Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.37 (neutrophil elastase)
 4,078 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a rhesus monkey endotoxin sepsis model established by intravenous administration of 300 mg/kg D-galactosamine and 0.1 microgram/kg lipopolysaccharide from Salmonella abortus equi, hemodynamic, respiratory, metabolic and hematologic variables; levels of blood gases; monkey leukocyte elastase levels, and blood plasma concentrations of tumor necrosis factor--alpha (TNF) were monitored for 6 hours after administration, and again after 24 hours. Thirty minutes after administration of lipopolysaccharide, either 15 mg/kg anti-TNF monoclonal antibody (MoAB; n = 6) or vehicle placebo (saline solution; n = 4) were given intravenously. During this short-term experiment the organ functions were not different between the treatment groups. However, anti-TNF MoAb afforded morphologic protection from heart, lung, liver, and kidney damage after lipopolysaccharide challenge. Coagulation responses (platelet count and levels of fibrinogen, antithrombin III, and thrombin-antithrombin III complex) were smaller in anti-TNF MoAB-treated monkeys. Plasma TNF levels (WEHI cell cytotoxicity assay) reached a peak (350 pg/ml) 60 minutes after lipopolysaccharide administration in vehicle control subjects but no TNF was detected in the anti-TNF MoAB-treated monkeys. All control animals died 67 +/- 30 hours after lipopolysaccharide administration from multiorgan failure. On the contrary, all anti-TNF MoAB-treated animals survived 14 days (p > 0.005 vs placebo group mortality). Thus in short-term monkey experiments our study indicates protection against lipopolysaccharide-induced endotoxin sepsis by anti-TNF MoAB, which may have clinical relevance for the treatment of human septicemia.
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PMID:Monoclonal antibody to tumor necrosis factor--alpha prevents lethal endotoxin sepsis in adult rhesus monkeys. 140 33

We studied the effect of aminosugars on the elastase enzyme released from cytochalasin-B treated polymorphonuclear neutrophils (PMN) and stimulated by F-Met-Leu-Phe (FMLP). Both N-acetyl-galactosamine and N-acetyl-glucosamine can inhibit the release of leukocyte elastase enzyme. N-acetyl-galactosamine was a potent inhibitor of elastase enzyme release in a dose-related fashion. Inhibition ranged from 91.9% up to total inhibition. N-acetyl-glucosamine showed a mild inhibitory effect on elastase enzyme release; however, it too acted in a dose-related fashion. The range of inhibition was 17.17%-8.18%. Mannosamine showed an inhibitory effect in some donors, but this effect was not statistically significant. No effect on elastase enzyme release was shown with other sugars such as D-glucose and L-fucose. These results show that N-acetyl-galactosamine can inhibit the respiratory burst, which suggests that the aminosugars might do more than interfere with the carbohydrate lectin interaction.
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PMID:Inhibition of elastase enzyme release from human polymorphonuclear leukocytes by N-acetyl-galactosamine and N-acetyl-glucosamine. 205 63

The changes in plasma concentrations of reduced glutathione were investigated in rats with endotoxin hepatitis. An increase in serum alanine aminotransferase activity and in serum total bilirubin concentration was observed 12 hr after the intraperitoneal co-administration of small doses of Escherichia coli lipopolysaccharide and D-galactosamine in starved rats. At the same time, an increase in the plasma concentration of reduced glutathione was also observed. The increase in reduced glutathione from 14 +/- 2 to 20 +/- 9 microM (n = 11, P < 0.05) correlated well with that in serum alanine aminotransferase activity. Ulinastatin, a potent inhibitor of polymorphonuclear leukocyte elastase, partially counteracted all of these changes. Ulinastatin also reduced histological liver damage induced by endotoxin. We conclude that the increase in the plasma concentration of reduced glutathione reflects hepatocellular damage associated with endotoxin hepatitis. The partial reversal of the damage by ulinastatin is consistent with the proposal that the activation of polymorphonuclear leukocytes is involved in endotoxin hepatitis.
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PMID:Increase in the plasma concentration of reduced glutathione observed in rats with liver damage induced by lipopolysaccharide/D-galactosamine: effects of ulinastatin, a urinary trypsin inhibitor. 814 54

Several samples of oversulfated chondroitin and dermatan were obtained by chemical sulfation and by SAX-HPLC enrichment. The starting products and oversulfated products were tested as potential inhibitors of human leukocyte elastase, an enzyme hypothesized to be involved in the etiology of diseases such as emphysema, atherosclerosis, and rheumatoid arthritis. Chemical oversulfation (SO3H/COOH 1.6-3.2), preferentially occurring at C-6 of galactosamine residues, was found generally to increase the inhibitory power on elastase. Chemically oversulfated galactosaminoglycans thus have potential as therapeutic agents, considering that they produce non-significant effects on the hemocoagulative system. Two naturally oversulfated dermatans sulfate (SO3H/COOH ca. 1.2), mainly oversulfated at C-2 of iduronic acid residues, showed comparatively higher anticoagulant activity (in the HC-II mediated thrombin inhibition test).
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PMID:Inhibition of human leukocyte elastase by chemically and naturally oversulfated galactosaminoglycans. 854 7

A series of peptide-based transition-state human neutrophil elastase (HNE) inhibitors with N-terminal acidic moieties were synthesized and their inhibitory activity against HNE was evaluated both in vitro and in vivo. Our results show that compounds containing cyclic amide bridged acidic moieties at the N-terminal have not only improved water solubility but also high in vivo potency. Among these compounds, AE-3763 showed remarkable efficacy in hamster models of elastase-induced lung hemorrhage and lipopolysaccharide (LPS)-induced lung injury as well as in a mouse model of LPS/galactosamine-induced acute multiple organ dysfunctions. The water solubility of AE-3763 (>1000 mg/ml in H(2)O) was also far superior to that of any of the other compounds synthesized. Thus, it is believed that AE-3763 would be useful for treatment of HNE-associated respiratory disorders, such as acute respiratory distress syndrome (ARDS), acute lung injury (ALI), and acute exacerbation of chronic obstructive pulmonary disease (COPD).
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PMID:Development of a highly water-soluble peptide-based human neutrophil elastase inhibitor; AE-3763 for treatment of acute organ injury. 1981 24