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)

Sepsis, like trauma, causes proteolysis of skeletal muscle. Insulin normally protects against muscle protein degradation. In earlier work using a rat muscle preparation, insulin inhibition of proteolysis decreased in the presence of plasma from injured patients. The current experiments tested the effect of plasma from septic patients on insulin inhibition in the same model. The mean value of protein degradation among eight septic plasma samples was 49% greater than the mean value among five normal plasma samples in soleus muscle and 45% greater in extensor digitorum longus muscle. In the presence of insulin, 10(3) mU/L, the increases in degradation with septic plasma were 42% in soleus muscle and 48% in extensor digitorum longus muscle. Insulin reduced degradation an average of 6% (soleus) and 10% (extensor digitorum longus) in normal plasma and 10% (soleus) and 8% (extensor digitorum longus) in septic plasma. In contrast to results of other studies, these experiments show that the protective effect of a moderate concentration of insulin in resisting muscle protein degradation is not significantly different in the muscle protein degradation is not significantly different in the presence of septic human plasma compared with normal plasma. This finding supports clinical efforts to decrease proteolysis in septic patients by the administration of insulin.
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PMID:Insulin protects against muscle proteolysis induced by septic plasma. 240 29

The major determinants of urea production were investigated in 26 patients with multiple trauma (300 studies). The body clearances (CLRs) of ten amino acids (AAs) were estimated as a ratio of muscle-released AAs plus total parenteral nutrition-infused AAs to their extracellular pool. While clinically septic trauma (ST) patients without multiple-organ failure syndrome (MOFS) had a higher level of urea nitrogen production (25.6 +/- 13.4 g of N per day) compared with nonseptic trauma (NST) patients (14 +/- 7.5 g of N per day) and with ST patients with MOFS (4.28 +/- 1.5 g of N per day), in all groups urea N production was found to be a function of muscle protein degradation (catabolism), total parenteral nutrition-administered AAs, and the ratio between leucine CLR and tyrosine CLR (L/T) (r2 = .82, P less than .0001). Since tyrosine is cleared almost exclusively by the liver, the L/T ratio may be regarded as an index of hepatic function. The significant differences between urea N production in ST and NST patients lay in an increased positive dependence on muscle catabolism and increased negative correlation with L/T in the ST group. At any L/T ratio, urea N production was increased in ST patients over NST patients, but in ST patients with MOFS, it fell to or below levels of NST patients. These data show that the ST process is associated with enhancement of ureagenesis, due to increased hepatic CLR of both exogenous and endogenous AAs. In sepsis with MOFS, a marked inhibition of urea synthesis occurs, partially explained by a decreased hepatic CLR of non-branched-chain AAs.
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PMID:Determinants of urea nitrogen production in sepsis. Muscle catabolism, total parenteral nutrition, and hepatic clearance of amino acids. 249 41

Numerous investigations have been performed on catabolism in polytrauma and surgery. Comparable studies on the internal medical intensive-care patient are not available. Such patients have an increasing metabolism with a maximum attained on day 5, and the catabolic condition is associated with an increased muscle protein breakdown. Objective measurements of catabolism and nutritional status are important but difficult. The recovery of a patient after acute illness depends on the provision of sufficient and adequate nutrition in three steps: 1. quantity and quality of calories; 2. quantity and quality of protein; 3. vitamins and electrolytes. Glucose is one source of calories as are fructose, xylit, and fat. Quantity and quality of amino acids are relative to organ failure and disturbance of amino acid metabolism. Branched-chain amino acids may be helpful in hepatic failure and severe sepsis.
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PMID:[Catabolism and artificial nutrition of the internal medicine intensive care patient]. 251 76

There are widespread disturbances in hepatic and peripheral metabolism in sepsis. Prominent effects include elevated plasma concentrations of aromatic and sulfur-containing amino acids during sepsis, while BCAA are normal or reduced. These alterations probably in part reflect accelerated muscle protein breakdown and hepatic dysfunction. Concomitant with changes in plasma amino acids, altered brain levels of amino acids and neurotransmitters are observed. Increased brain concentrations of the serotoninergic and reduced levels of the catecholaminergic neurotransmitters, along with the occurrence of false neurotransmitters, may be important factors in the pathophysiology of septic encephalopathy. Although the main objective in the treatment of septic patients, of course, is to remove or drain the septic focus, recent studies have shown that administration of BCAA-enriched solutions may be beneficial in the improvement of metabolic derangements and septic encephalopathy. It should be emphasized that not a great deal of work has been done in this area, and the above results are preliminary and fragmentary. However, they do at least provide a working hypothesis for testing of another form of metabolic encephalopathy.
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PMID:Septic encephalopathy. Etiology and management. 287 41

A carrier for glutamine, identified in rat muscle, has properties in terms of kinetics, ion dependence and hormone sensitivity, and effects of endotoxin and branched-chain aminoacids that point to an important function in the control of whole-body aminoacid metabolism. The existence of a link between the size of the glutamine pool in muscle and the rate of muscle protein synthesis raises possibilities for therapeutic interventions to limit protein loss in injury, sepsis, and chronic disease.
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PMID:Characteristics of a glutamine carrier in skeletal muscle have important consequences for nitrogen loss in injury, infection, and chronic disease. 287 74

Anastomotic leakage and fistula of alimentary tract are accompanied by peritonitis because of exudation of contents in the digestive canal. In order to inquire about metabolism of protein and amino acids in surgical infection, this study was performed by the method of a time related cross-over trial, comparing high branched chain amino acids (BCAA) solution with low BCAA solution. The following results were obtained. When metabolism is physiologically compensated in infection, it was suggested that there appeared to be gluconeogenesis, ureagenesis and a liver disturbance accompanied in the early phase of sepsis. Administration of BCAA leads to an inhibition of muscle protein break down and a promotion of visceral protein synthesis in the case of severe infection. Administration of BCAA enriched amino acids solution have an important therapeutic measure under severe stressed condition and a significant role in medicine.
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PMID:[Clinical study of protein and amino acids metabolism in surgical infection--significance of administration of branched chain amino acids]. 309 63

More than one thousand publications have demonstrated the safety and efficacy of today's lipid emulsions including long chain fatty acids under experimental and clinical conditions. This has resulted in a general acceptance of a dual energy system comprising both carbohydrates and lipids as non-protein calories in total parenteral nutrition. Non-carnitine-dependent fatty acid has been suggested as a superior energy source in clinical situations where carnitine may be in the subnormal range. A medium chain triglyceride (MCT) emulsion would provide an energy source with a more readily oxidizable substrate. The tolerance of MCT is less than that of long chain triglyceride (LCT), whereby only physical mixtures of these emulsions will be used in humans. A structured lipid (SL) is a triglyceride which includes both medium and long chained fatty acids within the same triglyceride. Emulsions including SL have demonstrated a decreased protein energy expenditure and increased serum albumin in burned animal. The SL has also been superior to LCT emulsions in stimulating muscle protein synthesis and maintaining body weight in hepatectomized animals. These positive effects on protein kinetics have been concomitant with a lower RES involvement during septicemia in burned guinea pigs. Emulsions including fatty acids with odd-number carbons give a possibility to provide a fat emulsion which also could contribute positively to the glucose homeostasis. The omega-3 family of fatty acids has demonstrated a potential pharmacologic effect with regard to their ability to decrease blood viscosity and improve survival rate in endotoxin shock in an experimental model. These observations have been ascribed to changes in thromboxin A2 levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New developments in lipid emulsions for parenteral nutrition. 311 89

During sepsis or after injection of endotoxin into rats, there is a large increase in muscle protein breakdown and prostaglandin E2 (PEG2) production. Prior studies showed that partially purified interleukin 1 (IL-1) from human monocytes can stimulate these processes when added to isolated rat muscles. The availability of pure recombinant IL-1 and other monokines has allowed us to investigate the identity of the active agent in this process. Incubation of muscles with recombinant human or murine IL-1 alpha or IL-1 beta or with IL-1 plus a phorbol ester did not stimulate muscle proteolysis or PGE2 production. Homogeneous natural porcine IL-1 ("catabolin") and mouse or human IL-1 beta were also not effective in vitro. In addition, a variety of other human cytokines, including tumor necrosis factor ("cachectin"), epidermal thymocyte-activating factor, eosinophil cytotoxicity-enhancing factor, interferon-alpha, beta, and gamma, platelet-derived growth factor, and transforming growth factor (TGF) beta, which are all released by activated macrophages, TGF-alpha, or mixtures of these polypeptides, also failed to activate proteolysis or PGE2 production. By contrast, a large increase in net protein breakdown could be induced in the rat soleus by polypeptides released from porcine monocytes or by the serum from febrile cattle which had been injected with Pasteurella haemolytica or bovine rhinotracheitis virus. Therefore, a still-unidentified product of activated monocytes appears to be responsible for the negative nitrogen balance that accompanies infectious illness.
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PMID:Activation of protein breakdown and prostaglandin E2 production in rat skeletal muscle in fever is signaled by a macrophage product distinct from interleukin 1 or other known monokines. 328 11

The mechanisms of accelerated skeletal muscle protein degradation during sepsis have not been fully elucidated. Activity of the lysosomal protease cathepsin B is increased in skeletal muscle during various catabolic states other than sepsis. In the present study the protein degradation rate and cathepsin B activity were determined in extensor digitorum longus and soleus muscles from nonseptic and septic rats. The protein degradation rate during incubation in vitro with or without the cathepsin B inhibitor leupeptin was also determined. Both protein degradation and cathepsin B activity were increased in muscles from septic rats. Incubation with leupeptin reduced, but did not normalize, the protein degradation rate in both extensor digitorum longus and soleus muscles from septic animals. These studies suggest that increased cathepsin B activity contributes to the accelerated muscle proteolysis seen during sepsis and that proteases other than cathepsin B are also involved.
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PMID:Evidence that cathepsin B contributes to skeletal muscle protein breakdown during sepsis. 334 5

It has been suggested that leucine and alpha-ketoisocaproic acid (KIA) stimulate protein synthesis and reduce protein breakdown and may be useful in the treatment of muscle catabolism during sepsis. However, whether leucine and KIA regulate protein turnover in septic skeletal muscle is not known. In this study, intact muscles from untreated normal rats or from rats subjected to cecal ligation and puncture were incubated in the presence of leucine or KIA. In normal muscle, leucine stimulated protein synthesis and reduced protein degradation, while KIA decreased protein breakdown. In septic muscle, protein synthesis was also stimulated by leucine, but only at a concentration higher than that needed to affect protein synthesis in normal muscle. Protein breakdown in septic muscle was unaffected by leucine and KIA even at an extracellular concentration as high as 5 mmol/L. Since other experiments showed that the intracellular concentration of leucine was not different in incubated normal and septic muscles, these results suggest that sepsis induces changes in skeletal muscle protein turnover that are resistant to the effects of leucine.
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PMID:Protein synthesis and degradation in skeletal muscle from septic rats. Response to leucine and alpha-ketoisocaproic acid. 335 90


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