We had 6 groups of term and preterm infants made up of 10 patients each. Group I had only enteral feeding, Group II enteral plus parenteral feeding, Group III only parenteral feeding. Plasma malondialdehyde (MDA), superoxide dismutase (SOD), vitamin E and vitamin C levels were measured in all infants. Blood samples of infants receiving only TPN and TPN plus enteral feeding were measured on the 1st and 5th days, and 3h after the end of lipid infusion. RESULTS: There was no difference between the term and preterm infants in terms of MDA, SOD, vitamin C and E levels taken baseline and after parenteral, and enteral plus parenteral feeding on the 1st and 5th days. When 3 groups of both term and preterm infants were compared with each other none of the parameters showed a statistically significant difference. In addition, we compared baseline and 1st and 5th days of TPN therapy in both term and preterm infants fed only parenterally and enteral plus parenteral feedings. In term infants fed both parenterally and parenteral plus enterally, the MDA levels before TPN were significantly higher than that of the levels of patients on parenteral nutrition on the 5th day. On the 1st and 5th days of TPN therapy, the levels of vitamin C was significantly decreased, in term and preterm infants fed only parenterally, levels of vitamin E was increased, in term and preterm infants fed both parenterally and parenteral plus enterally. Also, when compared to their base line the SOD levels of the term infants detected on the 1st and 5th days were significantly high. CONCLUSION: Free radical production is increased by the administration of TPN and may be linked to its adverse effects. It may be assumed that long-term complications of preterm infants receiving TPN may be reduced by further strengthening the antioxidant capacities of the TPN solutions.     

牛磺酸与生长发育

<正> 牛磺酸的发现已有160多年的历史,但其生物学功能在发现它的缺乏而致失明以后,其研究才迅速发展。近10年来,连续召开了8次有关牛磺酸作用的专题国际会议。研究表明,牛磺酸具有广泛的营养作用,尤其在心血管系统、中枢神经等方面具有重要的调节作用,其缺乏可引起多种疾病。例如婴儿早期缺乏可以引起生长发育的微细变化,最终导致学习、行为等方面障     

Influence of lung oxidant and antioxidant status on alveolarization: role of light-exposed total parenteral nutrition

Parenteral multivitamins (MVP) are linked to the generation of peroxides, which cause oxidant injury in lungs associated with alveolar remodelling linked to lung disease of prematurity. This study was to investigate the relationship between alveolar development and lung oxidant-antioxidant status as modulated by the mode of administration of multivitamins with total parenteral nutrition (TPN). Four groups of guinea pig pups received parenteral nutrition differing by 1) mode of MVP admixture: with amino acid solution (AA-MVP) or lipid emulsion (LIP-MVP); 2) light exposure: TPN exposed (LE) or shielded from light (LP). After 2 or 4 days of TPN, vitamins C and E, 8-isoprostaneF(2alpha) and alveolarization index were determined in lungs and GSSG/GSH in lungs and blood. Exposure to light and the mode of MVP admixture did not influence vitamin E and isoprostane levels. Blood glutathione redox potential was more oxidized in LE and LIP-MVP groups after 4-day infusions, whereas lung redox potential was more reduced in LE groups. LP and LIP-MVP had a beneficial effect, with higher number of alveoli. Globally, results indicate that in this model, alveolarization and modifications in lung redox potential are two independent events induced by light exposed TPN.     

Acidomucin goblet cell expansion induced by parenteral nutrition in the small intestine of piglets

Total parenteral nutrition (TPN) impairs small intestine development and is associated with barrier failure, inflammation, and acidomucin goblet cell expansion in neonatal piglets. We examined the relationship between intestinal goblet cell expansion and molecular and cellular indices of inflammation in neonatal piglets receiving TPN, 80% parenteral + 20% enteral nutrition (PEN), or 100% enteral nutrition (control) for 3 or 7 days. Epithelial permeability, T cell numbers, TNF-alpha and IFN-gamma mRNA expression, and epithelial proliferation and apoptosis were compared with goblet cell numbers over time. Epithelial permeability was similar to control in the TPN and PEN jejunum at day 3 but increased in the TPN jejunum by day 7. By day 3, intestinal T cell numbers were increased in TPN but not in PEN piglets. However, goblet cell expansion was established by day 3 in both the TPN and PEN ileum. Neither TNF-alpha nor IFN-gamma mRNA expression in the TPN and PEN ileum correlated with goblet cell expansion. Thus goblet cell expansion occurred independently of overt inflammation but in association with parenteral feeding. These data support the hypothesis that goblet cell expansion represents an initial defense triggered by reduced epithelial renewal to prevent intestinal barrier failure.     

Association of cholelithiasis with total parenteral nutrition and fasting in a preterm infant.

Cholelithiasis is uncommon in infants. A case of cholelithiasis in a preterm boy who required total parenteral nutrition (TPN) because of prolonged fasting is described. The diagnosis was confirmed by ultrasonography. Despite cholestasis, reintroduction of oral feeding and discontinuation of TPN resulted in the spontaneous disappearance of the gallstones.     

Comparaison de la réponse métabolique du petit prématuré alimenté parentéralement,puis au lait maternel de prématurité.

The nitrogen retention and plasma amino acid concentration were determined in eight preterm infants (mean birth weight 970 +/- 130 g; mean gestational age 28 +/- 1 weeks) receiving successively total parenteral nutrition and their own mother''s milk. The nitrogen retention during both regimens was comparable to the fetal accretion rate. Plasma amino acid concentrations were lower during the enteral phase of the study than during parenteral nutrition. The metabolic response of small preterm infants is related to the quality of amino acids as well as to the route of intake.     

Prevalence of Candida albicans in patients receiving total parenteral nutrition

The prevalence of Candida albicans was quantitatively compared in 74 surgical patients during and after total parenteral nutrition (TPN). Suppression of oral food intake is probably responsible for the decrease of the C. albicans population in the mouth. On the contrary anal swabs were more often positive for C. albicans during TPN. This may be due to local conditions as was observed in a group of patients who were not given TPN but were also immobilized for a long period.     

Absence of increase of serum alkaline phosphatase activity with parenteral nutrition-associated cholestasis: possible consequence of hypozincemia and hypomagnesemia

We reviewed charts of 38 Patients who developed cholestasis whilst receiving total parenteral nutrition (TPN). A standard protocol was followed for administration of TPN and included crystalline amino acid solution with lipid emulsion and dextrose as calorie sources. 5 of the 38 patients did not exhibit an increase in alkaline phosphatase. This may be related to the concomitant low levels of either serum zinc or magnesium or both. We also obtained a positive correlation between serum levels of zinc and magnesium and the peak activity of alkaline phosphatase (r = 0.49, p less than 0.01, r-0.55, p less than 0.01, respectively) associated with cholestasis. We hypothesize that the reason for this association is related to both zinc and magnesium being activators of alkaline phosphatase activity.     

Selenium in total parenteral nutrition

In clinical practice, selenium deficiency may arise under conditions of chronic malnutrition and especially after long-term total parenteral nutrition (TPN). In infants receiving long-term TPN, we observed plasma selenium levels as low as those previously reported in Chinese children with Keshan disease. Low plasma selenium levels were also usually associated with very low activities of glutathione peroxidase. Although clinical symptoms of selenium deficiency did not occur in our patients, several cases have been described in the literature, indicating the need for supplementation in TPN. In order to derive at the appropriate dosage, it is proposed to correlate it with the total protein supply. According to our present knowledge, .5–1.0 μg selenium/g of protein appears to be adequate to keep patients in Se balance. For Se repletion of body stores, this dosage has been increased up to 3 μg of Se/g of protein. Advantages and disadvantages of selenite and of selenomethionine as possible supplemental forms of Se for TPN solutions are discussed.     

An Exclusive Human Milk-Based Diet in Extremely Premature Infants Reduces the Probability of Remaining on Total Parenteral Nutrition: A reanalysis of the data

ABSTRACT: BACKGROUND: We have previously shown that an exclusively human milk-based diet is beneficial for extremely premature infants who are at risk for necrotizing enterocolitis (NEC). However, no significant difference in the other primary study endpoint, the length of time on total parenteral nutrition (TPN), was found. The current analysis re-evaluates these data from a different statistical perspective considering the probability or likelihood of needing TPN on any given day rather than the number of days on TPN. This study consisted of 207 premature infants randomized into three groups: one group receiving a control diet of human milk, formula and bovine-based fortifier ("control diet"), and the other two groups receiving only human milk and human milk-based fortifier starting at different times in the enteral feeding process (at feeding volumes of 40 or 100 mL/kg/day; "HM40" and "HM100", respectively). The counting process Cox proportional hazards survival model was used to determine the likelihood of needing TPN in each group. RESULTS: The two groups on the completely human-based diet had an 11-14 % reduction in the likelihood of needing nutrition via TPN when compared to infants on the control diet (p = 0.0001 and p = 0.001, respectively for the HM40 and HM100 groups, respectively). This was even more pronounced if the initial period of TPN was excluded (p < 0.0001 for both the HM40 and HM100 groups). CONCLUSIONS: A completely human milk-based diet significantly reduces the likelihood of TPN use for extremely premature infants when compared to a diet including cow-based products. This likelihood may be reduced even further when the human milk fortifier is initiated earlier in the feeding process. Trial registration This study was registered at www.clinicaltrials.gov reg. # NCT00506584.     

Multiplication of Nosocomial Pathogens in Intravenous Feeding Solutions

A major problem in total parenteral nutrition is sepsis, particularly that caused by Candida. Studies of four solutions, a casein hydrolysate, a fibrin hydrolysate, and two crystalline amino acid solutions, show that the protein hydrolysate solutions appear to be highly selective for Candida over bacteria, whereas the crystalline amino acid solutions are not. These findings suggest that the crystalline amino acid preparations may offer a partial solution to the infection problem by minimizing the contribution of the solution as a reservoir for organism multiplication, because they retard the growth of both bacteria and Candida.     

A porcine animal model to mimic the restart of enteral nutrition (refeeding-model)

With the aim towards establishing an animal model of total parenteral nutrition (TPN), 12 piglets aged 9 weeks (mean body weight 21 kg) were surgically provided with central venous catheters. Six piglets were nourished parenterally with the objective to reach a 14-d period of TPN; the other six piglets served as control and were fed normally. Only one animal from each group could be monitored over the whole period. Nine piglets were euthanised on d 13 and one on d 12. No animal showed fever or signs of septicaemia during the study. The levels of Ca, Mg, Na and P in the blood were within the normal range as were those for blood glucose and plasma creatinine. Symptoms of the TPN included: transient diarrhoea, occasional appearance of faecal blood and occasional absence of defecation. A reduced small intestine length and altered mucosal morphology and function were observed. One animal showed bile stasis at the end of the study. All TPN animals showed a remarkably high level of blood urea early in the morning. The intestinal symptoms observed may resemble the human situation during TPN. However, due to the fast growth rate, pigs aged 9 weeks have higher nutrient requirements per kg body weight. Consequently, the osmolality of the nutrient solution was necessarily high. Whether the significantly higher blood urea observed in the TPN group reflected a catabolic metabolism during the starving period at night-time could not be conclusively shown. Alternatively, it could reflect a slower growth rate and a resulting quantitative excess of amino acids (AA), or could have been the consequence of a suboptimal AA composition. A permanent infusion would be favourable in order not to overcharge the capacity for glucose uptake and amino acid metabolism during the infusion.     

Arginine and ornithine kinetics in severely burned patients: increased rate of arginine disposal

Arginine serves multiple roles in the pathophysiological response to burn injury. Our previous studies in burn patients demonstrated a limited net rate of arginine de novo synthesis despite a significantly increased arginine turnover (flux), suggesting that this amino acid is a conditionally indispensable amino acid after major burns. This study used [15N2-guanidino-5,5-2H2]arginine and [5-13C]ornithine as tracers to assess the rate of arginine disposal via its conversion to and subsequent oxidation of ornithine; [5,5-2H2]proline and [5,5,5-2H3]leucine were also used to assess proline and protein kinetics. Nine severely burned patients were studied during a protein-free fast ("basal" or fast) and total parenteral nutrition (TPN) feedings. Compared with values from healthy volunteers, burn injury significantly increased 1) fluxes of arginine, ornithine, leucine, and proline; 2) arginine-to-ornithine conversion; 3) ornithine oxidation; and 4) arginine oxidation. TPN increased arginine-to-ornithine conversion and proportionally increased irreversible arginine oxidation. The elevated arginine oxidation, with limited net de novo synthesis from its immediate precursors, further implies that arginine is a conditionally indispensable amino acid in severely burned patients receiving TPN.     

Influence of the glass packing on the contamination of pharmaceutical products by aluminium. Part II: Amino acids for parenteral nutrition

The presence of aluminium in amino acids parenteral nutrition solutions can be related to the affinity of the amino acids for aluminium present in glass containers used for storage. For this study solutions of 19 amino acids used in parenteral nutrition were stored individually in glass flasks and the aluminium measured at determined time intervals. Solutions of complexing agents for aluminium, as ethylene-diaminetetraacetic acid, nitrilotriacetic acid, citrate, oxalate and fluoride ions were also stored in the same flasks and the aluminium measured during the same time interval. The measurements were made by electrothermal atomic absorption spectrometry. The aluminium content of the glass containers was also measured. The results showed that the glasses have from 0.6% to 0.8% Al. Only solutions of cysteine, cystine, aspartic acid and glutamic acid became contaminated by aluminium. As the same occurred with the complexing agents, aluminum can be released from glass due to an affinity of the substances for aluminium. Comparing the action of complexing agents and amino acids for which the stability constants of aluminium complex are known, it is possible to relate the magnitude of the stability constant with the aluminium leached from glass, the higher the stability constant, the higher the aluminium released. The analysis of commercial formulations with and without cysteine, cystine, glutamic acid or aspartic acid stored in glass containers confirms that the presence of these amino acids combined with the age of the soLution are, at least partially, responsible for the aluminium contamination. The resuLts demonstrated that the contamination is an ongoing process due to the presence of aluminium in glass combined with the affinity of some amino acids for this element.     

Total parenteral nutrition adversely affects gut barrier function in neonatal piglets

Sepsis is the most common morbidity in preterm infants, who often receive total parenteral nutrition (TPN). We hypothesized that gut barrier function is compromised in TPN-fed compared with enterally fed newborn piglets (ENT pigs). Colostrum-deprived newborn pigs were implanted with jugular venous and bladder catheters under general anesthesia. Pigs were either administered TPN (n = 15) or fed formula (ENT pigs, n = 15). After 6 days, pigs were gavaged a solution of mannitol, lactulose, and polyethylene glycol 4000 (PEG 4000) and urine was collected for 24 h. At 7 days, small bowel samples were assayed for myeloperoxidase activity, morphometry, and tight junction protein abundance. Intestinal contents and peripheral organ sites were cultured for bacteria. Urinary recovery (%dose) of mannitol (53 vs. 68) was lower, whereas that of lactulose (2.93 vs. 0.18) and PEG 4000 (12.78 vs. 0.96) were higher in TPN vs. ENT pigs, respectively (P < 0.05). Incidence of translocation was similar in TPN and ENT pigs. Myeloperoxidase activity was increased in TPN vs. ENT pigs in the jejunum (P < 0.001) and was weakly correlated with lactulose (R2 = 0.32) and PEG 4000 (R2 = 0.38) recovery. Goblet cell counts did not change, but intraepithelial lymphocyte numbers decreased with TPN. Only claudin-1 protein abundance was increased in the TPN group. We conclude that TPN is associated with impairment of neonatal gut barrier function as measured by permeability but not translocation.     

Can elevated chromium induce somatopsychic responses?

The possible somatopsychological effects of chromium (Cr) was investigated in a population of patients, from a surgical ward of our hospital, who required total parenteral nutrition (TPN) solutions, and who became exposed to various amounts of this metal from this treatment. The study involved a questionnaire as well as biochemical tests which included serum Cr and other selected trace metals. The renal status for all eligible patients was within normal parameters. The patient population varied in age, pathology, surgical treatment, and duration on TPN. The results showed that every patient who received TPN had an increased serum Cr level; some increases were up to 50-fold above the normal reference level for serum Cr. Although statistical analysis failed to show any significant statistical relationship between an increased serum Cr and the investigated somatopsychological disturbances, this effect cannot be ruled out since one case did show all the dream disturbances: Considering these cases, the action of sedative medications that may suppress the effects of Cr, cannot be ruled out. As Cr(III) may be potentially genotoxic at high concentrations, infusion of this metal over long time periods should be avoided. Supplementation of Cr in TPN solutions appears to be unnecessary for short-term TPN because this metal is a known contaminant of these solutions. Efforts are required to find TPN nutrients with low or no Cr contamination.     

Highlight Commentary on "Influence of lung oxidant and antioxidant status on alveolarization: Role of light-exposed total parenteral nutrition"

Bronchopulmonary dysplasia (BPD) is a frequent complication of premature newborns, particularly very low birth-weight babies (<1500 g). Undoubtedly multiple mechanisms contribute to the adverse outcomes associated with BPD but oxidative stress is one causative factor. In this issue of Free Radical Biology and Medicine, Lavoie et al. describe the increased peroxide generation when the multivitamin solution used for nutritional support, total parenteral nutrition (TPN), is exposed to ambient light. Because the premature newborn has limited antioxidant capacity, this increased oxidative burden from the TPN becomes increasingly significant. Infusion of this light-exposed solution in a newborn guinea pig decreased lung tissue vitamin C but not vitamin E. When the multivitamin and lipid solutions were mixed and then exposed to light, alveolarization of the developing lung was decreased. This study by Lavoie et al. highlights simple measures that can potentially decrease the oxidant burden delivered to this vulnerable population and improve alveolarization.     

Antioxidants in patients receiving total parenteral nutrition after gastrointestinal cancer surgery

Total parenteral nutrition (TPN) is essential for patients with postoperative impairing gastrointestinal function who are unable to receive and absorb oral/enteral feeding for at least 7 days. Oxidative stress plays a major role in the ethiopathogenesis of cancers. In this study, total antioxidant status (TAS), glutathione peroxidase (GPx), superoxide dismutase, malondialdehyde and ascorbic acid were studied in patients operated because of small intestine, colorectal or pancreatic cancer and subsequently receiving TPN in comparison with patients receiving standard nutrition after the operation. TAS level and GPx activity were decreased in patients with small intestine cancer but did not differ in patients with colorectal and pancreatic cancer before and after surgery. In all patient groups receiving TPN, superoxide dismutase activity after the surgery was kept at the same level as before. On the fifth day after the surgery, malondialdehyde concentration in each group was restored to the value observed before surgery. On the fifth day of TPN treatment, ascorbic acid concentration was increased in every group of patients. TPN applied during the postoperative period alleviates oxidative stress resulting from surgery. In the case of small intestine cancer, the addition of vitamins and antioxidants to the nutrition mixture seems to result in depletion of antioxidant enzymes' activities.     

早期肠内营养和肠外营养对ICU中重症肺炎患者预后的影响

目的:研究早期肠内和肠外营养对ICU中重症肺炎患者预后的影响。方法:选取2013年1月-2014年1月我院重症医学科60例重症肺炎患者随机分为肠内营养组30例(enteral nutrition,EN组)和完全肠外营养支持组30例(total parenteral nutrition,TPN组),经过营养支持治疗后,将两组的免疫、营养以及有创机械通气的时间等指标进行比较。结果:肠内营养组与肠外营养组对比发现,在第5天、第10天EN组血清免疫球蛋白和T细胞亚群细胞数显著升高(P0.05);血红蛋白(HGB)、白蛋白(ALB)和血清前白蛋白(PAB)明显升高(P0.05);有创机械通气时间缩短(P0.05),差异具有统计学意义。结论:ICU中重症肺炎应选择肠内营养支持方式,肠内营养能有效的改善营养状态,并能改善患者的免疫功能,减少有创机械通气时间。     

Arginine deficiency in preterm infants: biochemical mechanisms and nutritional implications

Arginine, an amino acid that is nutritionally essential for the fetus and neonate, is crucial for ammonia detoxification and the synthesis of molecules with enormous importance (including creatine, nitric oxide, and polyamines). A significant nutritional problem in preterm infants is a severe deficiency of arginine (hypoargininemia), which results in hyperammonemia, as well as cardiovascular, pulmonary, neurological, and intestinal dysfunction. Arginine deficiency may contribute to the high rate of infant morbidity and mortality associated with premature births. Although hypoargininemia in preterm infants has been recognized for more than 30 years, it continues to occur in neonatal intensive care units in the United States and worldwide. On the basis of recent findings, we propose that intestinal citrulline and arginine synthesis (the major endogenous source of arginine) is limited in preterm neonates owing to the limited expression of the genes for key enzymes (e.g., pyrroline-5-carboxylate synthase, argininosuccinate synthase and lyase), thereby contributing to hypoargininemia. Because premature births in humans occur before the normal perinatal surge of cortisol (an inducer of the expression of key arginine-synthetic enzymes), its administration may be a useful tool to advance the maturation of intestinal arginine synthesis in preterm neonates. Additional benefits of cortisol treatment may include the following: 1) allowing early introduction of enteral feeding to preterm infants, which is critical for intestinal synthesis of citrulline, arginine, and polyamines as well as for intestinal motility, integrity, and growth; and 2) shortening the expensive stay of preterm infants in hospitals as a result of accelerated organ maturation and the restoration of full enteral feeding. Further studies of fetal and neonatal arginine metabolism will continue to advance our understanding of the mechanisms responsible for the survival and growth of preterm infants. This new knowledge will be beneficial for designing the next generation of enteral and parenteral amino acid solutions to optimize nutrition and health in this compromised population.