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 was induced by cecal ligation and puncture in male Sprague-Dawley rats weighing approximately 70 g and the animals were intravenously infused with one of four isocaloric solutions: group I (N = 16), 8.5% dextrose solution; group II (N = 16), alpha-ketoisocaproic acid (KIA, 5.1 mg/ml) in 8.5% dextrose; group III (N = 16), FreAmine HBC (containing 45% branched-chain amino acids) in 2.5% dextrose; and group IV (N = 17), FreAmine HBC in 2.5% dextrose + KIA (5.1 mg/ml). Eighteen hr after induction of sepsis, extensor digitorum longus (EDL) and soleus (SOL) muscles were dissected with intact tendons and incubated for the study of protein synthesis and degradation, which were measured as incorporation of 14C-phenylalanine into protein and release of tyrosine into incubation medium, respectively. Urine was collected for determination of nitrogen balance. Nitrogen balance, which was equally negative in groups I and II, was significantly improved in groups III and IV and became equally positive in these groups. Protein synthesis and degradation rates in incubated EDL and SOL muscles were similar to those which we have reported previously in septic rats. Except for a higher synthetic rate in SOL in group II, no other differences in protein synthesis or degradation rates between the four experimental groups were found. Thus, the present study showed that infusion of a branched-chain amino acid-enriched solution improved nitrogen balance in septic rats. KIA alone or administered with the amino acid solution did not affect nitrogen balance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Infusion of a branched-chain amino acid-enriched solution and alpha-ketoisocaproic acid in septic rats: effects on nitrogen balance and skeletal muscle protein turnover. 339 21

Chronic sepsis is always associated with profound wasting leading to increased release of amino acids from skeletal muscle. Net protein catabolism may be due to decreased rate of synthesis, increased rate of degradation, or both. To determine whether protein synthesis is altered in chronic sepsis, the rate of protein synthesis in vivo was estimated by measuring the incorporation of [3H]-phenylalanine in skeletal muscle protein in a chronic (5-day) septic rat model induced by creation of a stable intra-abdominal abscess using an E. coli + B. fragilis-infected sterile fecal-agar pellet as foreign body nidus. Septic rats failed to gain weight at rates similar to control animals, therefore control animals were weight matched to the septic animals. The skeletal muscle protein content in septic animals was significantly reduced relative to control animals (0.18 +/- 0.01 vs. 0.21 +/- 0.01 mg protein/gm wet wt; p less than 0.02). The rate of incorporation of [3H]-phenylalanine into skeletal muscle protein from control animals was 39 +/- 4 nmole/gm wet wt/hr or a fractional synthetic rate of 5.2 +/- 0.5%/day. In contrast to control animals, the fractional synthetic rate in septic animals (2.6 +/- 0.2%/day) was reduced by 50% compared to control animals (p less than 0.005). The decreased rate of protein synthesis in sepsis was not due to an energy deficit, as high-energy phosphates and ATP/ADP ratio were not altered. This decrease in protein synthesis occurred even though septic animals consumed as much food as control animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of skeletal muscle protein synthesis in septic intra-abdominal abscess. 339 97

Sepsis has been shown to decrease skeletal muscle glucose oxidation by inhibiting the pyruvate dehydrogenase activity (PDHa) and to increase proteolysis and use of branched-chain amino acids (BCAA). The effects of dichloroacetate (DCA), which reverses PDHa inhibition, were studied in skeletal muscle from a septic (S) rat model of intra-abdominal abscess (E. coli + B. fragilis) and compared to control (C) and sterile inflammatory abscess (I) animals. In one set of S, I, and C animals, DCA (1 mmol/kg) was injected intraperitoneally at 0, 30, and 60 min. Septic, but not I, rats had a twofold increase in skeletal muscle lactate concentrations over C, but no changes in pyruvate. After DCA, both lactate and pyruvate were reduced (p less than 0.001) to same level in S, I, and C. Skeletal muscle alanine was increased in S compared to I or C, but after DCA was reduced threefold in C, S, and I (p less than 0.001) suggesting that alanine synthesis may be impaired due to decreased pyruvate availability. Like alanine, skeletal muscle BCAA were increased in S compared to C, but not altered in I. Following DCA, BCAA levels in muscle from S were reduced (p less than 0.001) to values seen in C or I. Muscle phenylalanine content was significantly elevated in S (p less than 0.05) compared to C or I, but was reduced (p less than 0.05) after DCA in S but not in C or I. Decreased muscle phenylalanine associated with lowered BCAA suggests DCA may decrease septic muscle protein catabolism and/or enhance protein synthesis. Coupled with an increased PDHa and reduced lactate levels, this suggests that DCA may reverse the excess muscle catabolism and BCAA dependence of sepsis by increasing glucose and lactate oxidation and may be a useful therapeutic modality.
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PMID:Pharmacological reversal of abnormal glucose regulation, BCAA utilization, and muscle catabolism in sepsis by dichloroacetate. 341 55

In 45 burn patients serum amino acids together with liver enzymes and other serum parameters were determined. Phe levels, Phe:Tyr and Phe:TAA ratios were correlated with the clinical course of the patient's condition. Based on empirical data, an increase in the Phe:TAA ratio of over 3% was found to be the best indicator of a critical period in the clinical course. An increase in the Phe:TAA ratio above 3% accompanied the signs of sepsis. If the patient recovered, the ratio decreased. Ratios which kept constant or even increased--indicating a possible fatal clinical outcome--were found to be alarming. In our experience Phe levels or Phe:Tyr ratios did not have indicative functions.
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PMID:Phenylalanine: total amino acid ratio in 45 burn patients. 344 59

Polymorphonuclear leukocyte (PMN) function was investigated in two patients with glycogen storage disease type IB and neutropenia. Glycogen storage disease type IB was documented by liver biopsy and a normal amount of latent glucose-6-phosphatase activity. Patient A had stomatitis, skin infections, and septicemia; patient B had respiratory infections, periodontitis, and oral candidiasis. Absolute neutrophil counts ranged from 114 to 2580/mm3. Diminished and delayed migration of PMN into a skin "window" occurred in B. Random and directed PMN migration under agarose toward f-Met-Leu-Phe, pepstatin A, and zymosan-activated serum were severely diminished in both patients. At 10(-7) M f-Met-Leu-Phe, mean random and directed migration were 52 and 23% (A, n = 3) and 48 and 13% (B, n = 4) of controls. These results were independent of incubation time and chemoattractant concentration. Patients' PMN had diminished quantitative nitroblue tetrazolium reduction compared to controls. B had a significant defect in PMN bactericidal activity with Escherichia coli with less than 0.2 log killing at 2 h. These results further characterize the defect in PMN migration reported by Beaudet et al. (J Pediatr 97:906, 1980). The finding of other abnormalities of PMN function suggests a metabolic defect in the neutrophil which may be related to the microsomal membrane defect in hepatocytes in glycogen storage disease type IB.
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PMID:Impaired chemotaxis and neutrophil (polymorphonuclear leukocyte) function in glycogenosis type IB. 345 31

Five days after thyroidectomy (Tx) or sham-Tx in young male Sprague-Dawley rats, sepsis was induced by cecal ligation and puncture (CLP). Control animals underwent laparotomy and manipulation of the cecum without ligation or puncture. Sixteen hours after CLP or laparotomy, protein synthesis and degradation were measured in incubated extensor digitorum longus (EDL) and soleus (SOL) muscles by determining rate of 14C-phenylalanine incorporation into protein and tyrosine release into incubation medium, respectively. Triiodothyronine (T3) was measured in serum and muscle tissue. Protein synthesis was reduced by 39% and 22% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx rats. The response to sepsis of protein synthesis was abolished in Tx rats. Protein breakdown was increased by 113% and 68% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx animals. The increase in muscle proteolysis during sepsis was blunted in hypothyroid animals and was 42% and 49% in EDL and SOL, respectively. T3 in serum was reduced by sepsis, both in Tx and sham-Tx rats. T3 in muscle, however, was maintained or increased during sepsis. Abolished or blunted response of muscle protein turnover after CLP in hypothyroid animals may reflect a role of thyroid hormones in altered muscle protein metabolism during sepsis. Reduced serum levels of T3, but maintained or increased muscle concentrations of the hormone, suggests that increased T3 uptake by muscle may be one mechanism of low T3 syndrome in sepsis, further supporting the concept of a role for thyroid hormone in metabolic alterations in muscle during sepsis.
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PMID:Studies on the possible role of thyroid hormone in altered muscle protein turnover during sepsis. 360 30

A series of patients with meningococcal infections have been studied and divided in two groups: Group I patients with meningococcal sepsis and group II, those with meningococcal meningitis. Patients in group I presented with more severe encephalopathy, shock, DIC and acute systemic complications. Both groups showed a marked hypoaminoacidemia compared with normal controls (other than for the sulfur containing amino acids and phenylalanine). The concentration of aromatic and basic amino acids, the phenylalanine/tyrosine ratio, the transaminase levels and the negative nitrogen balance were higher in group I patients. The ratio of branched chain to aromatic amino acids was lower in group I. All these differences were statistically significant. The close association between the metabolic derangements and clinical manifestations may help in the understanding of several physiopathological aspects of meningococcal infections.
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PMID:Significance of the changes in plasma amino-acid levels in meningococcal infection. 365 98

Protein synthesis and degradation rates were measured in incubated soleus (SOL) and extensor digitorum longus (EDL) muscles 4, 8, and 16 hours following cecal ligation and puncture (CLP) in rats. No significant differences in protein synthesis between septic and control rats were found. The proteolytic rate in SOL muscle was increased by 36% eight hours after CLP and by 42% 16 hours after CLP. In EDL muscle, protein breakdown was not significantly increased until 16 hours after CLP, at which time it was 53% above the control value. The plasma amino acid pattern became increasingly deranged during the course of the study, and at 16 hours almost all individual amino acid levels were significantly different in septic rats compared with control rats. There was a significant positive correlation between plasma concentrations of phenylalanine, histidine, and ornithine and the proteolytic rate in EDL and SOL muscles, with the best correlation being found between phenylalanine concentration and proteolytic rate in SOL muscle. These results suggest that muscle wasting during sepsis is caused by increased protein breakdown, not by decreased protein synthesis, and that accelerated muscle proteolysis is an early phenomenon in sepsis.
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PMID:Protein metabolism in different types of skeletal muscle during early and late sepsis in rats. 372 10

Previous studies indicate that endogenous chemotaxins, such as the chemotactic factor C5a, may modulate the function of neutrophils (PMNs) and account for increased susceptibility to infection after injury. These effects were investigated by continuously infusing rats with saline or the chemotaxin formyl-methionyl-leucyl-phenylalanine (FMLP). Rats that sustained a full-thickness burn covering 30% of total body surface area and whose wounds were inoculated with Pseudomonas aeruginosa had a significantly shorter survival when FMLP was infused (6.5 +/- 0.91 days) than did saline-infused rats (9.9 +/- 0.83 days). Rats infused with FMLP had significantly more leukocytes in their burn wounds, significantly fewer PMNs in the circulating pool, and the same number of PMNs at the site of FMLP infusion compared with the saline-treated group. These findings support the hypothesis that chemotaxins generated by tissue injury or sepsis contribute to increased susceptibility to infection.
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PMID:Increased susceptibility to infection due to infusion of exogenous chemotaxin. 380 Jun 43

To assess the mechanism and specificity of polymorphonuclear leukocyte (PMN) dysfunction induced by endotoxin, rabbits were injected intravenously with 100 micrograms of Escherichia coli endotoxin, and PMN function was studied 18 to 24 h later. Compared to PMN from normal rabbits, peripheral blood PMN from rabbits injected with endotoxin showed diminished chemotactic responsiveness to two endogenous peptides, C5a (complement) and platelet-derived growth factor, and to two endogenous lipids, leukotriene B4 and platelet-activating factor. The chemotactic response to the synthetic chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP), was unimpaired. In contrast to migration, endotoxin injection resulted in inhibition of the secretory response to the two endogenous peptides but not to the lipids or to FMLP. At a 1:4 (vol/vol) dilution, the plasma either 1 or 24 h after the endotoxin injection inhibited normal PMN chemotactic responses to C5a but not to FMLP. Similarly, at a 1:10 dilution, this plasma inhibited normal PMN chemotactic responses to leukotriene B4. The factor responsible for inhibiting responses to leukotriene B4 was anionic, specific for leukotriene B4 responses, and greater than 12,000 daltons. These data may be relevant to understanding PMN dysfunction during gram-negative sepsis.
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PMID:Endotoxin-induced selective dysfunction of rabbit polymorphonuclear leukocytes in response to endogenous chemotactic factors. 390 47


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