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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mechanisms of nutrient alteration of hepatic protein synthesis during sepsis are unclear. In vitro, arginine downregulates endotoxin-stimulated hepatocyte protein synthesis but in vivo effects are unknown. This study evaluated the effects of supplemental arginine or glycine on fibrinogen (acute-phase protein), histone, albumin, and liver protein synthesis after Gram-negative sepsis in the rat. Adult rats (225 g, n = 36) were randomized to receive isonitrogenous isocaloric total parenteral nutrition supplemented with 264 mg of N per kilogram per day as either arginine or glycine. On day 5, each group was further randomized to control or sepsis. Sepsis was induced by injection of 8 x 10(7) Escherichia coli per 100 g body weight, and then a continuous infusion of [1-14C]leucine was started. The rats were sacrificed 4 hours later. The fractional protein synthesis rates (percent per day) of histone, fibrinogen, albumin, and liver were determined. Supplemental arginine led to significantly increased histone (p less than 0.05, analysis of variance) and fibrinogen (p less than 0.01, analysis of variance) synthesis in the septic rats compared with all other groups. Histone and albumin synthesis were also significantly increased (p less than 0.05) in the arginine-supplemented control group compared with the glycine-supplemented control group. Arginine supplementation during sepsis significantly increased (p less than 0.05) albumin and liver protein synthesis compared with controls. Histones which are involved in DNA synthesis and are rich in arginine may play a role in the host response to stress and sepsis. These in vivo results appear to contradict hepatocyte-Kupffer cell coculture studies perhaps because of the hormonal and cytokine responses to nutrient substrate and acute septicemia.
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PMID:Harry M. Vars Research Award. Arginine supplementation improves histone and acute-phase protein synthesis during gram-negative sepsis in the rat. 171 54

Hypermetabolism and multiple organ failure syndrome (MOFS) after trauma, surgery, or sepsis is associated with accelerated catabolism, the rapid onset of malnutrition, and immune system failure. Current nutritional support, enteral or parenteral, can achieve an acceptable nutritional response but appears unable to improve immune function. Nutrients such as arginine, refined menhaden oil, and RNA have been found to have immune-stimulating properties. This randomized blind prospective trial compared two nutritionally complete enteral formulas, one supplemented with arginine, menhaden oil, and RNA, on the disease-specific effects of anergy and suppression of in vitro tests of immune function in intensive-care patients and the nutritional outcome of nitrogen balance. After 7-10 days of enteral nutrition in patients with persistent sepsis syndrome, both formulas were associated with the achievement of net nitrogen retention and improved visceral protein status but with nonresolution of anergy. However, the supplemented formula was associated with marked stimulation of in vitro lymphocyte proliferative responses and a significant reduction in 3-methylhistidine excretion. Six and 12-mo follow-up data demonstrated no long-term effects. Nutrients targeted to effect the disease-induced in vitro suppression of immune function in MOFS appear to achieve that end independent of the nutritional outcome of nitrogen balance and without adverse clinical outcome.
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PMID:Improvement in immune function in ICU patients by enteral nutrition supplemented with arginine, RNA, and menhaden oil is independent of nitrogen balance. 172 41

The response to injury and infection can be viewed as a mobilization of body protein, fat, and carbohydrate stores to ensure normal or above-normal circulating levels of substrate in the absence of dietary intake. The situation does not readily yield to nutritional manipulation, and inappropriate nutritional support can cause additional stress. Artificial nutrition is mainly a form of nutrient administration and not nutrient utilization. Modulation of neurohumoral and wound responses to trauma due to starvation and refeeding has not been delineated. The provision of adequate substrates alone does not necessarily guarantee their efficient use in metabolism. With a clear knowledge of the role of cellular mediators in the pathophysiology of disease, it may be possible to develop more rational therapeutic approaches during critical illness. Determination of appropriate and optimal substrate support through parenteral and enteral nutrition remains of great clinical importance. The clinical application of branched-chain amino acids, dispensable amino acids, acetylated amino acids, dipeptides or tripeptides, cysteine, glutamine, and arginine has been explored in recent years. The idea that lipids are deleterious in sepsis and organ failure should be revised and documented, and recent studies suggest that fish oils as a lipid source may also favorably affect immune responses. Under stressful conditions, total parenteral nutrition can require large amounts of energy at a time when there are marked disturbances in glucose utilization. In this area, the use of nonglucose carbohydrates or oligosaccharides can be appropriate, despite the lack of broad acceptance. Existing conventional substrates should be studied beyond mere provision of energy and metabolic pathway support.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nutritional and metabolic support: converging concepts. 180 4

Sepsis and organ failure produce profound metabolic changes that contribute to hepatic and musculoskeletal failure. When multiple organ failure develops, the mortality rate is high, and therapy is unlikely to be effective unless the causative process (e.g., infection, low cardiac output) can be eliminated. Thus, the prevention of multiple organ failure and the prevention or early treatment of infection are paramount. Organ and nutritional support to prevent complications is necessary. The gastrointestinal tract should be used for nutrition whenever possible with a blenderized regular diet with fiber, glutamine, and short-chain fatty acids to protect and preserve the gut. If parenteral nutrition is necessary, special solutions may be necessary for the liver, kidneys, or lungs. If not, protein with 45% branched-chain amino acid, medium- and short-chain triglycerides, glutamine supplementation, and carbohydrates seem best. Other substances are being evaluated that may be helpful in nutrition and organ support, including arginine, xylitol, growth hormone, and anabolic steroids. Multiple organ failure should be prevented, if at all possible, by stopping or controlling the injury, removing as much necrotic tissue as possible, improving blood flow and oxygen consumption, supporting metabolism, and preventing infection or treating it early and adequately. Nutritional support plays a key role in preventing metabolic failure.
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PMID:Nutrition and metabolism in sepsis and multisystem organ failure. 190 43

Concentrations of amino acids in the plasma of 13 neonatal foals with septicemia were compared with the concentrations of amino acids in the plasma of 13 age-matched neonatal foals without septicemia. Analysis of the results revealed significantly lower concentrations of arginine, citrulline, isoleucine, proline, threonine, and valine in the plasma of foals with septicemia. The ratio of the plasma concentrations of the branched chain amino acids (isoleucine, leucine, and valine) to the aromatic amino acids (phenylalanine and tyrosine), was also significantly lower in the foals with septicemia. In addition, the concentrations of alanine, glycine, and phenylalanine were significantly higher in the plasma of foals with septicemia. Therefore, neonatal foals with septicemia had significant differences in the concentrations of several amino acids in their plasma, compared with concentrations from healthy foals. These differences were compatible with protein calorie inadequacy and may be related to an alteration in the intake, production, use, or clearance of amino acids from the plasma pool in sepsis.
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PMID:Concentrations of amino acids in the plasma of neonatal foals with septicemia. 190 45

Critically ill patients have increased rates of sepsis partly due to a down-regulated immune system. Nutrients may modulate the immune system. The following studies were performed to determine whether arginine is one of these "essential" nutrients for the immune system. Thirty-two male Sprague-Dawley rats (weighing 175 g) were divided into two groups that were pair-fed with either an elemental, arginine-supplemented enteral diet, or the same diet with arginine removed and replaced with glycine. Both diets were isocaloric, isoosmolar, and isonitrogenous. After 6 days on the diet, animals underwent testing. There were no significant differences between the arginine-supplemented and the arginine-free diet groups in blood glucose or hematocrit. The arginine-supplemented animals had higher serum albumin (4.1 +/- 0.1 mg/dL v 3.6 +/- 0.1 mg/dL; P = .035) and serum protein levels (5.2 +/- 0.1 mg/dL v 4.3 +/- 0.1 mg/dL; P = .041); and had higher thymus gland (0.53 +/- 0.03 g v 0.44 +/- 0.02 g; P less than .0001) and spleen weights (0.66 +/- 0.01 g v 0.57 +/- 0.01 g; P less than .01). Daily total urinary nitrogen excretion, nitrogen balance, and weight gain showed a tendency for the arginine-supplemented animals to retain more of their nitrogen calories. There was no difference in the amount of hydroxyproline (OHP) found in the wound cylinders of either group (both 25.6 micrograms OHP/cm polytetrafluoroethylene) but the arginine-supplemented group's wounds had greater wound bursting strengths (429 +/- 3 g/cm v 350 +/- 7 g/cm; P = .044).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of an arginine-free enteral diet on wound healing and immune function in the postsurgical rat. 191 87

Two similar cohorts of low birth weight infants whose size was appropriate for gestational age randomly received either aztreonam-arginine plus ampicillin (n = 15) or gentamicin plus ampicillin (n = 15) for empiric treatment of neonatal sepsis. The regimens were infused together with glucose at greater than 5 mg/kg per minute, and immediate (4 hours) and cumulative (3 days) effects were assessed. Serum arginine and insulin values rose immediately after administration of aztreonam (containing 0.15 mmol of arginine per kilogram), but there were no changes in the gentamicin-treated cohort; no differences occurred in either cohort in serum concentrations of glucose, ammonia, potassium, creatinine, and bilirubin. After 3 days of antibiotic therapy (n = 13), the baseline serum arginine concentration was almost twice as high in the aztreonam group and showed a similar further rise and fall during the 4 hours after infusion; arginine urinary fractional excretion (normalized to creatinine clearance) decreased in the gentamicin group. The indirect bilirubin concentration rose more (p less than 0.001) in the aztreonam-treated infants (5.1 to 11.5 mg/dl (87 to 196 mumol/L] than in the gentamicin-treated infants (5.5 to 8.1 mg/dl (94 to 138 mumol/L)). Thus a modest differential bilirubin response and modestly elevated baseline serum arginine level occurred after the 3-day low-arginine doses of this study; serum ammonia and glucose concentrations were not affected. Aztreonam-arginine in neonates was well tolerated metabolically, and we believe that it can be used safely in conjunction with attention to glucose and bilirubin metabolism.
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PMID:Metabolic tolerance to arginine: implications for the safe use of arginine salt-aztreonam combination in the neonatal period. 204 Sep 35

To evaluate the efficacy of supplemental arginine with nutritional support in the presence of sepsis, eighty-eight gastrostomized female Hartley guinea pigs were implanted with osmotic pumps effusing an Eschericia coli/Staphylococcus aureus mixture. Animals were randomized and infused for two weeks with isocaloric and isovolumetric diets containing 0%, 2%, 4%, or 6% supplemental arginine as arginine hydrochloride. Survival was 12/22 (54%) in 0%, 9/22 (41%) in 2% and 4%, and 2/22 (9%) in 6%. Analysis by chi-square test of independence was significant (p = 0.0141) with 6% survival lower than the others. Median survival was 11 days in 0%, 8 days in 2% and 6%, and 9 days in 4%. Median survival was longer in 0% than in 2% or 6% (Kruskal-Wallis ANOVA: p = 0.02). Nitrogen balance was significantly lower in 6% compared to 0% on days 2 through 10, and lower than 2% and 4% on days 6 and 9. Nitrogen balance was higher in 0% than in 2% on days 4, 6, 10, and 13. Serum albumin and C3 were lower in all experimental groups than normal controls (ANOVA: p = 0.01). Comparison of liver, spleen, adrenals, gastrocnemius, and carcass weights, cell-mediated immunity as determined by contact sensitivity to DNFB, and transferrin showed no significant differences. There was a positive dose-response effect seen amongst the experimental groups for the amino acids arginine, ornithine, and citrulline in relation to the amount of supplemental arginine. This study suggests that dietary arginine supplementation does not enhance survival in a guinea pig model of established peritonitis.
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PMID:Arginine supplementation and its effect on established peritonitis in guinea pigs. 211 35

The etiology and mechanisms by which severe trauma or sepsis induce hepatic failure are unknown. Previously we showed that Kupffer cells (KC), the fixed macrophages of the liver, induce a profound decrease in hepatocyte (HC) total-protein synthesis when exposed to endotoxin. Furthermore we demonstrated that endotoxin-activated KCs induce these changes in HC protein synthesis through the induction of a novel L-arginine-dependent biochemical pathway within the HC. In this pathway, the guanido nitrogen of L-arginine is converted to the highly reactive molecule nitric oxide (NO.). To identify the KC factors that act as signals for induction of HC NO. biosynthesis, recombinant cytokines were added to HC cultures and HC nitrogen oxide production and protein synthesis levels were determined. We found that no single cytokine, but rather a specific combination of tumor necrosis factor, interleukin-1, interferon-gamma, and endotoxin, were required for maximal induction of HC nitrogen oxide production. This specific combination of cytokines induced a 248.8 +/- 26.0 mumol/L (micromolar) increase in HC nitrogen oxide production and simultaneously inhibited HC total protein synthesis by 36.1% +/- 3.1%. These data demonstrate that multiple cytokines, produced by endotoxin-activated KC, induce the production of NO. within HC, which in turn leads to the inhibition of HC total-protein synthesis.
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PMID:Multiple cytokines are required to induce hepatocyte nitric oxide production and inhibit total protein synthesis. 212 Nov 10

Nitric oxide (NO.) is a short-lived intermediate in a biochemical pathway where L-arginine is converted to L-citrulline and nitrite/nitrate (NO2-/NO3-). This highly reactive molecule is the biologically active component of this inducible pathway in macrophages. Using a rat Kupffer cell:hepatocyte (KC:HC) coculture model, we have previously shown that this combination of cells produces large quantities of both citrulline and NO2-/NO3- if exposed to lipopolysaccharides (LPS) but we did not determine whether nitric oxide was produced or released. We had also shown that this L-arginine metabolism was associated with a profound decrease in total protein synthesis. In these experiments, we show that KC:HC cocultures release nitric oxide into the culture supernatant if exposed to LPS. NO. production by these cells requires L-arginine and is inhibited by NG-mono-methyl-L-arginine. In addition, the time course for NO. release by KC:HC cocultures parallels the previously reported time course for NO2-/NO3- synthesis and the decrease in protein synthesis, supporting the hypothesis that NO. is the reactive nitrogen intermediate of the pathway responsible for this inhibition of protein synthesis. Finally, we show that KC:HC cocultures release more NO. than KC alone in response to LPS, and we propose that the combination of KC and HC acts as a functional unit capable of generating large amounts of NO. from L-arginine in gram-negative sepsis.
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PMID:Kupffer cell:hepatocyte cocultures release nitric oxide in response to bacterial endotoxin. 218 13


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