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)

Transmucosal passage of bacteria in critically ill patients may lead to a significant incidence of systemic sepsis. This has attracted much clinical interest, as it has been shown that malnutrition in itself, impairs various aspects of barrier function. Bacterial translocation is increased in animal models where nutrients are given by the parenteral route, while enteral feeding reverses this. Translocation is also considerably increased in response to a non-lethal endotoxin challenge, if there is pre-existing protein energy malnutrition. Similar results have been obtained where the insult is caused by the inflammatory agent, zymosan. Dietary fibre reduces the deleterious effects of either agent on translocation, although the type of fibre is important. Bulk forming but non-fermentable fibres are more effective than easily fermentable types (for example, pectin). Glutamine was not effective in preventing elemental diet induced bacterial translocation. Thus, although fermentable fibre and glutamine have positive effects on mucosal mass, they do not affect translocation. Enteral nutrition thus seems to be superior to parenteral nutrition in maintaining the functional barrier of the gut. A clearer understanding of the physiology of these effects may lead to use of specifically modified enteral diets in the critically ill patient.
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PMID:Bacterial translocation: the influence of dietary variables. 812 85

Arginine and ornithine are precursors of nitric oxide and polyamines, respectively. These metabolites intimately participate in permeability and adaptive responses of the gut. The liver possesses high arginase activity as an intrinsic part of urea synthesis and would consume most of the portal supply of dietary arginine. The gut reduces this possibility by converting dietary arginine to citrulline, which effectively bypass the liver and is resynthesized to arginine in the kidney. Dietary ornithine supplementation, in the form of ornithine alpha-ketoglutarate (OKG) can be considered as an arginine precursor. Several supplement studies have shown both amino acids to promote growth hormone and insulin secretion with anabolic effects in postoperative patients. Their intermediary metabolites (for example, glutamine, proline) may also be of benefit in trauma metabolism. Specific effects of either amino acid on the gut are poorly reported. One recent animal study showed improved morphology after OKG administration, perhaps through increased polyamine secretion. Generation of nitric oxide from arginine has two facets. Excess production from high dose arginine potentiated the effects of experimentally induced sepsis, whereas low doses improved survival. These considerations suggest that the role of enteral diet supplementation with arginine or OKG should be urgently examined for any benefits it may have on mucosal barrier function.
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PMID:Can arginine and ornithine support gut functions? 812 89

Glutamine uptake by the liver is accelerated during endotoxemia, but little is known regarding the influence of sepsis on the plasma membrane transport systems catalyzing hepatic glutamine uptake. We hypothesized that this augmented uptake was due to an increase in hepatocyte plasma membrane transport activity. We investigated the activities of the Na(+)-dependent transport System N (transports glutamine into the hepatocyte) and the Na(+)-independent System n (transports glutamine out of the cell) in hepatocyte plasma membrane vesicles (HPMVs) prepared from livers of rats treated with Escherichia coli endotoxin (LPS) in vivo. HPMVs were prepared by differential centrifugation and the transport of [3H]glutamine was assayed by a rapid mixing/filtration technique in the presence and absence of sodium. Vesicle integrity and functionality were confirmed by enzyme marker enrichments and classic "overshoots" in the presence of sodium. Carrier-mediated Na(+)-independent glutamine transport activity was not altered by LPS administration. In contrast, endotoxemia resulted in a time- and dose-dependent two- to threefold increase in Na(+)-dependent glutamine transport activity in HPMVs secondary to an increase in the transport Vmax, consistent with the appearance of increased numbers of corresponding transporter proteins in the hepatocyte plasma membrane. The Km (affinity for glutamine) of the System N transporter was not affected by LPS treatment. Maximal increases in transport were observed 4 hr after exposure to endotoxin. System N transport activity returned to basal levels by 12 hr. This increase in transport activity represents an important mechanism regulating the accelerated hepatic glutamine uptake that occurs during severe infection.
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PMID:Endotoxin increases hepatic glutamine transport activity. 836 Nov 64

The concentrations of glutamine and other amino acids were measured in plasma and intracellular fluid of soleus and extensor digitorum longus (EDL) muscles of rats 4, 8, and 16 hr after induction of sepsis by cecal ligation and puncture or after sham operation. Previous studies have shown that muscle protein breakdown is greatly increased in EDL, but not in soleus muscle, in this sepsis model. Corresponding to previous observations of protein breakdown in sepsis, muscle glutamine was markedly depleted (< 50%) in EDL by sepsis, while no significant fall in glutamine concentration in soleus was observed. Changes in muscle glutamine concentration in sepsis could not be attributed to changes in the precursor of glutamine, glutamic acid. Data were examined for changes consistent with hypothesized alterations in glutamine transport. Correlations among glutamine and other amino acids in muscle, histidine in particular, were consistent with a sepsis-induced alteration in activity of the sarcolemmal glutamine transporter, system Nm. These results thus strengthen the proposed connection between muscle glutamine content and muscle protein metabolism under catabolic conditions.
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PMID:Intracellular glutamine concentration does not decrease in all muscles during sepsis. 841 65

This study of the plasma aminogram was done on 35 patients with a moderate to high level of stress and/or sepsis. For the criteria of illness, the SAPS (Simplified Acute Physiological Score) was used on their admission to the intensive Care Unit, and the diagnosis of sepsis was established according to the criteria of Jacobs and Boone. The stress level was calculated according to Bistrian. The plasma aminogram was determined with High Resolution Liquid Chromatography. The plasma samples were taken while nutrient units containing what is considered a standard solution of amino acids were infused. The eight essential amino acids (EAA) and 10 non-essential were quantified. The ratio of ramified to aromatic amino acids (RAA/AAA) was calculated by Fisher's criteria. An increase in AAA (phenylalanine, p < 0.001, and tyrosine, NS) and sulphur containing amino acids (methionine, p < 0.001) was found. The RAA were within normal ranges (valine) or increased (leucine, p < 0.001 and isoleucine, p < 0.001). The RAA/AAA ratio was reduced, p < 0.0001. Glycine was increased, p < 0.0001 and alanine reduced, p < 0.05. Glutamine and glutamic acid were reduced, p < 0.0001 and p < 0.01 as was arginine, p < 0.001. No difference was found in the total concentration of AA. The results confirm the standard plasma aminogram described in situations of metabolic stress and/or sepsis.
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PMID:[Plasma aminogram in critical patients]. 846 96

Ischaemic ileocolitis in postoperative course of major abdominal surgery is a great challenge for the surgeon: the mortality rate is very high, and therapeutic choices are poor. In the elderly patients ischaemic bleeding ileocolitis is often determined by low flow: sepsis and cytologic damage are primed by activation of endotoxins and chemical mediators, and bacterial translocation could develop across intestinal wall. In our case the patient (male, caucasian, 68 years old) underwent bilio-hepatic resection for hilar cholangiocarcinoma. In the postoperative period continuous enteric haemorrhage was determined by an ischaemic ileocolitis demonstrated by colonoscopy. Abdominal angiography did not show stenosis or occlusion of mesenteric vessels. We administered dopamine and dobutamine as vasodilator drugs for splanchnic circulation without any positive response. Surgical removal of the colon was unsuccessful to stop bleeding. ileostomy and sigmostomy were performed. Histologic samples of the specimen showed ischaemic ileocolitis. After a few days the patient bled again. As last therapeutic choice, we bubbled oxygen in a solution of L-glutamin 500 mml (3 liters/min for 5 min). We administered 500 mml of this solution three times a day by enteral sond, and 100 mml twice a day by sigmoidostomy and endoluminal oxygenation was performed twice a day (1l/min for 1-2 minutes) under continuous control. Bleeding was reducing during the next five days, until stopping. If glutamine and O2 can be considered the fuel of enterocytes, we hypothesized endoluminal oxygenation and glutamine enteral supply of the small intestine could feeding enterocytes, until a complete restoration of enteral mucosa and stopping of the haemorrhage.
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PMID:[Postoperative ischemic ileocolitis in the elderly. Suggested therapy with intraluminal administration of oxygen and glutamine]. 852 47

Classical galactosaemia, deficiency of galactose-1-phosphate uridyltransferase (GALT), is characterized by acute symptoms of hepatomegaly, jaundice, sepsis, cataracts and growth retardation. Treatment with dietary galactose restriction corrects these complications immediately; however, most of these children develop long-term complications of verbal dyspraxia, mental retardation and ovarian failure. Our previous molecular study showed that the most common mutation of the GALT gene is a missense mutation of Q188R (replacement of glutamine-188 by arginine) in approximately 60-65% of the German galactosaemic population. The coding region of GALT was amplified by the polymerase chain reaction from genomic DNA of classical galactosaemic individuals, who are negative or heterozygous for Q188R, and was further characterized by direct sequencing. Three new disease-causing mutations, two missense and a stop codon mutation, were identified in three patients from two families with mild galactosaemic variants: firstly R67C, replacement of arginine-67 by cysteine and W316X, the stop codon at tryptophan-316 in one male; secondly A330V, replacement of alanine-330 by valine in two female siblings. In the first family the patient was also heterozygous for the polymorphism N314D and in the second family both girls were compound heterozygotes for Q188R and A330V. All three galactosaemic individuals have a considerable amount of the residual GALT activity in RBC and the galactose-1-phosphate (GALP) level decreased much faster on treatment than that of other galactosaemic patients with missense mutations such as Q188R. The clinical and biochemical data of these patients were much more favourable in comparison with those of two female galactosaemic individuals, one homozygous for L195P and the other compound heterozygous for Q188R and L195P. These three missense mutations (R67C, L195P and A330V) also occur in highly conserved regions. These observations suggest that the phenotypic variation in galactosaemic individuals may be due to different molecular aetiologies.
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PMID:Mutations in the galactose-1-phosphate uridyltransferase gene of two families with mild galactosaemia variants. 859 37

Glutamine is important for the function of lymphocytes and macrophages. A role for the high rate of glutamine utilisation by these cells is presented. Since muscle syntheses, stores and releases glutamine, this tissue may play a role in the immune response. Since the number of immune cells utilising glutamine may be large, the demand for glutamine from muscle, especially during trauma, sepsis or burns, may be very high. A speculative suggestion is put forward that this requirement for glutamine from muscle may play a role in cachexia under some of these conditions.
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PMID:The possible role of glutamine in some cells of the immune system and the possible consequence for the whole animal. 864 82

Glutamine is a non essential amino acid. Nevertheless it has to be considered a "conditionally essential" amino acid for several metabolic reactions in which it is involved. Glutamine is the most abundant amino acid in human plasma and muscle. Because glutamine is highly unsteady, it was never used for enteral and parenteral nutrition in the past. It appears to be a unique amino acid for rapidly proliferating cells serving as a preferred fuel compared to glucose. It seems to be essential for cellular replication such as a "nitrogen carrier" between the tissues. A deficiency state of glutamine causes morphology and functional changing and negative nitrogen metabolism. The need for glutamine is particularly high when metabolism is increased as in the critically ill (surgical stress, sepsis, inflammatory states, fasten, burns) especially in the tissues with a rapid cell turn-over. In these conditions the body requirements of glutamine appear to exceed the individual's muscle deposits (muscle is the most important place of synthesis and storage), causing an increased synthesis with a high energy waste and loss of muscle mass. Glutamine is essential for bowel mucosa trophism and its deficiency in all the catabolic states allows bacterial translocation. In these cases feeding is not sufficient to restore basal conditions. At present enteral or parenteral glutamine supplementations are of high interest for the feeding of critically ill patients.
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PMID:[The metabolic role of glutamine]. 865 37

"Septic autocannabalism" been coined to describe the metabolic response that follows severe sepsis in humans. The normal protein- and energy-conserving mechanisms evoked during simple starvation are not observed following the onset of sepsis. The metabolic response to sepsis entails rapid breakdown of the body's reserves of protein, carbohydrate, and fat. Hyperglycemia with insulin resistance, profound negative nitrogen balance, and diversion of protein from skeletal muscle to splanchnic tissues are prominent features. These responses are believed to be mediated in large part by inflammatory cytokines such as tumor necrosis factor alpha (TNFalpha), interleukin 1beta (IL-1beta), and IL-6. Secondary induction of catecholamines, cortisol, and glucagon by cytokines is likely to be another important effector mechanism. Infection and inflammation elicit a complex network of interwoven responses, and no single mediator alone accounts for the responses observed. Sepsis also commonly involves alterations in cardiovascular function with altered flow to key metabolic sites, hypoxia, damage to the gut's mucosal barrier, secondary organ failure, and alterations in capillary permeability. These structural and functional alterations also strongly influence the metabolic profile during infection. If these catabolic responses persist for more than a few days, severe malnutrition results and is likely to be an important risk factor for mortality in these patients. The altered metabolic milieu during sepsis prevents effective use of exogeneously delivered glucose and protein; at best, administration of these agents ameliorates but does not prevent the persistence of catabolism. Delivery of agents that antagonize cytokines and other moieties such as glutamine and growth hormone may, in the future, help to restore nitrogen balance during sepsis.
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PMID:Metabolism of sepsis and multiple organ failure. 866 35


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