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Josef Neu

Publications and source records attributed to Josef Neu.

35 records · Page 2Linked to original sources
PubMed2004

Glutamine decreases lipopolysaccharide-induced intestinal inflammation in infant rats.

Using a gastrostomy-fed (GF) rat infant "pup-in-a-cup" model, the effects of protein deprivation and supplemental glutamine (Gln) and glutamate (Glu) were examined to test the hypothesis that Gln decreases the proinflammatory response induced by LPS in the developing infant rat small intestine. Four groups of 6- to 7-day-old pups were fed a rat milk substitute (RMS), one providing 100% and three providing 25% of normal protein intake for another 6 days. Two of the 25% protein-fed groups received supplemental Gln or Glu. GF and LPS treatment blunted body growth and intestinal villus height and increased intestinal cytokine-induced neutrophil chemoattractant (CINC) mRNA in the protein-deprived, non-Gln-treated group compared with mother-fed pups (P < 0.05). Gln blunted intestinal CINC mRNA (P < 0.05), but Glu did not. Intestinal CINC peptide in the LPS-treated pups provided 100 and 25% protein was elevated approximately 13-fold compared with the mother-reared pups (P < 0.001). Gln and Glu decreased intestinal CINC peptide by 73 and 80%, respectively. GF, LPS-treated pups also had a higher level of plasma CINC peptide (P < 0.05). Gln but not Glu decreased plasma CINC peptide (P < 0.05). An approximate sixfold elevation of intestinal MPO activity in the GF, LPS-treated rats was decreased by Gln and Glu by 92% (P < 0.001) and 54% (P < 0.05), respectively. Intestinal and plasma TNF-alpha were increased in GF, LPS-treated pups (P < 0.01), and Gln and Glu both blunted this increase (P < 0.05) in the intestine but not in the plasma. The results indicate that Gln decreases the LPS-induced inflammatory response in infant rat intestine under different conditions of protein intake.

Animals↗
PubMed2004

Substitutes for glutamine in proliferation of rat intestinal epithelial cells.

OBJECTIVES: Glutamine (Gln) is important for intestinal epithelial proliferation. The purpose of this study was to determine whether glutamate (Glu), a mixture of nucleotide monophosphates, arginine, or glucosamine could support proliferation of rat intestinal crypt cells (IEC-6) in the absence of Gln. METHODS: Glu with added ammonia acetate, glucosamine, arginine, and nucleotide monophosphates were tested at concentrations that were isonitrogenous with respect to Gln. To determine whether de novo synthesis of Gln was affected by these nutrients, a duplicate set of treatment groups was also tested with 1.0 mM/L of methionine sulfoximine, an inhibitor of Gln synthetase. RESULTS: Gln + methionine sulfoximine-treated cells showed suboptimal proliferation below 0.6 mM/L but normal proliferation between 0.6 and 4.0 mM/L of Gln. In the absence of exogenous Gln, isonitrogenous concentrations of Glu, glucosamine, arginine, or nucleotide monophosphates yielded similar proliferation as Gln. Cells treated with Glu, glucosamine, arginine, or nucleotide monophosphate mixture showed a decrease in proliferation compared with cells treated with Gln across all treatment doses (P < 0.03). CONCLUSIONS: The importance of these results is that, in the presence of active Gln synthetase, these nutrients can maintain intestinal epithelial proliferation similar to that observed with Gln.

Acetates↗
PubMed2004

Effects of protein deprivation on growth and small intestine morphology are not improved by glutamine or glutamate in gastrostomy-fed rat pups.

OBJECTIVES: Critically ill neonates often have their enteral intake severely limited shortly after birth. Whether glutamine (Gln) or glutamate (Glu) can preserve intestinal structure and function in the neonate undergoing limited enteral feeding is not clear. We hypothesize that Gln and Glu can similarly preserve intestinal structure in the developing small intestine of infant rats fed a low protein diet. METHODS: Using a gastrostomy-fed "pup-in-a-cup" rat model, the effects of Gln and Glu on the developing rat small intestine were examined. Four groups of 6- to 7-day-old pups were fed rat milk substitute (RMS) via gastrostomy tube. One group was provided 100% and three were provided 25% of the protein normally received from their mothers. Two of the groups fed 25% protein received additional Gln or Glu for 6 days. RESULTS: Pups receiving the 100% protein RMS were larger than pups receiving the 25% protein RMS with or without Gln/Glu supplementation (P < 0.001). Average villus height (P < 0.01) and area (P < 0.01) were greater in pups receiving 100% protein RMS than in pups given 25% protein RMS formula. There was no significant difference among the groups in mucosal maltase or alkaline phosphatase activities. Tight junction protein claudin-1 was significantly higher in the group fed 100% protein RMS diet, while occludin did not differ among the 4 groups. Neither Gln nor Glu increased claudin-1 or occludin in rats fed 25% protein. CONCLUSIONS: These results suggest that neither Gln nor Glu supplementation can substitute effectively for whole protein in the developing rat small intestine for the outcomes that were evaluated.

Alkaline Phosphatase↗
PubMed2003

Immunonutrients and neonates.

UNLABELLED: The gastrointestinal tract is the largest surface area of the body and the primary site for microorganisms, foreign antigens and toxins to gain entry to the host's internal milieu. The use of enteral feedings enriched with immune-enhancing ingredients is attracting considerable interest because there is increasing application of enteral feeding and appreciation of the role of the gut in the development of infection and of multiple organ failure in critically ill patients. CONCLUSION: in this review, we will discuss nutrients, such as glutamine, arginine, omega 3 fatty acids, nucleotides, probiotics, and lactoferrin, and how they might be used as immunonutrients in neonatal clinics.

Adjuvants, Immunologic↗
PubMed2003

Glutamine supports recovery from loss of transepithelial resistance and increase of permeability induced by media change in Caco-2 cells.

Recent evidence suggests that the conditionally essential amino acid glutamine is important for intestinal barrier function. However, the mechanism remains undefined. To determine the effects of glutamine on permeability of intestinal epithelial cell monolayers, Caco-2 cells were grown on membrane filters and exposed to 4 mmol/L sodium butyrate in order to rapidly achieve high levels of alkaline phosphatase and high transepithelial resistance as seen in functionally mature enterocytes. A standard method of medium exchange consisting of removal and replacement resulted in a catastrophic loss of transepithelial resistance and increase of mannitol and dextran fluxes that required 2-4 hrs and protein synthesis to recover. The effect was attributed to exposure of the upper monolayer surface to atmosphere and could be avoided by refeeding by incremental perfusion. Spontaneously-differentiated Caco-2 monolayers were resistant to this stress. This novel stress test was employed as a sensitive assay for the requirement of glutamine for monolayer transepithelial resistance and mannitol permeability. Pre-stress glutamine availability was more important than Gln-availability during the recovery phase. Thus the transepithelial resistance and permeability of butyrate-induced monolayers is dynamically-regulated in response to atmospheric exposure, by a mechanism that depends on threshold levels of glutamine availability.

Alkaline Phosphatase↗
PubMed2003

Glutamine decreases lipopolysaccharide-induced IL-8 production in Caco-2 cells through a non-NF-kappaB p50 mechanism.

Glutamine (Gln) supplementation has been shown to decrease production of pro-inflammatory cytokines by the human intestinal mucosa. The mechanism of this is poorly understood. We hypothesize that Gln down-regulates lipopolysaccharide (LPS)-stimulated pro-inflammatory cytokine production in Caco-2 cells by nuclear factor-kappa B (NF-kappaB). Caco-2 cells were incubated with different concentrations of Gln with or without methionine sulfoximine (MS, an inhibitor of glutamine synthetase) before stimulation with LPS. IL-6, IL-8, IL-10 and TNF-alpha protein and mRNA level were determined. NF-kappaB translocation was determined using an ELISA-based kit. IL-8 was the only detectable cytokine/chemokine. The largest amount of IL-8 was secreted by cells in the presence of MS with no Gln in the medium after exposure to LPS. LPS increased IL-8 production, peaking 10h after LPS administration. The addition of Gln (0.5 or 5.0mM) decreased IL-8 peptide and mRNA expression. LPS increased NF-kappaB nuclear translocation in the presence or absence of MS. Neither Gln nor MS altered NF-kappaB nuclear translocation. These results indicate that the lack of glutamine increases IL-8 production by Caco-2 cells after LPS stimulation. However, the glutamine-mediated decrease in LPS-stimulated IL-8 production is not associated with NF-kappaB p50 nuclear binding.

Caco-2 Cells↗
PubMed2003

Nutrition in the neonatal intensive care unit: how do we reduce the incidence of extrauterine growth restriction?

Extrauterine growth restriction is a major clinical problem for prematurely born neonates, especially critically ill preterm neonates, and malnutrition in the neonatal intensive-care unit remains common. There are numerous perceived risks to initiation of adequate nutritional support. How many of these factors pose a real risk to health outcomes is less clear. Current nutritional support does not prevent extrauterine growth restriction and the consequences of malnutrition are both acute and delayed. Our clinical approach to providing nutritional support impacts neonatal morbidity and long-term neuro developmental outcomes. While more and better evidence is needed to help guide best practices, this gap should not prevent neonatologists from using the observations in this review to improve their current practice. There is evidence that changes in nutritional support can have a positive influence on growth. These include early administration of intravenous amino acids and lipids, minimal enteral nutrition, and supplemented formula and human milk. Simply recognizing the degree of growth failure by monitoring weight and focusing on the accruing deficit should encourage clinicians to increase nutritional support to enhance recovery growth. Continued research is needed to define the efficiency of early feeding, more rapid advancements in nutritional support, protein needs, the optimal composition of breast-milk supplements, the etiology of necrotizing enterocolitis, and perhaps most importantly, the health consequences of extrauterine growth restriction.

Growth Disorders↗
PubMed2003

Enteral glutamine supplementation and morbidity in low birth weight infants.

OBJECTIVE: To determine if glutamine-supplemented enteral nutrition decreased the incidence of nosocomial sepsis in neonates. METHODS: In a multicenter (n = 20) clinical trial, we randomly allocated infants (n = 649) with birth weight between 500 and 1250 g, who were <7 days of age, and had no major anomalies to receive enteral glutamine supplementation (0.3 g/kg/day) or sterile water (placebo) for the first 28 days. The primary outcome variable was the number of infants who had blood culture-proven nosocomial sepsis between 7 days' and 36 weeks' postmenstrual age. RESULTS: Infants were assigned to placebo (n = 335) or to glutamine supplementation (n = 314). Neonates assigned to glutamine were similar to those assigned placebo for demographic characteristics and nutritional support during the first week. There was no difference in the occurrence of culture-proven nosocomial sepsis (33.7% vs 30.9%) or suspected sepsis (51.6% vs 47.1%) between the placebo and glutamine groups; however, neonates treated with glutamine less often had gastrointestinal dysfunction (7.5% vs 2.5%, P <.01) and severe neurologic sequelae (15.1% vs 10.4%, P =.08). CONCLUSIONS: At a dose of 0.3 g/kg/day, enteral glutamine does not appear to reduce nosocomial sepsis in premature neonates.

Adolescent↗
PubMed2003

Glutamine and barrier function in cultured Caco-2 epithelial cell monolayers.

Dietary glutamine (Gln) has been shown to be important for maintenance of the intestinal barrier. To investigate the role of the epithelium in this Gln dependence, Caco-2 cells were raised on semipermeable membranes under conditions that model different regions of the crypt and villus. Gln availability was controlled by addition to the medium and treatment with methionine sulfoximine to inhibit Gln synthetase (GS). Barrier function was assayed by measuring transepithelial electrical resistance and fluxes of [(14)C]mannitol and fluorescein isothiocyanate-dextran. The barrier function of these monolayers was found to require the Gln provided either in the medium at the apical or basal surface or via GS. However, the barrier was no more sensitive to Gln deprivation than it was to accumulation or maintenance of total protein. These results suggest that the in vivo dependence of the gut mucosal barrier on Gln likely involves roles separate from maintenance of the epithelial barrier per se.

Caco-2 Cells↗
PubMed2002

Update on host defense and immunonutrients.

Neonatal intensive care in the past three decades has provided exciting modalities for improving the survival of critically ill neonates. There remains a great need for improving the quality of life for these survivors. In this article, the role the developing GI tract and its microenvironment play in the well-being of the neonate has been emphasized. Future therapies based on manipulation of the GI tract and its microenvironment by functional foods, immunonutrients, or pharmacologic agents may have effects not only during the neonatal period, but also throughout the individual's entire life.

Arginine↗
PubMed2002

Indomethacin, dexamethasone, and intestinal damage in infant rats.

BACKGROUND: Indomethacin is commonly used in the Neonatal Intensive Care Unit to induce closure of the patent ductus arteriosus and to prevent intraventricular hemorrhage. It is known that indomethacin causes intestinal ulceration in adults, but its effect in infants is less clear. In a preliminary experiment, it was found that the administration of 10 mg/kg/d of indomethacin, a dose that damages the adult rat intestine, had no detrimental effects on newborn suckling rats whereas dexamethasone at 0.25 mg/kg/d caused significant growth failure and villous blunting. It was then hypothesized that the lack of intestinal damage with indomethacin in infants was related to protection given by mother's milk. METHODS: Subsequent experiments were performed wherein 10 mg/kg/d of indomethacin was provided to infant mother-reared, infant artificially fed, and adult rats. The expression of intestinal cyclooxygenases in the prostaglandin synthetic pathway of control rats was examined to initiate an exploration into a mechanism for the developmental response to indomethacin. RESULTS: Mother-reared and artificially fed infant rats demonstrated resistance to the ulcerogenic effects of indomethacin, in contrast to the adults. A differential presence of cyclooxygenase-1 and cyclooxygenase-2 was not distinctly seen between infancy and adulthood. CONCLUSIONS: The results indicate that a varying response to the damaging effects of indomethacin on the intestine occurs during development with the infant being less susceptible than the adult. This differed from the effects of dexamethasone administration, which caused significant intestinal atrophy in the infant rats. The intestinal protection to the effects of indomethacin in infants is not dependent on mother's milk or a developmental difference in the prostaglandin biosynthetic pathway.

Age Factors↗
PubMed2002

Glutamine: clinical applications and mechanisms of action.

Supplementation of the conditionally essential amino acid glutamine may be beneficial for individuals who are highly stressed and have minimal energy and protein reserves. This includes elderly individuals, postoperative patients, individuals with cancer and very low birthweight infants. Individuals who are undergoing treatment with catabolic glucocorticoids may also benefit. Unfortunately, confusion exists as to situations in which glutamine may be beneficial because a clearly defined "glutamine deficiency syndrome" has not been described as for some other nutrients. In this review, we will discuss how glutamine affects protein metabolism under certain stressful conditions, how it affects intestinal mucosal integrity and how this might relate to sepsis and systemic inflammation. We will also discuss nutrients that are closely related to glutamine such as glutamate, nucleotides, arginine, glucosamines, and ornithine alpha-ketoglutarate and how and why they might be used as substitutes for glutamine.

Critical Illness↗
PubMed2002

Glutamine supplementation and deprivation: effect on artificially reared rat small intestinal morphology.

The mechanisms of how glutamine benefits critically ill patients have not been established. The purpose of this study was to determine the effects of dietary and endogenously produced glutamine on small intestinal morphology using light and transmission electron microscopy in artificially reared rat pups. It was hypothesized that deprivation of dietary glutamine leads to intestinal disease that is exacerbated by inhibition of glutamine synthetase by methionine sulfoximine (MS). Rat pups were placed into five different test groups: The first was a reference group that was reared by their mother. The other four groups were reared artificially and received a 10% Travasol amino acid solution at 5 g/kg per day, which does not contain glutamine, added to a mixture containing carbohydrates, lipids, and vitamins. This dose was chosen because it represents an approximation of the amount of glutamine these rats would be receiving in a normal rat diet (approximately 40 g/kg per day total protein, 10 to 15% of which is glutamine + glutamate). The glutamine was manipulated by adding glutamine (Q) or MS or both. The four groups were as follows: MS-Q-, MS-Q+, MS+Q-, and MS+Q+. Light microscopy revealed the greatest blunting of villus height in the ileum of rats from the MS+Q- group when compared with the MS-Q+ group (123 +/- 48.9 micro m versus 207 +/- 36 microm, p < 0.05). The other two groups exhibited intermediate villus heights, but all were shorter than the villi from the mother-reared animals. The number of villi per unit length of bowel was also lowest in the animals that were treated with MS and not provided with dietary glutamine. Transmission electron microscopy demonstrated breakdown of the epithelial junctions in the glutamine-deprived and glutamine synthetase-inhibited intestines. Glutamine-deprived animals also displayed sloughing of microvilli, decreased actin cores, and degeneration of the terminal web. In summary, these studies support the hypothesis that glutamine is involved with maintenance of intestinal epithelial integrity.

Amino Acids↗