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

Increased plasma levels of the catabolic hormones glucagon, epinephrine, and cortisol have been implicated in mediating various metabolic alterations in trauma and sepsis. Their role in altered protein turnover and amino acid transport in skeletal muscle during sepsis, however, is not known. In the current study, rats were infused with a mixture of the catabolic hormones for 16 hours. Control animals were infused with vehicle solution. Protein synthesis and degradation rates were measured in incubated, intact soleus muscles as incorporation of 14C-phenylalanine into protein and release of tyrosine into incubation medium, respectively. Muscle amino acid uptake was determined by measuring the intracellular to extracellular ratio of [3H]-alpha-aminoisobutyric acid after incubation for 2 hours. Infusion of catabolic hormones for 16 hours resulted in elevated plasma glucose and lactate levels, reduced plasma concentrations of most amino acids, and accelerated muscle protein breakdown, similar to previous findings in septic rats. Protein synthesis rates and amino acid uptake in incubated muscles were not significantly different in control and hormone-infused rats. The current study suggests that increased muscle proteolysis in sepsis and severe injury may be mediated in part by catabolic hormones. In contrast, reduced muscle protein synthesis and amino acid uptake are probably signaled by other substances or mechanisms.
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PMID:Effect of catabolic hormone infusion on protein turnover and amino acid uptake in skeletal muscle. 230 36

Muscles from fed or 72-hour fasted rats were incubated in the presence of plasma from septic rats, recombinant interleukin 1 alpha (rIL-1 alpha), or recombinant tumor necrosis factor alpha (rTNF alpha), and breakdown of total and myofibrillar protein was assessed by determining release of tyrosine and 3-methylhistidine, respectively. Septic plasma stimulated total protein breakdown in muscles from 72-hour fasted rats by 10% to 20%, while myofibrillar protein breakdown was not affected. When septic plasma was added to muscles from fed rats, neither tyrosine nor 3-methylhistidine release was altered. Various concentrations of recombinant interleukin 1 alpha or recombinant tumor necrosis factor alpha did not affect total or myofibrillar protein breakdown. Since septic plasma did not stimulate myofibrillar protein breakdown, the role of a circulating factor for muscle proteolysis during sepsis remains unclear.
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PMID:Is there a circulating proteolysis-inducing factor during sepsis? 232 18

Cachexia in tumour-bearing patients involves loss of skeletal muscle proteins. In order to elucidate the mechanisms underlying this phenomenon, we tested the hypothesis of the presence of a circulating proteolytic factor (possibly interleukin-1, acting through an increased PGE2 release) in the plasma of cancer patients, because such a mechanism has been demonstrated in patients with sepsis or trauma and in animals with bacteraemia or viraemia. The effect of plasma from 13 malnourished cancer patients and 14 controls on PGE2 release and protein degradation (assessed as Tyr release) in rat diaphragm in vitro was evaluated; human recombinant interleukin-1 alpha (IL-1) was used for comparison. IL-1 increased PGE2 release (+44% at 5 U/ml), but did not greatly affect proteolysis. On the contrary, human plasma (125 microliters/ml) from both control and tumour-bearing individuals did not affect PGE2 release significantly, but greatly reduced Tyr release. The decrease in Tyr release by plasma was dose-dependent. In conclusion, our data indicate that, at variance with what was demonstrated in patients with trauma or sepsis, loss of skeletal muscle proteins in cancer patients is not mediated by a circulating factor. In addition, evidence is provided of dissociation between PGE2 and Tyr release and of lack of proteolytic activity for IL-1.
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PMID:Effect of plasma from cancer patients on rat skeletal muscle protein degradation and PGE2 release in vitro. 233 Mar 45

The mediators and mechanisms of muscle proteolysis in sepsis are not fully known. We investigated the role of corticosterone in increased muscle proteolysis during sepsis in rats. In one series of experiments, plasma corticosterone and total and myofibrillar protein breakdown rates, determined in incubated extensor digitorum longus muscles as release of tyrosine and 3-methylhistidine, respectively, were measured 16 hr after sham operation (control) or cecal ligation and puncture (sepsis). In other experiments, corticosterone (10 mg/100 g body wt) was injected subcutaneously twice over 16 hr; thereafter, plasma hormone levels and muscle protein breakdown rates were determined. Plasma corticosterone was increased from 14 +/- 1 micrograms/dl in control rats to 38 +/- 8 micrograms/dl in septic rats and total and myofibrillar protein breakdown rates were increased by 99 and 326%, respectively, in muscles from septic rats. When administration of corticosterone resulted in plasma levels similar to those observed in septic rats, total or myofibrillar protein breakdown rates were not altered. The results suggest that corticosterone alone is not responsible for increased muscle proteolysis in septic rats. The data, however, do not rule out the possibility that glucocorticoids may be a cofactor to some other substance or substances in the induction of muscle proteolysis during sepsis.
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PMID:Corticosterone alone does not explain increased muscle proteolysis in septic rats. 233 24

Regional amino acids and brain neurotransmitters were studied in 33 normal and 32 rats with sepsis (induced by cecal ligation and puncture) infused with different amino acid formulations. The brain amino acid pattern during sepsis showed increased concentrations of most essential and six of the nonessential amino acids. The most consistent finding was the accumulation of indoleamines in all six brain regions studied during sepsis; increased brain tryptophan levels presumably resulted in enhanced metabolism of serotonin (5HT), increased production of 5-hydroxyindoleacetic acid (5HIAA), and a high 5HT/5HIAA ratio. Infusion of branched-chain amino acid-enriched formulas restored brain amino acid and neurotransmitter profiles, decreasing levels of tryptophan, tyrosine, 5HIAA, and 5HT/5HIAA ratios while increasing norepinephrine levels in some regions. These alterations in brain neurotransmitter metabolism may be at least partially responsible for the development of septic encephalopathy.
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PMID:Regional brain amino acid and neurotransmitter derangements during abdominal sepsis and septic encephalopathy in the rat. The effect of amino acid infusions. 241 5

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

The effects of two parenteral nutrition (PN) amino acid solutions (FreAmine II and F080) on the serum amino acid levels of 51 children, 27 affected by multiple trauma and 24 by bacterial sepsis, and aged from 1 month to 12 years, were studied. Serum amino acids were determined on day 1 immediately before administrating PN, and on day 5 during PN. Trauma patients on F080 exhibited higher levels of alanine, aspartate, asparagine, leucine, isoleucine, valine, total branched-chain amino acids (BCAA) and total essential amino acids than those on FreAmine II; in contrast septic children showed similar levels of serum amino acids on both PN solutions. BCAA were lower in septics than in trauma patients, probably as a consequence of an increased utilization of these amino acids in sepsis because of the higher organ protein synthesis typical of this situation. The phenylalanine/tyrosine ratio was found elevated both in septic and trauma children, but it decreased after PN in the latter when using an enriched BCAA solution. Utilization of this solution, partly corrects the metabolic disturbances induced by stress, but the metabolical responses induced either by sepsis or trauma are partially different which may have important implications for patient care.
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PMID:Differences in the serum amino acid pattern of injured and infected children promoted by two parenteral nutrition solutions. 249 66

Proteolysis is increased in sepsis, but it is not known whether myofibrillar and non-myofibrillar proteins are broken down in the same fashion, or respond to the same regulatory forces as in non-septic muscle. In this study, therefore, the effect of sepsis on total and myofibrillar protein breakdown in incubated rat extensor digitorum longus (EDL) and soleus (SOL) muscles was determined, and the response in vitro to different concentrations of insulin (10 to 10(5) microU/mL) of protein degradation was studied in incubated EDL muscles from control and septic rats. Sepsis was induced in rats weighing 40 to 60 g by cecal ligation and puncture (CLP). Control animals were sham operated. Sixteen hours after CLP or sham operation, intact EDL and SOL muscles were incubated for two hours in oxygenated Krebs-Henseleit bicarbonate buffer containing glucose (10 mmol/L) and cycloheximide (0.5 mmol/L), and total and myofibrillar protein breakdown was assessed from release into incubation medium of tyrosine and 3-methylhistidine (3-MH), respectively. Tyrosine and 3-MH were determined fluorometrically by high performance liquid chromatography (HPLC). Tissue levels of tyrosine and 3-MH remained stable both in control and septic muscles during incubation for two hours. The rate of tyrosine release was increased during sepsis by 58% (P less than .001) and 15% (NS) in EDL and SOL muscle, respectively. The corresponding figures for 3-MH were 103% (P less than .001) and 21% (NS). Tyrosine release was reduced by insulin at a concentration of 10(3) microU/mL in control muscle and at a concentration of 10(4) microU/mL in septic muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Total and myofibrillar protein breakdown in different types of rat skeletal muscle: effects of sepsis and regulation by insulin. 266 65

Circulating factors produced by the macrophages mediate skeletal muscle proteolysis in sepsis and trauma. This study was done to determine whether cytokines affect skeletal muscle metabolism in cancer. Using a method initially developed to measure proteolytic factors in sepsis and trauma, plasma from cachectic cancer patients, noncachectic cancer patients, and normal controls was tested for effects on normal rat skeletal muscle (soleus, extensor digitorum longus). The experimental design allows concomitant measurement of protein synthesis, by [14C]phenylalanine uptake, and protein degradation, by tyrosine release. Plasma from cancer patients caused no acceleration of protein degradation. Noncachectic cancer plasma acted synergistically with insulin to increase protein synthesis (P less than 0.05). These results indicate that a growth factor is present in the plasma of cancer patients who have not become cachexic. To our knowledge, this is the first documentation of a cancer plasma growth factor acting at the organ level to induce synthesis. Our data refute the theory that cancer cachexia is mediated by circulating proteolytic factors. In a separate experiment, purified human recombinant tumor necrosis factor (rTNF) was incubated with normal rat skeletal muscle. No changes were seen in synthesis or degradation rates. Skeletal muscle proteolysis does not appear to be directly induced by rTNF.
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PMID:Effect of cancer plasma on skeletal muscle metabolism. 268 6

Because high calcium concentration in vitro stimulates muscle proteolysis, calcium has been implicated in the pathogenesis of increased muscle breakdown in different catabolic conditions. Protein breakdown in skeletal muscle is increased during sepsis, but the effect of sepsis on muscle calcium uptake and content is not known. In this study the influence of sepsis, induced in rats by cecal ligation and puncture, on muscle calcium uptake and content was studied. Sixteen hours after cecal ligation and puncture or sham operation, calcium content of the extensor digitorum longus (EDL) and soleus (SOL) muscles was determined with an atomic absorption spectrometer. Calcium uptake was measured in intact SOL muscles incubated in the presence of calcium 45 (45Ca) for between 1 and 120 minutes. Total and myofibrillar protein breakdown was determined in SOL muscles, incubated in the presence of different calcium concentrations (0; 2.5; 5.0 mmol/L), and measured as release into the incubation medium of tyrosine and 3-methylhistidine (3-MH), respectively. Calcium content was increased by 51% (p less than 0.001) during sepsis in SOL and by 10% (p less than 0.05) in EDL muscle. There was no difference in 45Ca uptake between control and septic muscles during the early phase (1 to 5 minutes) of incubation. During more extended incubation (30 to 120 minutes), muscles from septic rats took up significantly more 45Ca than control muscles (p less than 0.05). Tyrosine release by incubated SOL muscles from control and septic rats was increased when calcium was added to the incubation medium, and at a calcium concentration of 2.5 mmol/L, the increase in tyrosine release was greater in septic than in control muscle. Addition of calcium to the incubation medium did not affect 3-MH release in control or septic muscle. The results suggest that calcium uptake and content in skeletal muscle are increased during sepsis and that high calcium concentrations in vitro stimulate nonmyofibrillar protein breakdown. Muscles from septic animals may be more sensitive to the effect of calcium in vitro than muscles from nonseptic rats. Whether increased calcium uptake and content in skeletal muscle is partly responsible for accelerated muscle proteolysis during sepsis remains to be determined.
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PMID:Effect of sepsis on calcium uptake and content in skeletal muscle and regulation in vitro by calcium of total and myofibrillar protein breakdown in control and septic muscle: results from a preliminary study. 274 Sep 90


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