Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pulmonary dysfunction after cardiopulmonary bypass has been attributed to the damaging effects of complement activation on the lung. To further explore this phenomenon, we measured plasma levels of activated complement components (radioimmunoassay), assessed neutrophil n-formyl-methionyl-leucyl-phenylalanine (FMLP) receptor status (radioligand saturation binding assay), and quantified pulmonary epithelial permeability as radioaerosol lung clearance of technetium 99m-labeled diethylenetriamine pentaacetic acid in a series of 8 patients undergoing cardiopulmonary bypass. Significant elevations of plasma C3adesArg, C4adesArg, and C5adesArg levels were seen just after CPB, indicating activation of both the classic and alternate complement pathways. Neutrophil activation was evident as increased expression of neutrophil FMLP surface receptors after bypass. Despite the presence of complement and neutrophil activation, increased pulmonary epithelial permeability was not seen. These data support the hypothesis that complement and neutrophil activation during cardiopulmonary bypass is not associated with acute lung injury, at least not pulmonary epithelial injury. One can therefore infer that increased pulmonary epithelial permeability in patients at high risk for and experiencing sepsis-induced and trauma-induced adult respiratory distress syndrome may be due to factors other than complement and neutrophil activation.
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PMID:Complement activation and lung permeability during cardiopulmonary bypass. 201 41

We elected to test the hypothesis that the metabolic encephalopathy associated with systemic sepsis may have a pathogenesis that is similar to hepatic encepathology, ie, as the consequence of hepatic dysfunction that induces alterations in synthesis of catecholic and noncatecholic neurotransmitters. Eleven patients with septic encephalopathy were compared with nine patients with septic encephalopathy and nine normal controls with respect to blood and cerebrospinal fluid (CSF) amino acid profile, phenylethylamine and its metabolite phenylacetic acid, and blood ammonia. Blood and CSF levels of phenylacetic acid increased markedly in septic and hepatic encephalopathy while CSF phenylethylamine levels were not increased in either condition, presumably due to rapid turnover. The CSF concentrations of all the aromatic amino acids were increased in hepatic encephalopathy, whereas in the patients with sepsis, only phenylalanine levels were increased. Evidence of stimulated neutral amino acid transport into brain was demonstrated in hepatic not septic encephalopathy and appeared to correlate with the CSF glutamine concentration. Blood ammonia levels were increased in hepatic but not in septic encephalopathy. Our data support the hypothesis that metabolites of phenylethylamine contribute to encephalopathy in systemic sepsis and hepatic failure; however, the entities differ in other respects.
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PMID:Septic encephalopathy. Evidence for altered phenylalanine metabolism and comparison with hepatic encephalopathy. 230 19

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

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

Serum aminogram changes were prospectively studied in 95 patients with enteric fistula and intraabdominal infection who was under total parenteral nutrition (TPN) therapy with Anfuming 14s. In patients with sepsis and starvation, the aminogram showed remarkably low total free amino acids before TPN therapy. In 81 survivors, free amino acids increased gradually to normal in 2 weeks after use of TPN and in 14 dead cases increased rapidly to a significantly higher peak at terminal stage. Both in survivors and nonsurvivors, phenylalanine level remained high during the study. In response to infection, proline was also elevated but to a lesser degree; the ratio of branched chain amino acid (BCAA) to aromatic amino acid (AAA) was lower than normal and the decrease of arginine was parallel to the severity of infection. We conclude that the ideal amino acids preparation for the starvated and septic patients should be high in BCAA and arginine but low in phenylalanine, administration of inappropriate exogenous amino acids in decompensated metabolic septic patients may bring about more harm than benefit, and in septic patients that the levels of serum phenylalanine and proline are elevated persistently along with the decrease of arginine level is a useful prognostic indication.
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PMID:[Changes in serum amino acids in total parenteral nutrition supported patients with intra abdominal infection]. 251 49

Plasma aminogram changes were prospectively studied in 95 patients with external enteric fistula and intraabdominal infection who were under total parenteral nutrition (TPN) therapy with anfuming 14s. Plasma amino acids and albumin were determined before the administration of TPN, weekly and at the end of the therapy or 2 to 5 days before death of patients. In patients with sepsis and starvation, the aminogram showed remarkably low total free amino acids before TPN therapy. In survivors, free amino acids increased gradually to normal in 2 weeks after use of TPN and in the dead increased rapidly to a significantly high peak at the terminal stage. In both survivors and deceased, phenylalanine level remained high during the study. In response to infection, proline was also elevated but to a lesser degree; the ratio of branched chain amino acid (BCAA) to aromatic amino acid (AAA) was lower than normal and the decrease of arginine was parallel to the severity of infection. We conclude that the ideal amino acid preparation for the starved, septic patients should be high in BCAA and arginine but low in phenylalanine; the administration of inappropriate exogenous amino acids in metabolically decompensated septic patients may bring about more harm than benefit; and in septic patients the persistently elevated level of plasma phenylalanine and proline along with decrease of arginine is a useful prognostic sign.
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PMID:Changes of plasma amino acids in total parenteral nutrition-supported patients with intraabdominal infection. 251 37

We have shown previously that fluid phase platelet-activating factor (PAF) can enhance or "prime" polymorphonuclear (PMN) responses to subsequent stimulation with agonists such as formyl-methionine-leucine-phenylalanine (FMLP). Since thrombin induces PAF production in endothelial cells, we tested whether this thrombin-provoked endothelial PAF primes responses of marginated PMNs. Monolayers of human umbilical vein endothelial cells were exposed to either thrombin (0.5-5.0 units/ml) or buffer for up to 5 min and then PMNs were layered on top of the endothelial cells. After a further 5 min incubation, the PMNs were stimulated with a suboptimal concentration of FMLP (10(-7) M), and their superoxide production, elastase release, adhesion to endothelium, and capacity to cause endothelial cell lysis and detachment were assessed. Thrombin pretreatment significantly enhanced each of these FMLP-stimulated neutrophil responses. The extent of this enhancement correlated with both the dose and duration of thrombin treatment of endothelial cells and also the duration of PMN incubation with thrombin-exposed endothelium. Evidence that the augmentation was due to endothelial-derived PAF was obtained as follows: (1) thrombin induced [3H]acetate incorporation into endothelial PAF (assayed in lipid extracts); (2) antithrombin III conjointly inhibited this [3H]acetate uptake and prevented the priming effect of thrombin-treated endothelium on PMN responses; and (3) the PAF receptor antagonist BN52021, when preincubated with PMNs, also effectively blocked the enhancement of PMN responses. We conclude that thrombin stimulation of endothelial cells initiates a sequence of events culminating in the production of PAF--a membrane phospholipid capable of priming marginated PMNs. We suggest that this coagulation-fostered endothelial/PMN interaction may underlie a paracrine response that may potentiate PMN-mediated endothelial injury during sepsis and other thrombin-generating disorders.
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PMID:Thrombin-treated endothelium primes neutrophil functions: inhibition by platelet-activating factor receptor antagonists. 254 22

The effect of sterile inflammation and sepsis on the release of lactate and amino acids by peripheral tissues was investigated in rats by removing the splanchnic organs (liver + small intestines) from the circulation and monitoring changes in blood metabolites over 30 min. Functional hepatectomy was performed in rats 5-7 days following the intraperitoneal introduction of a fecal-agar pellet (sterile vs. Bacteroides fragilis + E. coli). Lactate was significantly (P less than .05) increased in each of the conditions following hepatectomy but was raised to a significantly greater extent in sepsis (P less than .05). A similar response was observed for glutamine while alanine was only significantly (P less than .05) increased in sepsis following hepatectomy. Branched chain amino acids (BCAA) showed differential changes in sepsis compared to control. In control and sterile inflammation, functional hepatectomy was associated with significant decreases (P less than .05) in BCAA. In sepsis, BCAA were not decreased following hepatectomy and were significantly (P less than .05) elevated relative to control or sterile inflammation. Phenylalanine concentrations were not altered in control or sterile inflammation but were significantly elevated in sepsis (P less than .05). Insulin attenuated the accumulation of lactate and amino acids in fed control animals, following functional hepatectomy. However, in septic animals, insulin failed to prevent the rise in plasma lactate following hepatectomy.
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PMID:Role of extra-splanchnic organs in the metabolic response to sepsis: effect of insulin. 267 32

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

Production of superoxide anion by polymorphonuclear leukocytes (PMNL) was studied in donors and patients with burns. N-formyl-L-Met-L-Leu-L-Phe (FMLP) was used as an activator of PMNL. Evaluation in production of superoxide anion, caused by the activating effect of FMLP, proved to be useful as a diagnostic and prognostic criterion. 56 preparations of blood were studied in 21 patients with burns within the periods of acute burns toxemia, burns septicotoxemia and convalescence. Superoxide anion generating activity correlated with the disease severity: content of superoxide anion was distinctly decreased within the period of sepsis development. At the same time, complex treatment of the patients, involving step-by-step autodermoplastics, antibacterial preparations and immunotherapy, enabled to restore the superoxide anion production up to normal values. Evaluation of the superoxide anion generating activity by PMNL in the patients with severe forms of burns enabled to estimate the state of cell immunity in the patients depending on severity of burns trauma, period of burn disease and adequacy of the treatment applied.
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PMID:[Enzymatic production of superoxide by human polymorphonuclear leukocytes in burns]. 285 Dec 10


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