Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The branched-chain amino acids (BCAAs; valine, isoleucine, and leucine) are the major nitrogen source for glutamine and alanine synthesis in muscle. Synthesis of glutamine, alanine, and BCAA use is activated in critical illnesses such as in sepsis, cancer, and trauma. The use of glutamine often exceeds its synthesis, resulting in the lack of glutamine in plasma and tissues. In critical illness, resynthesis of BCAA from branched-chain keto acids is activated, particularly in hepatic tissue. The BCAA released to circulation may be used for protein synthesis or synthesis of alanine and glutamine. Glutamine and/or alanine infusion has an inhibitory effect on the breakdown of body proteins and decreases BCAA catabolism in postabsorptive control, endotoxemic, and irradiated rats. Decreased protein breakdown also was observed when glutamine synthesis was activated by ammonia infusion. In conclusion some favorable effects of BCAA supply can be explained by its role in the synthesis of glutamine and some positive effects of glutamine exogenous supply can be explained by its effect on metabolism of BCAA.
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PMID:Relation between glutamine, branched-chain amino acids, and protein metabolism. 1184 43

Glutamine has beneficial effects on enterocytes and the immune system in sepsis, but its effects on hepatic metabolism remain unknown. The aim of the present study was to determine the effects of glutamine on hepatocyte energy metabolism under conditions of neonatal endotoxaemia. Suckling Wistar rats were injected intraperitoneally with 200 microg/kg lipopolysaccharide. Oxygen consumption was measured polarographically in hepatocytes respiring on either palmitate (0.5 mM) or palmitate plus glutamine (10 mM). Total hepatocyte oxygen consumption was similar in hepatocytes from control and endotoxic rats, but this was due to a decrease in intramitochondrial and an increase in extramitochondrial oxygen consumption in the cells from endotoxic animals. The addition of glutamine to hepatocytes from endotoxic rats restored intramitochondrial oxygen consumption to control levels. Although glutamine did not reverse the inhibition of the thermogenic proton leak observed in endotoxaemia, it significantly increased oxygen consumption due to mitochondrial ATP synthesis (P=0.03). Glutamine significantly increased the hepatocyte ATP/ADP ratio (P=0.02 compared with hepatocytes from endotoxic rats). Electron microscopy revealed morphological damage to the mitochondria of hepatocytes from endotoxic rats, and a return to a normal appearance with the addition of glutamine. We conclude that glutamine reverses the inhibition of mitochondrial metabolism that is observed in endotoxaemia. The effect is primarily at the level of ATP synthesis.
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PMID:Hepatocyte mitochondrial metabolism is inhibited in neonatal rat endotoxaemia: effects of glutamine. 1186 75

Critically ill patients on intensive care units are at an increased risk of sepsis, which is a major cause of mortality in these patients. Recent evidence suggests that impairment of the functioning of the immune system contributes to the development of sepsis in such patients. In particular, monocytes show reduced expression of HLA-DR antigen, associated with impaired antigen presenting capability and decreased phagocytic activity; lymphocytes show decreased proliferation in response to mitogens and T-helper cells show a shift in the Th1/Th2 ratio consistent with impaired immunity. The amino acid glutamine becomes conditionally essential in the critically ill, yet such patients frequently have a marked deficiency of glutamine; the reasons for this are still unclear. Glutamine is required by the cells of the immune system both as a primary fuel and as a carbon and nitrogen donor for nucleotide precursor synthesis. In vivo studies have demonstrated that glutamine is essential for optimal immune cell functioning for monocytes, lymphocytes and neutrophils. A number of trials of patients fed by the enteral or parenteral route have shown improved infectious morbidity when supplemented with glutamine. However, the exact mechanism of glutamine action in these patients remains to be determined.
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PMID:Glutamine: essential for immune nutrition in the critically ill. 1189 53

An increasing number of clinical investigations have focused on supplementation of specialized enteral and parenteral nutrition with the amino acid glutamine. This interest derives from strong evidence in animal models and emerging clinical data on the efficacy of glutamine administration following chemotherapy, trauma, sepsis and other catabolic conditions. Glutamine has protein-anabolic effects in stressed patients and, among many key metabolic functions, is used as a major fuel/substrate by cells of the gastrointestinal epithelium and the immune system. These effects may be particularly advantageous in patients undergoing bone marrow transplantation (BMT), who exhibit post-transplant body protein wasting, gut mucosal injury and immunodeficiency. Studies to date indicate that enteral and parenteral glutamine supplementation is well tolerated and potentially efficacious after high-dose chemotherapy or BMT for cancer treatment. Although not all studies demonstrate benefits, sufficient positive data have been published to suggest that this nutrient should be considered as adjunctive metabolic support of some individuals undergoing marrow transplant. However, BMT is a rapidly evolving clinical procedure with regard to the conditioning and supportive protocols utilized. Thus, additional randomized, double-blind, controlled clinical trials are indicated to define the efficacy of glutamine with current BMT regimens.
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PMID:Glutamine supplementation in bone marrow transplantation. 1189 59

Various factors can influence the metabolism of surgical neonates. These include prematurity, operative stress, critical illness, and sepsis. The nutritional management of surgical infants with congenital or acquired intestinal abnormalities has improved after the introduction of parenteral nutrition. This article is focused on the energy and protein metabolism of surgical neonates with particular reference to the metabolic response to operative trauma and sepsis. The metabolic utilization of intravenous nutrients also is discussed. The metabolic response to operative trauma is different between neonates and adults. Infants have high rates of protein turnover and are avid retainers of nitrogen. Energy expenditure increases only transiently (4 to 6 hours) after major surgery in neonates. Protein turnover and catabolism seems not to be affected by major operative procedures in neonates. In neonates on parenteral nutrition, carbohydrate and fat have an equivalent effect on protein metabolism. The main determinants of fat utilization are carbohydrate intake and resting energy expenditure. Parenteral nutrition in surgical neonates is associated with increased production of oxygen-free radicals. This seems to be related to intravenous fat administration. Promoting fat utilization by reducing the carbohydrate to fat ratio in the intravenous diet reduces free radical activity to a similar extent as fat exclusion. Glutamine appears to be safe for use in neonates and infants and is "conditionally essential" in very-low birth weight infants and in septic neonates. Enteral glutamine supplementation in very-low birth weight infants reduces the risk of sepsis. The metabolism of surgical neonates is affected by operative trauma, critical illness, and sepsis. Nutritional support in surgical neonates has a profound impact on outcome. Exogenous glutamine can modulate immune, metabolic, and inflammatory responses. Further investigations are needed to clarify the clinical benefit of parenteral or enteral glutamine administration in surgical neonates.
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PMID:Metabolism and nutritional support in the surgical neonate. 1203 42

Nutrition and immunology are interrelated. Several nutrients like arginine, glutamine, omega-3-fatty acids and nucleotides enhance cellular immunity, modulate tumor cell metabolism and improve clinical outcome in stress situations. Glutamine supplementation has been shown to decrease incidence of sepsis and to reduce length of hospital stay in bone marrow transplant patients, low birth weight infants, surgical and multiple trauma patients. Studies with arginine have shown a reduction in infectious complications and lower mortality, however a better understanding of the biology of arginine is needed. Omega-3-fatty acid supplimentation as in fish oil stimulates the immune system. The beneficial effects of immunonutrition in surgical patients has been demonstrated in several studies. It significantly reduces infectious complications and length of hospital stay. In critically ill patients immunonutrition may decrease infectious complications but it is not associated with a mortality advantage. Pediatric experience is limited, but the future is promising.
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PMID:Immunonutrition. 1206 76

Glutamine and glutamate with proline, histidine, arginine and ornithine, comprise 25% of the dietary amino acid intake and constitute the "glutamate family" of amino acids, which are disposed of through conversion to glutamate. Although glutamine has been classified as a nonessential amino acid, in major trauma, major surgery, sepsis, bone marrow transplantation, intense chemotherapy and radiotherapy, when its consumption exceeds its synthesis, it becomes a conditionally essential amino acid. In mammals the physiological levels of glutamine is 650 micromol/l and it is one of the most important substrate for ammoniagenesis in the gut and in the kidney due to its important role in the regulation of acid-base homeostasis. In cells, glutamine is a key link between carbon metabolism of carbohydrates and proteins and plays an important role in the growth of fibroblasts, lymphocytes and enterocytes. It improves nitrogen balance and preserves the concentration of glutamine in skeletal muscle. Deamidation of glutamine via glutaminase produces glutamate a precursor of gamma-amino butyric acid, a neurotransmission inhibitor. L-Glutamic acid is a ubiquitous amino acid present in many foods either in free form or in peptides and proteins. Animal protein may contain from 11 to 22% and plants protein as much as 40% glutamate by weight. The sodium salt of glutamic acid is added to several foods to enhance flavor. L-Glutamate is the most abundant free amino acid in brain and it is the major excitatory neurotransmitter of the vertebrate central nervous system. Most free L-glutamic acid in brain is derived from local synthesis from L-glutamine and Kreb's cycle intermediates. It clearly plays an important role in neuronal differentiation, migration and survival in the developing brain via facilitated Ca++ transport. Glutamate also plays a critical role in synaptic maintenance and plasticity. It contributes to learning and memory through use-dependent changes in synaptic efficacy and plays a role in the formation and function of the cytoskeleton. Glutamine via glutamate is converted to alpha-ketoglutarate, an integral component of the citric acid cycle. It is a component of the antioxidant glutathione and of the polyglutamated folic acid. The cyclization of glutamate produces proline, an amino acid important for synthesis of collagen and connective tissue. Our aim here is to review on some amino acids with high functional priority such as glutamine and to define their effective activity in human health and pathologies.
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PMID:II. Glutamine and glutamate. 1248 81

Glutamine, a non-essential amino acid, is the most important source of energy for macrophages and lymphocytes. Reduction in its plasma concentration is related with loss of immune function, as leukocyte proliferation and cytokine production. It is well known that glutamine is largely produced by the skeletal muscle which is severely compromised as a consequence of the paralysis due to the damage of the spinal cord. In spinal cord injury (SCI) patients, infections, such as pneumonia and sepsis in general, are a major cause of morbidity and mortality. In comparison with the control group, a 54% decrease in plasma glutamine concentration was observed as well as a decrease in the production of TNF and IL-1 by peripheral blood mononuclear cells cultivated for 48 h in SCI patients. Therefore, we propose that a decrease in plasma glutamine concentration is an important contributor to the immunosuppression seen in SCI patients.
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PMID:Plasma glutamine concentration in spinal cord injured patients. 1602 49

Glutamine (Gln) has been demonstrated to have benefit in the modulation of systemic immunity in sepsis. However, the effects of Gln on local immunity and intra-lymphocyte cytokine expression have not been investigated in mice with gut-derived sepsis. This study evaluated the influence of a Gln-enriched diet on interleukin (IL)-6 expression in organs and Th1/Th2 type cytokine production within lymphocytes in septic mice. Male ICR mice were assigned to control and Gln groups. The control group was fed a semi-purified diet, while in the Gln group, Gln replaced part of the casein. After feeding the respective diets for 3 weeks, sepsis was induced by cecal ligation and puncture (CLP). Mice were sacrificed at 0, 6, 12 and 24h after CLP and their organs were harvested for further analysis. Results showed that IL-6 levels in the liver were decreased, whereas levels were increased in the lungs, kidneys and intestines with the progression of sepsis in both groups. Also, intra-lymphocyte interferon (IFN)-gamma expression decreased and IL-4 expression increased during sepsis. Compared to the control group, the Gln group had higher levels of IL-6 in the liver and lower levels in other organs at various time points. Lymphocyte IFN-gamma expression in the Gln group was higher, and IL-4 levels were lower than those of the control group after CLP. These results suggest that Gln supplementation decreased IL-6 production in non-hepatic organs, while reducing intra-lymphocyte IL-4 and enhancing IFN-gamma expressions. This change may reverse the Th2 type response to a more-balanced Th1/Th2 response during sepsis.
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PMID:Dietary glutamine supplementation modulates Th1/Th2 cytokine and interleukin-6 expressions in septic mice. 1602 97

Glutamine (GLN) has been shown to attenuate cytokine release from LPS-stimulated human peripheral blood mononuclear cells; however, the in vivo antiinflammatory effect of GLN in polymicrobial sepsis and ARDS is unknown. This study evaluates the effect of GLN on inflammatory cytokine release and the pathways that may mediate antiinflammatory effects of GLN in the lung. Either 0.75 g/kg of GLN or saline placebo (SP) was administered to male rats 1 h after cecal ligation and puncture (CLP). NF-kappaB activation, IKBalpha degradation, phosphorylation of p38 MAPK, ERK, and MKP-1 expression were evaluated in lung tissue 6 h post-CLP. Lung tissue iNOS and eNOS, TNF-alpha, IL-6, and IL-18 cytokines were assayed. Last, lung histopathology for occurrence of ARDS and survival were examined. GLN given 1 h postsepsis led to inhibition of lung tissue NF-kappaB activation (P < 0.001 vs. SP), attenuated degradation of IKBalpha, and inhibited phosphorylation of p38 MAPK, and ERK, pathways critical for cytokine release. GLN treatment increased MKP-1 peptide expression and significantly attenuated TNF-alpha and IL-6 6 h after CLP. IL-18 was attenuated by GLN at multiple time points post-CLP. Further, GLN abrogated increases in lung iNOS expression and enhanced lung eNOS postsepsis. Finally, GLN prevented the histopathologic appearance of ARDS after sepsis and significantly improved survival. These data reveal that GLN exerts an antiinflammatory effect in sepsis that may be mediated via attenuation of multiple pathways of inflammation such as NF-kappaB, p38 MAPK, ERK, and MKP-1. GLN also showed an inhibition of increases in iNOS expression. The antiinflammatory effect of GLN was associated with attenuation of ARDS and mortality.
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PMID:GLUTAMINE PREVENTS ACTIVATION OF NF-kappaB AND STRESS KINASE PATHWAYS, ATTENUATES INFLAMMATORY CYTOKINE RELEASE, AND PREVENTS ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS) FOLLOWING SEPSIS. 1631 91


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