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

In adults supplemental parenteral nutrition (PN) is advisable in burns over 40% especially when weight loss exceeds 10% of body weight. In children with smaller reserves and higher requirement of proteins and energy no rigid scheme for parenteral supplementation is used at our unit. In a young infant it may be added already at a 20-30% deep burn, especially with connected gastrointestinal tract problems, infection etc. Metabolic and protein requirements are estimated 50-100% in addition to their normal needs. Hypertonic glucose (gradually increased from 20-40%), covered with insulin in the early phase, is used as source of carbohydrates. L-amino acid mixture containing the "pediatric essential amino acids" histidine and cysteine is given as a nitrogen source. 20% Intralipid is given in a gradually increased amount of 2-4 g/kg per day to provide calories and essential fatty acids. Among electrolytes K, Ca, P and Mg must be added. Increased amounts of vitamin C and folate are needed by burned children. Vitamin E is also required during prolonged lipid administration. Trace elements (Zn. Fe, etc.) are supplied orally or i.v. with special solutions or fresh plasma infusions. Our experience with parenteral nutrition in severely burned children will be presented. There were no severe metabolic side-effects but sepsis represented the major problem. The concomitant heat preservation by warming the room and use of infra-red heaters is emphasized.
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PMID:Parenteral nutrition in severely burned children. 10 12

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

There is considerable evidence to implicate aggressive species of oxygen in the pathogenesis of organ dysfunction consequent to sepsis and septic shock. The inflammatory process appears to participate ubiquitously in this setting. A characteristic of inflammation is the involvement of activated neutrophils and their generation of aggressive oxygen species. Such species may both directly injure cells proximal to the oxidant generating cells, and may inactivate any proteolytic mechanisms normally protective against proteolytic injury caused by neutrophil elastase and other proteolytic enzymes released during inflammation. The offending agent in sepsis is most commonly envisioned as bacterial lipopolysaccharide, or endotoxin. Infusion of endotoxin into animals can reproduce much of the pathophysiology of sepsis and septic shock. In addition, administration of endotoxin to cultured cells, particularly endothelial cells, can cause responses consistent with a sequence of events that occurs in intact animals and humans. In both experimental models, it appears that aggressive oxygen species are important actors in the scenario eventuating in cell or organ injury. Of importance, the toxic consequences of these free radicals probably occurs in relatively protected spaces, including microenvironments created by close adherence between inflammatory cells and endothelial cells and the cell interior. For those reasons, the potential for antioxidants as therapy should include consideration of the volume of distribution of such substances. It is probably important that antioxidants access excluded spaces including cell interiors in order to have their maximum effect in this setting. We have studied ina preliminary way the effects of n-acetyl-cysteine, a highly permeable free radical scavenger and anti-oxidant, in patients with established ARDS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxygen radicals--an important mediator of sepsis and septic shock. 179 73

The response to injury and infection can be viewed as a mobilization of body protein, fat, and carbohydrate stores to ensure normal or above-normal circulating levels of substrate in the absence of dietary intake. The situation does not readily yield to nutritional manipulation, and inappropriate nutritional support can cause additional stress. Artificial nutrition is mainly a form of nutrient administration and not nutrient utilization. Modulation of neurohumoral and wound responses to trauma due to starvation and refeeding has not been delineated. The provision of adequate substrates alone does not necessarily guarantee their efficient use in metabolism. With a clear knowledge of the role of cellular mediators in the pathophysiology of disease, it may be possible to develop more rational therapeutic approaches during critical illness. Determination of appropriate and optimal substrate support through parenteral and enteral nutrition remains of great clinical importance. The clinical application of branched-chain amino acids, dispensable amino acids, acetylated amino acids, dipeptides or tripeptides, cysteine, glutamine, and arginine has been explored in recent years. The idea that lipids are deleterious in sepsis and organ failure should be revised and documented, and recent studies suggest that fish oils as a lipid source may also favorably affect immune responses. Under stressful conditions, total parenteral nutrition can require large amounts of energy at a time when there are marked disturbances in glucose utilization. In this area, the use of nonglucose carbohydrates or oligosaccharides can be appropriate, despite the lack of broad acceptance. Existing conventional substrates should be studied beyond mere provision of energy and metabolic pathway support.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nutritional and metabolic support: converging concepts. 180 4

Pseudomonas aeruginosa alkaline proteinase, which is a zinc-dependent bacterial endopeptidase, preferentially hydrolyzed Boc-Val-Leu-Lys-methylcoumarylamide (MCA) which was originally designed as a specific substrate of plasmin, a plasma serine proteinase. The hydrolytic capacity was resistant to tosyl-lysine chloromethylketone at a concentration as high as 1 mM, but was blocked by a treatment with metal chelator such as o-phenanthroline at the concentration of 5 mM. Kinetic parameters of the amidolytic reaction were Km = 21 microM, kcat = 0.067 s-1 and kcat/Km = 3190 M-1 s-1. A synthetic peptide inhibitor which bore a possible ligand for zinc atom at the carboxy terminal was designed. This inhibitor, Ac-Val-Leu-Lys-4-mercaptoanilide, blocked the amidolytic activity of the pseudomonal alkaline proteinase in a competitive manner with the dissociation constant (Ki) value of 24 microM. The results imply that P. aeruginosa alkaline proteinase must be an unusual zinc-dependent 'C (COOH)-type' endopeptidase, which hydrolyzes the peptide bond of certain amino acid residues at the carboxyl group side by specific recognition, like serine- and cysteine-proteinases. In comparison, P. aeruginosa elastase which is a typical 'N (NH2)-type' metalloproteinase did not hydrolyze all of the commercially available peptide-MCA substrates tested at the present study. P. aeruginosa alkaline proteinase also hydrolyzed natural substrates of plasmin, such as fibrin and fibrinogen, with similar specific activities to plasmin. The susceptible subunits of fibrinogen were the A-alpha and B-beta ones, in this order. P. aeruginosa alkaline proteinase also exhibited an anti-coagulant activity in human plasma attributed to the direct fibrinogenolytic function. Such potential anti-coagulant capacity of the P. aeruginosa alkaline proteinase might explain, at least partly, the most characteristic pathologic feature of the P. aeruginosa septicemia, hemorrhagic lesions with lacking thrombi (Fetzer, A.E. et al. (1967) Am. Rev. Respirat. Dis. 96, 1121-1130).
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PMID:Pseudomonas aeruginosa alkaline proteinase might share a biological function with plasmin. 182 96

Vibrio anguillarum is a pathogenic marine bacterium which causes the disease vibriosis in salmonid fish, which is characterized by a fatal hemorrhagic septicemia accompanied by massive tissue destruction. In this paper, the purification of the major caseinolytic extracellular protease from V. anguillarum is presented. The purification steps include ammonium sulfate precipitation, DEAE-Sepharose chromatography, Sephacryl S-200 chromatography, and DEAE high-pressure liquid chromatography. The purified protease migrates with Mr = 38,000 upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A slightly larger protease of Mr 40,000 is also separated by this procedure, but accounts for only a minor fraction of the caseinolytic activity. The Mr 38,000 protease displays a broad pH activity profile in the neutral to basic range. It is not inhibited by serine, cysteine, or acid protease inhibitors, but is inhibited by EDTA and 1,10-phenanthroline, suggesting that it is a metalloprotease. The activity of the EDTA-inactivated protease could be partially restored by the addition of Ca2+ and Zn2+ together. The molecular weight and inhibition data show some similarities with proteases isolated from other Vibrio species such as Vibrio cholerae and Vibrio vulnificus.
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PMID:Purification and characterization of a secreted protease from the pathogenic marine bacterium Vibrio anguillarum. 201 4

A case of septicemia and urinary tract infection caused by cysteine-dependent Escherichia coli in a 70-year-old woman with bilateral staghorn calculi is described. This is the second report of a cysteine-dependent E. coli bacteremia. The bacterium was falsely susceptible to ampicillin and co-trimoxazole when tested on a medium without cysteine supplement.
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PMID:Septicemia caused by cysteine-dependent Escherichia coli. 219 Oct 4

High molecular weight kininogen (HMWK) is a multifunctional protein that is a parent molecule for bradykinin, a cofactor for coagulation, and an inhibitor of cysteine proteases. On immunoblot, nonreduced plasma HMWK is usually two bands at 140 kd and 120 kd; reduced plasma HMWK is a single band at 120 kd. In both concentration-dependent and time-dependent experiments kaolin-activated normal plasma HMWK becomes cleaved in an ordered sequence. When nonreduced, HMWK on immunoblot in kaolin-activated plasma changes in size from a 140 kd band through a 120 kd intermediate to result in a stable 100 kd protein. When reduced, HMWK on immunoblot in kaolin-activated plasma changes from a single 120 kd band through a 56 kd intermediate to result in a stable 46 kd protein. A similar sequence of cleavage of plasma HMWK occurs when the soluble activator dextran sulfate is used to stimulate the system. Cleavage of plasma HMWK after kaolin activation occurs similarly in factor XI-deficient plasma as in normal plasma but is decreased in prekallikrein-deficient plasma. Prolonged kaolin activation of prekallikrein-deficient plasma results in HMWK cleavage to bands below 120 kd. No band of plasma HMWK below 120 kd appears in prolonged kaolin-activated factor XII-deficient plasma. In some patients with sepsis, detectable cleavage of plasma HMWK to bands below 120 kd may not be seen, even though the patient has other evidence for contact system activation. In conclusion, these studies indicate that certain cleaved patterns of plasma HMWK on immunoblot indicate prior activation of the contact system. However, the absence of these cleaved forms of plasma HMWK in a single plasma does not exclude the occurrence of contact activation.
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PMID:Structural changes of plasma high molecular weight kininogen after in vitro activation and in sepsis. 245 60

Staphylococcus aureus is known to produce three very active extracellular proteinases. One of these enzymes, a cysteine proteinase, after purification to homogeneity was found to degrade insoluble bovine lung elastin at a rate comparable to human neutrophil elastase. This enzyme had no detectable activity against a range of synthetic substrates normally utilized by elastase, chymotrypsin, or trypsin-like proteinases. However, it did hydrolyze the synthetic substrate carbobenzoxy-phenylalanyl-leucyl-glutamyl-p-nitroanilide (Km = 0.5 mM, kcat = 0.16 s-1). The proteolytic activity of the cysteine proteinase was rapidly and efficiently inhibited by alpha 2-macroglobulin and also by the cysteine-specific inhibitor rat T-kininogen (Ki = 5.2 X 10(-7) M). Human kininogens, however, did not inhibit. Human plasma apparently contains other inhibitors of this enzyme, since plasma depleted of alpha 2-macroglobulin retained significant inhibitory capacity. The elastolytic activity of this S. aureus proteinase and its lack of control by human kininogens or cystatin C may explain some of the connective tissue destruction seen in bacterial infections due to this and related organisms such as may occur in septicemia, septic arthritis, and otitis.
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PMID:Degradation of elastin by a cysteine proteinase from Staphylococcus aureus. 342 37

Proteinases are classified into four groups according to their catalytic mechanisms: the serine, cysteine (thiol), aspartic (carboxyl), and metallo-proteinases. Neutrophil granulocytes contain a variety of neutral proteinases and two acid proteinases. Lysosomal proteinases are released from cells during phagocytosis, cell death, or exposure to antigen-antibody complexes, complement factors, and toxins. Under pathological conditions, massive proteinase release may cause tissue injury and degradation of plasma proteins. Plasma proteolytic activity is controlled by inhibitors of blood systems (antithrombin III, C1 inhibitor, and plasmin inhibitor) and by inhibitors against proteinases of various body cells (alpha 1-proteinase inhibitor, alpha 1-antichymotrypsin, beta 1-collagenase inhibitor, and inter-alpha-trypsin inhibitor). Intracellular proteinases are controlled by different cytosolic inhibitors. In hypercatabolic states (septicemia, trauma, burns), the concentrations of many plasma proteins, including proteinase inhibitors, are decreased. Kallikrein-kinin, complement, and fibrinolytic systems may be activated, probably due to enhanced proteinase activity. In acute renal failure, there is a release of granulocyte neutral proteinases. The plasma concentration of the elastase-alpha 1-proteinase inhibitor complex is simultaneously increased. Granulocytes of chronically uremic patients treated with diet or regular dialysis have a slightly to markedly reduced proteinase content as compared with normal controls. There is a dramatic rise of the plasma elastase alpha 1-proteinase inhibitor complex during hemodialysis treatment.
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PMID:Proteolytic enzymes and catabolism: enhanced release of granulocyte proteinases in uremic intoxication and during hemodialysis. 637 17


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