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

The role of glucocorticoids in muscle catabolism during sepsis was tested with the glucocorticoid receptor antagonist RU 38486. Sepsis was induced in male Sprague-Dawley rats (40 to 60 gm) by cecal ligation and puncture (CLP). Other animals underwent sham operation. Two hours before CLP or sham operation, rats received RU 38486 (5 mg/kg) or a corresponding volume of vehicle by gavage. Sixteen hours after CLP or sham operation, protein synthesis rate was determined by measuring incorporation of 14C-phenylalanine into protein in incubated extensor digitorum longus muscles. Total and myofibrillar protein breakdown rates were determined by measuring net release of tyrosine and 3-methylhistidine, respectively. The protein synthesis rate was approximately 30% lower in rats with sepsis than in sham operated rats and was not affected by treatment with RU 38486. The total protein breakdown rate was increased by approximately 70% and myofibrillar protein degradation was increased more than fivefold in muscle from rats with sepsis. Treatment with RU 38486 resulted in a 28% reduction of total and a 44% reduction of myofibrillar protein breakdown in rats with sepsis but did not affect proteolysis in muscle from sham-operated animals. The results support a role of glucocorticoids in accelerated muscle proteolysis during sepsis. It is not clear whether glucocorticoids are the only required mediator or they interact with other substances to induce muscle protein breakdown during sepsis.
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PMID:Effect of the glucocorticoid receptor antagonist RU 38486 on muscle protein breakdown in sepsis. 200 52

Pharmacologic therapy designed to block adrenergic activity or alter hormonal milieu may modulate energy and protein metabolism in stress. The metabolic effects of propranolol (beta adrenergic receptor blocker) in sepsis was investigated in 22 well-nourished rats that underwent superior vena caval cannulation, cecal ligation, and puncture. Animals were randomly assigned to receive either a continuous infusion of 0.7 mg/day of propranolol combined with parenteral nutrition (n = 11) or parenteral nutrition alone (n = 11). Both groups received isocaloric, isonitrogenous, isovolemic, parenteral nutrition post-operatively for 24 hr. Nitrogen balance was better for the propranolol group than for the control group (+743 +/- 84 mg/kg/day versus +300 +/- 63 mg/kg/day, respectively, P less than 0.05). A significant difference between the pharmacologic therapy and control groups was noted for urinary 3-methylhistidine excretion versus control (0.99 +/- 0.08 micrograms/kg/day versus 7.5 +/- 0.37 micrograms/kg/day, respectively, P less than 0.01). Measured energy expenditure was similar for both pharmacologic therapy and control groups (149 +/- 20 kcal/kg/day versus 134 +/- 11 kcal/kg/day, respectively, P = N.S.). No statistically significant difference was demonstrated for 24-hr survival between propranolol and control groups (73 and 64%, respectively). Continuous, low-dose propranolol promotes nitrogen retention and decreases 3-methylhistidine excretion without altering energy expenditure in parenterally fed septic rats.
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PMID:Effect of propranolol on nitrogen and energy metabolism in sepsis. 210 45

Administration of extra branched chain amino acids (BCAA) has been associated with a nitrogen sparing effect in septic and traumatized patients. Whether nitrogen sparing is associated with decreased morbidity and mortality rates is unknown. We therefore undertook a prospective, randomized, double blind trial investigating the effects of BCAA enrichment of a total parenteral nutrition (TPN) regimen on nitrogen balance, 3-methylhistidine excretion, morbidity as evidenced by disturbances in organ function, severity of sepsis and mortality. One hundred and one patients entered the study; 52 received a standard TPN solution and 49 a BCAA-enriched solution. Both groups received 30 kcal kg-1 body-weight, 15 per cent fat calories and 0.17 g nitrogen kg-1 body-weight. In the BCAA-enriched group, patients received 0.56 g BCAA kg-1 body-weight (50.2 per cent BCAA). Standard group patients received 0.18 g BCAA kg-1 body-weight (15.6 per cent BCAA). Nitrogen balances and 3-methylhistidine excretion were not significantly different between groups. Although morbidity scores tended to decrease during the study no difference was observed between groups. Mortality (early or late), sepsis or stress-related, did not differ significantly between groups. We were not able to confirm the reported beneficial effects of BCAA-enriched TPN solutions for use in septic and traumatized patients.
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PMID:Effect of branched chain amino acid enrichment of total parenteral nutrition on nitrogen sparing and clinical outcome of sepsis and trauma: a prospective randomized double blind trial. 211 8

The role of prostaglandins in the regulation of muscle protein breakdown is controversial. We examined the influence of arachidonic acid (5 microM), prostaglandin E2 (PGE2) (2.8 microM) and the prostaglandin-synthesis inhibitor indomethacin (3 microM) on total and myofibrillar protein breakdown in rat extensor digitorum longus and soleus muscles incubated under different conditions in vitro. In other experiments, the effects of indomethacin, administered in vivo to septic rats (3 mg/kg, injected subcutaneously twice after induction of sepsis by caecal ligation and puncture) on plasma levels and muscle release of PGE2 and on total and myofibrillar protein breakdown rates were determined. Total and myofibrillar proteolysis was assessed by measuring production by incubated muscles of tyrosine and 3-methylhistidine respectively. Arachidonic acid or PGE2 added during incubation of muscles from normal rats did not affect total or myofibrillar protein degradation under a variety of different conditions in vitro. Indomethacin inhibited muscle PGE2 production by incubated muscles from septic rats, but did not lower proteolytic rates. Administration in vivo of indomethacin did not affect total or myofibrillar muscle protein breakdown, despite effective plasma levels of indomethacin with decreased plasma PGE2 levels and inhibition of muscle PGE2 release. The present results suggest that protein breakdown in skeletal muscle of normal or septic rats is not regulated by PGE2 or other prostaglandins.
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PMID:Prostaglandin E2 does not regulate total or myofibrillar protein breakdown in incubated skeletal muscle from normal or septic rats. 211 60

Elevated temperature has been proposed to contribute to accelerated muscle protein degradation during fever and sepsis. The present study examined the effect of increased temperature in vitro on protein turnover in skeletal muscles from septic and control rats. Sepsis was induced by cecal ligation and puncture (CLP); control rats were sham operated. After 16 h, the extensor digitorum longus (EDL) and soleus (SOL) muscles were incubated at 37 or 40 degrees C. Protein synthesis was determined by measuring incorporation of [14C]phenylalanine into protein. Total and myofibrillar protein breakdown was assessed from release of tyrosine and 3-methylhistidine (3-MH), respectively. Total protein breakdown was increased at 40 degrees C by 15% in EDL and by 29% in SOL from control rats, whereas 3-MH release was not affected. In muscles from septic rats, total and myofibrillar protein breakdown was increased by 22 and 30%, respectively, at 40 degrees C in EDL but was not altered in SOL. Protein synthesis was unaffected by high temperature both in septic and nonseptic muscles. The present results suggest that high temperature is not the primary mechanism of increased muscle protein breakdown in sepsis because the typical response to sepsis, i.e., a predominant increase in myofibrillar protein breakdown, was not induced by elevated temperature in normal muscle. It is possible, however, that increased temperature may potentiate protein breakdown that is already stimulated by sepsis because elevated temperature increased both total and myofibrillar protein breakdown in EDL from septic rats.
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PMID:Effects of elevated temperature on protein breakdown in muscles from septic rats. 218 39

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

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

Pentobarbital therapy has been associated with decreased urinary nitrogen excretion and resting energy expenditure in stressed patients. The metabolic effects of pentobarbital in sepsis were investigated in 29 well-nourished rats who underwent superior vena caval cannulation, cecal ligation, and puncture. Animals were randomly assigned to receive either a continuous infusion of 20 mg/kg/day of pentobarbital combined with parenteral nutrition (n = 13) or parenteral nutrition alone (n = 16). Both groups received isocaloric, isonitrogenous parenteral nutrition postoperatively for 24 hr. Mean nitrogen balance (+/- SEM) was better in the pentobarbital group (+169 +/- 76 mg/kg/day vs -190 +/- 66 mg/kg/day, p less than 0.01). No significant differences between the pentobarbital and control groups were noted for urinary 3-methylhistidine excretion (9 +/- 0.7 micrograms/kg/day vs 11 +/- 0.6 micrograms/kg/day, respectively) or 24 hr survival (77% vs 69%, respectively). Pentobarbital improves nitrogen retention without decreasing urinary 3-methylhistidine excretion in septic rats.
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PMID:Pentobarbital improves nitrogen retention in sepsis. 250 72

The effect of administered human growth hormone (hGH) on protein metabolism in septic rats was investigated. Fifty-three male Wistar rates with SVC cannulation were divided into four groups. Group I (n = 10) underwent sham-operation. Sepsis was induced by cecal ligation in group II (n = 19), group III (n = 10), and group IV (n = 14). Isocaloric, isonitrogenous glucose/amino acids were infused for 4 days. hGH was administered in group III (100 mU/day) and group IV (200 mU/day) every day. Cumulative nitrogen balance (mg/kg) in group IV was significantly higher than in group II (p less than 0.01): group I, 1264 +/- 355; group II, 117 +/- 693; group III, 92 +/- 735; group IV, 1001 +/- 279. Cumulative urinary excretion of 3-methylhistidine (3-MH, mg/kg) did not differ between group II and group IV: group I, 6.2 +/- 0.9; group II, 12.0 +/- 2.2; group III, 13.4 +/- 2.9; group IV, 10.5 +/- 2.3. Serum albumin level in group IV (1.8 +/- 0.2 g/dl) was significantly higher than in group II (1.5 +/- 0.2 g/dl) (p less than 0.01). Blood urea nitrogen level in group IV (12.6 +/- 2.3 mg/dl) was significantly lower than in group II (18.8 +/- 7.4 mg/dl) (p less than 0.05). Although serum levels of glucose, insulin, triglyceride, and phospholipid were higher in sepsis groups than in sham-operated group, those levels did not differ among sepsis groups. Administration of hGH, 200 mU/day, resulted in marked nitrogen retention and had little effect on 3-MH excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of administered human growth hormone on protein metabolism in septic rats. 251 84

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


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