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

Sepsis is a major catabolic insult resulting in a peripheral energy deficit which is made up in part by increased breakdown of lean body mass and oxidation of amino acids, principally the branched chain amino acids. The prognosis in any given case of sepsis is difficult to predict, but should theoretically be related to the degree of disturbance in peripheral energy deficit, which may in turn, be related to plasma amino acid pattern. In order to study whether this hypothesis was correct, plasma amino acids and some of their metabolic byproducts, the beta-hydroxyphenylethanolamines, were studied in 25 septic patients, and were used as discriminant variables in a series of computer performed discriminant analyses and multiple regressions. The two functions tested were the degree of metabolic septic encephalopathy as a determinant of the severity of sepsis and the final outcome in the septic patient. Plasma amino acid patterns exhibited elevated levels of the aromatic and sulfur containing amino acids, phenylalanine, tryosine, tryptophan, methionine, cysteine, and taurine, normal concentrations of alanine, and low normal concentrations of the branched chain amino acids, valine, leucine and isoleucine. Arginine levels, as previously noted, were very low. Patients not surviving the septic episode exhibited higher concentrations of aromatic and sulfur containing amino acids, while patients surviving sepsis had higher concentrations of the branched chain amino acids and arginine. When the degree of encephalopathy as a determinant of the severity of sepsis and step wise discriminant analysis with multiple crescent techniques were used, the best discriminant function between patients with and without encephalopathy was found to result from the interaction of cysteine, methionine, phenylalanine, isoleucine, leucine, and valine. These amino acids gave a correct classification in 82% of patients with no encephalopathy, and 80% of patients with septic encephalopathy. When the same amino acids were used for the discriminant analysis for patients dying of sepsis and patients surviving, the best discriminant function was achieved by using plasma concentrations of alanine, cysteine, methionine, isoleucine, arginine, tyrosine and phenylalanine resulting in 91% of the nonsurvivors, and 79% of the survivors correctly classified. The results suggest a close and significant relationship between the deranged energy metabolism and muscle protein breakdown in sepsis, and the outcome. This further suggests a central role for certain amino acids in perhaps predicting the severity of sepsis and its outcome.
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PMID:Plasma amino acids as predictors of the severity and outcome of sepsis. 38 83

Infections or inflammatory states often cause significant increases in serum phenylalanine and the phenylalanine-tyrosine ratio. More than 95% of samples obtained during inflammatory diseases in man showed phenylalanine-tyrosine ratio increases greater than the maximum normal values. An increase in this ratio also occurred in monkeys with induced Rocky Mountain spotted fever, viral encephalitis, yellow fever, or pneumococcal and Salmonella infections, as well as in rats with pneumococcal and Salmonella infections, as well as in rats with pneumococcal, Salmonella or tularemia infections. A similar ratio increase occurred in rats inoculated with unpurified mediator substances (released by activated leukocytes) that appear to initiate many of the secondary metabolic phenomena associated with infection and/or inflammation. To identify responsible mechanisms, rats were given lethal doses of Streptococcus pneumoniae; serum phenylalanine and phenylalanine-tyrosine ratios increased significantly. Hepatic phenylalanine hydroxylase activities were slightly decreased when compared to noninfected controls. Infected and noninfected rats showed comparable oxidation rates for 14C-phenylalanine given with an oral phenylalanine load, as a pulse-oral dose, or as an intraperitoneal injection. After 8 hr, both infected and control rats had similar amounts of radioactivity in total body protein, but tissue distributions were markedly altered during pneumococcal sepsis. Serum proteins of infected rats contained almost twice as much total radioactivity as that found in controls, while the amount of labeled phenylalanine in skeletal muscle protein was significantly reduced in the infected group. Isolated muscles from infected rats released more phenylalanine and less tyrosine than control muscles. Infection-related increases in serum phenlalanine could not be explained by decreased hydroxylation or oxidation. Rather, the data were consistent with an increased flux of phenylalanine into serum, most likely as the result of increased skeletal muscle catabolism. Elevations in the serum phenylalanine-tyrosine ratio have potential value for estimating the presence of an inflammatory fisease and the catabolic state of a patient.
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PMID:The significance and mechanism of an increased serum phenylalanine-tyrosine ratio during infection. 82 5

The catabolic effects of starvation alone, or starvation in the presence of pneumococcal sepsis, were compared in rats whose skeletal muscle protein had been tagged 14 days earlier with 14C-phenylalanine. In a fed rat, protein catabolism (as estimated by expired 14CO2) is not constant throughout the day but is highest during the dark hours. Starvation is associated with accelerated protein catabolism and a gradual loss of periodicity. Infection increases the rate of catabolism still further and results in a complete loss of periodicity.
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PMID:Total body protein catabolism in starved and infected rats. 90 62

Sepsis is associated with severe muscle wasting. Mechanisms responsible for sepsis-induced alterations in muscle protein metabolism were investigated in vivo and compared with changes induced by nonseptic inflammation. The rate of protein synthesis in mixed hindlimb muscles was not altered in inflammation but was inhibited 50% in sepsis. This inhibition did not result from a decreased RNA content. Instead, the translational efficiency was significantly reduced by 50% in skeletal muscle of septic animals compared with control. The effect of sepsis to lower the rate of protein synthesis was further examined using individual muscles containing different fiber types. Both the protein concentration and protein synthetic rate in fast-twitch muscles were reduced by sepsis, whereas neither of these parameters was affected in slow-twitch muscles or heart. The decreased translational efficiency did not result from a change in the rate of peptide-chain elongation. Instead, the sepsis-induced inhibition of protein synthesis resulted from a restraint in peptide-chain initiation because sepsis caused a 1.6-fold increase in free ribosomal subunits. Overall, sepsis, but not inflammation, caused an inhibition of protein synthesis primarily in muscles composed of fast-twitch fibers. The mechanism involved in the reduced rates of protein synthesis in muscles resulted from an inhibition of peptide-chain initiation, with no change in peptide-chain elongation.
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PMID:Sepsis-induced changes in protein synthesis: differential effects on fast- and slow-twitch muscles. 137 47

In this study we compared the effect of sepsis on muscle protein metabolism in infant (3 to 4 weeks) and adult (3 to 4 months) rats. Sepsis was induced by cecal ligation and puncture (CLP). Control animals underwent sham operation. Sixteen hours after CLP or sham operation, metabolic studies were performed in incubated intact extensor digitorum longus muscles from infant rats or in strips of the same muscle from adult rats. Protein synthesis rate was determined as incorporation of 3H-phenylalanine into protein; total and myofibrillar protein breakdown rates were determined as release of tyrosine and 3-methylhistidine, respectively. Mortality rate following CLP was similar in both age groups. Basal protein synthesis rate was 3 times higher, total protein breakdown rate was 50% higher, and myofibrillar protein breakdown rate was 3 times higher in infant than in adult animals. However, the relative changes in protein turnover rates induced by sepsis were similar in infant and adult rats: protein synthesis rate decreased by approximately 30%, total protein breakdown increased by 40% to 50%, and myofibrillar protein breakdown increased severalfold. The data suggest that despite prominent differences in basal protein turnover rates between infant and adult rats, the effect of sepsis on muscle protein metabolism is not age dependent.
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PMID:Is the metabolic response to sepsis in skeletal muscle different in infants and adults? An experimental study in rats. 147 97

Recent investigations from our and other laboratories indicate that glycogen is a carbon-chain precursor in muscle for the synthesis of TCA cycle intermediates and glutamine. During intense exercise and in conditions of a relative lack of energy (hypoxia, trauma, sepsis) the metabolism of branched-chain amino acids (BCAA) is accelerated in muscle. In the primary BCAA aminotransferase reaction 2-oxoglutarate is used as amino-group acceptor (putting a carbon-drain on the TCA cycle) under formation of glutamate. Glutamate will subsequently react with ammonia, generated in the AMP deaminase reaction or by deamination of amino acids, under formation of glutamine in a reaction catalysed by glutamine synthetase (glutamate + ammonia + ATP--> glutamine + ADP). Muscle glycogen stores may be smaller or less available at high altitude. It is hypothesized that this will lead to premature fatigue (due to both a lack of fuel and of TCA cycle carbon-precursor) and to a reduction in the synthesis rate of glutamine. A chronic reduction in the synthesis rate of glutamine during a long term stay at high altitude on its turn may lead to gut atrophy, bacterial translocation, endotoxemia, muscle protein catabolism and a weakened immune status.
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PMID:Amino acid metabolism, muscular fatigue and muscle wasting. Speculations on adaptations at high altitude. 148 45

The anabolic effect of insulin in skeletal muscle reflects increased protein synthesis and reduced protein degradation. Insulin stimulates protein synthesis mainly at the translational level by enhancing peptide chain initiation. The mechanism by which the hormone reduces protein breakdown is less well understood, but inhibition of the lysosomal pathway is probably an important component. Sepsis results in pronounced muscle catabolism, mainly reflecting increased protein breakdown, particularly myofibrillar protein breakdown, and a less prominent inhibition of protein synthesis. There is evidence that muscle protein breakdown becomes resistant to the effect of insulin during sepsis, probably at the postreceptor level. This insulin resistance may be mediated by increased beta-adrenoreceptor activity. In contrast, the stimulatory effect of insulin on muscle protein synthesis and amino acid transport is maintained during sepsis. The regulatory effect of insulin on muscle protein metabolism may be affected by other catabolic conditions as well, e.g., fasting, denervation, burn injury, and trauma.
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PMID:Regulation by insulin of muscle protein metabolism during sepsis and other catabolic conditions. 148 52

Sepsis is characterized by an increase in the plasma concentration of aromatic amino acids (AAAs) and those containing sulfur and a decrease in the branched-chain amino acids (BCAAs). We studied changes in the plasma aminogram of septic patients given different types of total parenteral nutrition (TPN), analyzing variations in accordance with the type of TPN used and the importance that the use of BCAA may have in these patients. We studied 80 patients with peritonitis divided into two groups of 40 patients each: group 1 was given a solution with 22.5% BCAA and group 2 a solution with 45% BCAA. High BCAA content caused an increase in the plasma concentrations of these amino acids and in the BCAA/AAA quotient and a decrease in AAAs. Plasma concentrations of leucine and valine reached high, potentially toxic levels at 15 days when solutions with high BCAA content were used. Glycine increased in group 1, which may be important because of its tendency to produce hyperammonemia. BCAAs are of unquestioned nutritional importance in view of the evidence of changes that take place in muscle protein catabolism and in plasma amino acids. In the phase of increased protein catabolism, we saw a plasma amino acid pattern in keeping with the existing metabolic situation. The need for BCAA diminishes when the hypercatabolic state disappears.
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PMID:Variations in plasma amino acids in septic patients subjected to parenteral nutrition with a high proportion of branched-chain amino acids. 149 55

The role of tumor necrosis factor (TNF) in the regulation of muscle protein turnover was studied in rats. Protein synthesis and total and myofibrillar protein breakdown rates were measured in incubated extensor digitorum longus muscles. Intraperitoneal administration of recombinant TNF-alpha (300 micrograms/kg of body weight) increased total and myofibrillar protein breakdown rates by 28% and threefold, respectively, with no effect on protein synthesis. In subsequent experiments, sepsis was induced by cecal ligation and puncture or a sham-operation was performed. Rats received TNF antiserum (1 mL/100 g of body weight) or control serum 2 hours before cecal ligation and puncture or sham-operation. Treatment with TNF antiserum reduced the mortality rate from 25% to 5% following cecal ligation and puncture. The treatment had no effect on protein synthesis but reduced total and myofibrillar protein breakdown rates by 26% and 39%, respectively, in septic animals. Results suggest TNF is involved in the regulation of sepsis-induced muscle proteolysis.
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PMID:Evidence that tumor necrosis factor participates in the regulation of muscle proteolysis during sepsis. 154 94

The influence of sepsis on transcription of myofibrillar proteins in skeletal muscle was studied in rats. Sepsis was induced by cecal ligation and puncture (CLP); control rats were sham-operated. Sixteen hours later, muscle levels of mRNA for myofibrillar proteins were determined by using cDNA probes specific for transcripts for alpha actin and myosin heavy chain. Sepsis resulted in a 2-6 fold decrease in alpha actin mRNA levels and an even more pronounced reduction in myosin heavy chain mRNA levels. Results suggest that sepsis-induced reduction of muscle protein synthesis is at least partly regulated at the transcriptional level.
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PMID:Reduced levels of mRNA for myofibrillar proteins in skeletal muscle from septic rats. 187 85


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