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)

Degranulation of polymorphonuclear granulocytes following minor surgery and the contributory role of temporary tissue ischaemia in a limb were examined in 22 otherwise healthy patients undergoing elective arthroscopy under general anaesthesia with and without tourniquet. Apart from an increase in lactate levels following tourniquet release there was no difference in complement split product C3d, cortisol, leukocyte or creatinine kinase levels between the two groups. There was a post-operative increase in the plasma E alpha 1-proteinase inhibitor concentration, whereas lactoferrin values decreased 4 h following tourniquet deflation. Anaesthesia and minor surgery are followed by post-operative release of polymorphonuclear neutrophil elastase. This release is not related to complement activation and is apparently unaffected by 50 min of lower limb ischaemia. Anaesthesia and minor surgery do not cause lactoferrin release.
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PMID:The influence of tourniquet ischaemia on post-operative degranulation of polymorphonuclear granulocytes. 160 Sep 73

Effect of serine protease inhibitor Camostat Mesilate (Foipan) on primary glomerulonephritis and it's mechanism were evaluated. Forty-two patients having primary glomerulonephritis (13 cases of IgA nephropathy, 11 cases of membranous nephropathy and others), aged 18 to 81 years were selected for this study. At the start of our study, twenty-one patients had received other drugs (13 cases of dipyridamole and 13 cases of prednisolone). A control period of four weeks was established to confirm that the levels of proteinuria and renal functions were stable. Patients were orally administered with 600 mg of Camostat Mesilate per day for four weeks. Effect of Camostat Mesilate was judged by urinary protein excretion, hematuria, serum total protein, albumin, Ccr, creatinine and BUN. In order to reveal the mechanism of the effect laboratory data such as granulocyte elastase, CH50, C3, C4, fibrinogen, platelate factor 4, beta-thromboglobulin, thromboxane B2 and prostaglandin F1 alpha were evaluated before and after the treatment. Parameters were analyzed by using paired t-test. Mean (+/- SEM) urinary protein excretion reduced from 4.31 +/- 0.91 to 2.80 +/- 0.43 g/day (p less than 0.05), and score of hematuria decreased from 1.8 +/- 0.16 to 1.5 +/- 0.15. A significant decrease in urinary protein excretion was seen in membranous nephropathy and a significant decrease in hematuria was seen in IgA nephropathy. In combination therapy (dipyridamole, prednisolone) urinary protein excretion markedly decreased (p less than 0.05) and in Camostat Mesilate therapy score of hematuria markedly decreased (p less than 0.05). Camostat Mesilate had no effects on renal function assessed by Ccr, creatinine and BUN.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of protease inhibitor on primary glomerulonephritis and the mechanism of the effect]. 177 Jun 35

In 42 patients with septic shock, 29 of whom underwent substitution with antithrombin III concentrate and fresh frozen plasma for coagulation disorders, the proteinase-inhibitor complexes thrombin-antithrombin III and neutrophil elastase-alpha 1 proteinase inhibitor, were elevated on admission. On admission, the elastase complex was significantly higher in the patients receiving substitution (p = 0.0039), but at the endpoint it was higher in the non-survivors (p = 0.0040). The elastase decrease was confined to the substitution group with the thrombin complex decreasing in both groups. Initially the thrombin complex correlated with prothrombin times and factor XIII, while the elastase complex correlated with creatinine, thrombocyte count and prothrombin times in the late stages. Hemostatic disturbance, thrombin generation and neutrophil elastase release were favorably influenced by substitution. Furthermore, in this uncontrolled pilot study, the survival rate was higher in the treated (16 of 29) than in the untreated (1 of 13) patients, although the treated patients initially had pronounced hemostatic disturbances.
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PMID:The disturbance of hemostasis in septic shock: role of neutrophil elastase and thrombin, effects of antithrombin III and plasma substitution. 278 82

Elastin degradation has been reported to be increased in patients with cystic fibrosis (CF). In order to further explore evidence for elastin degradation in a group of 18 patients with CF with a wide range of disease severity, we used an isotope dilution method to measure urinary desmosine (DES) and isodesmosine (IDES), amino acids derived exclusively from cross-linked elastin, and hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), amino acids derived exclusively from cross-linked collagen. Urinary DES and IDES (mean +/- SD) were 23.9 +/- 30.7 and 18.5 +/- 22.4 micrograms/g creatinine, respectively, in the patients with CF versus 7.5 +/- 1.7 and 6.8 +/- 1.4 micrograms/g creatinine, respectively, in 10 healthy control subjects (p < 0.001); only two patients with CF had DES values within the control range. The values of urinary HP and LP in the CF group were 54.9 +/- 39.1 and 12.3 +/- 8.6 nmol/mmol creatinine, respectively, versus 24.5 +/- 5.8 and 5.1 +/- 2.7 nmol/mmol creatinine, respectively, in the controls (p < 0.005). Both HP and LP were highly correlated (r = 0.71, p < 0.0001). Patients with CF had active pulmonary inflammation; neutrophils were abundant in the bronchoalveolar lavage fluid of the CF group and correlated with elastase activity measured with methoxysuccinyl Ala-Ala-Pro-Val paranitroanilide (r = 0.61, p < 0.05). Airway neutrophils had decreased expression of the complement receptor CR1 (CR1/CR3 of 0.17 +/- 0.15 versus 1.0 for blood neutrophils), a change known to be caused by uninhibited neutrophil elastase. We conclude that lung elastin is the most likely source of the increased DES and IDES in CF.
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PMID:Elastin and collagen degradation products in urine of patients with cystic fibrosis. 759 16

The purpose of this study was to evaluate the influence of ulinastatin (UST) on renal function and changes in granulocyte elastase during anesthesia in 10 living related and 10 cadaveric renal transplantations. UST (300,000 units) was administered after the induction of anesthesia and renal vessel anastomosis, respectively. The living patients who received UST had greater urine volume during the operative and postoperative periods. In addition, the granulocyte elastase values of these patients showed relative suppressive changes during the intraoperative and postoperative periods. In cadaveric renal transplant patients, UST did not influence serum BUN or creatinine, although urine volume was greater in the UST-treated patients than in the patients who did not receive. We could not conclude that the intraoperative administration of UST affected the renal function of renal transplants, but we did find that UST is useful to suppress granulocyte elastase which is concerned with the index of stress or inflammation. It is necessary to investigate further the method of administration of UST for renal transplantation.
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PMID:[The influence of ulinastatin on renal function during anesthesia for renal transplantation]. 818 15

The objective of this study was to determine the role of surgical procedures as secondary inflammatory insults in the development of late multiple organ dysfunction syndrome in patients with multiple trauma and to evaluate both specific and nonspecific indicators of the inflammatory response in their ability to indicate the risk of severely injured patients to develop organ failure after secondary operations. In a prospective study of 106 severely injured patients (ISS 40.6) who underwent secondary operations (> 3 days after trauma), we compared the level of preoperative inflammation with the sequelae of surgical trauma. The interventions included facial reconstructions; osteosynthesis of the pelvic girdle, long bones, and spine; and others. Group 1 consisted of 40 patients (38%) who developed respiratory, renal, or hepatic failure, or combinations thereof, within 2 days after the operation or whose preexisting organ dysfunction worsened by more than 20% from baseline. The remaining 66 patients (62%) with an uneventful recovery formed group 2. The preoperative levels of neutrophil elastase (92.2 vs. 61.3 ng/dL), C-reactive protein (12.4 vs. 7.6 mg/dL), and platelet count (118,000 vs. 236,000/microL) were significantly more abnormal in the patients of group 1. PO2/FiO2 ratio was also somewhat lower in group 1 patients (305.5 vs. 351), whereas other parameters (e.g., blood pressure, heart rate, bilirubin, creatinine, urinary output, lactate, pH, and coagulation) did not allow preoperative differentiation between groups 1 and 2. An increased state of inflammation (neutrophil elastase > 85 ng/mL, C-reactive protein > 11 mg/dL, platelet count < 180,000/microL) predicted postoperative organ failure with an accuracy of 79% (sensitivity, 73%; specificity, 83%). We conclude that secondary operations may act as a second insult and may precipitate late multiple organ dysfunction syndrome if they are performed in patients with multiple trauma while they still have an increased level of posttraumatic inflammation. However, future investigations have to show whether postponing surgery until inflammation has subsided or the use of less invasive surgical techniques will decrease the rate of postoperative organ failure in the trauma patient.
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PMID:Posttraumatic inflammatory response, secondary operations, and late multiple organ failure. 861 44

A severe acute pancreatitis was produced by intraperitoneal injection of lipopolysaccharide (LPS) in rats with preexisting hemorrhagic and necrotizing pancreatitis induced by retrograde injection of a 5% taurocholate plus 1% trypsin solution into the pancreatic duct. Mortality and time-course changes in pancreatic, hepatic, renal and pulmonary functions, and organ myeloperoxidase (MPO) levels were examined in this model. LPS at an intraperitoneal dose of 30 mg/kg, which scarcely caused death and had no marked effect on serum parameters and organ MPO levels in rats without pancreatitis, increased the mortality in rats with taurocholate plus trypsin-induced pancreatitis. Pancreatic weight and ascitic volume increased in rats with taurocholate plus trypsin-induced pancreatitis regardless of the presence or absence of LPS. Serum amylase and lipase levels were also significantly increased in rats with induced pancreatitis, but was higher in the group given LPS. Serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN) and creatinine levels were significantly elevated in LPS-treated rats with induced pancreatitis, whereas levels in rats with induced pancreatitis not given LPS were only slightly elevated. Renal weight was also significantly increased in rats with induced pancreatitis despite the presence or absence of LPS. In LPS-treated rats with induced pancreatitis, the arterial oxygen pressure, pulmonary weight and pulmonary MPO level were significantly elevated. However, the MPO level in the kidney in these rats was not different from that in control rats, indicating that the renal dysfunction was not produced by the infiltration of neutrophils into the kidney. Increase in the pancreatic MPO level was observed in rats with induced pancreatitis, but combination treatment with LPS did not raise it. Protective effects of prophylactic treatment of 2-(3-methylsulfonylamino-2-oxo-6-phenyl-1,2-dihydro-1-pyridyl)-N-( 3,3,3-trifluoro-1-isopropyl-2-oxopropyl)acetamide (compound 1), a neutrophil elastase inhibitor, and trifluoroacetyl-L-lysyl-L-alaninanilide hydrochloride (compound 2), a pancreatic elastase inhibitor, on mortality were also examined in this model. Results were compared with that of the combined treatment of compound 1 and compound 2. In LPS-treated rats with taurocholate plus trypsin-induced pancreatitis, the combined treatment of compound 1 (2 mg/kg/h) and compound 2 (30 mg/kg/h) significantly reduced mortality, whereas single treatment of compound 1 or compound 2 did not show the beneficial effect. These results suggest that marked hepatic and renal dysfunction accompanies pancreatitis in this pancreatitis model rats, which may be good models for acute pancreatitis in humans. It is also suggested that neutrophil and pancreatic elastases may be synergistically involved in the pathogenesis of acute pancreatitis in this model.
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PMID:Protective effect of the combined treatment of pancreatic and neutrophil elastase inhibitors on acute pancreatitis elicited by lipopolysaccharide in rats given intraductal injection of taurocholate plus trypsin. 965 Aug 10

The inhibitory effects of YM264, a selective platelet activating factor (PAF) receptor antagonist, and 2-(3-methylsulfonylamino-2-oxo-6-phenyl-1,2-dihydro-1-pyridyl)-N-( 3,3,3-trifluoro-1-isopropyl-2-oxopropyl)acetamide (compound 1), a neutrophil elastase inhibitor, on mortality, and pancreatic, hepatic, renal and pulmonary dysfunction were evaluated in a rat model of multiple organ failure (MOF) accompanying acute pancreatitis. MOF was produced by intraperitoneal injection of lipopolysaccharide (LPS, 30 mg/kg) in rats with cerulein-induced pancreatitis. LPS dose-dependently increased the mortality in rats with or without pancreatitis. The threshold dose which produced death in rats without pancreatitis was 30 mg/kg. This same dose evoked death in more than 40% of rats with pancreatitis. Time-course changes in serum enzyme and organ myeloperoxidase (MPO) levels were first examined in rats with induced MOF, and the results were compared with those in rats treated with only LPS or cerulein. Pancreatic weight, and serum amylase and lipase levels significantly increased in rats with cerulein-induced pancreatitis despite the presence or absence of LPS, but recovery of these pancreatic dysfunctions was slower in the group given LPS. However, serum GOT, GPT, BUN and creatinine levels were significantly elevated only in MOF rats. In the MOF rats, the MPO level in the lung was significantly elevated and arterial oxygen pressure was decreased, indicating that infiltration of neutrophils into the lung might be involved in pulmonary dysfunction. However, the MPO levels in the pancreas and kidney in the MOF rats were not remarkably different from those in normal rats. The inhibitory effects of YM264 and compound 1 on mortality and organ dysfunction were examined in this MOF model. The 24-h survival rate for rats prophylactically and therapeutically treated with an intravenous infusion of YM264 at 0.1 mg/kg h was significantly higher than that of controls. The 24-h survival rate for rats treated prophylactically by intravenous infusion of 2 mg/kg h of compound 1 was significantly higher than that of control, whereas a beneficial dose of compound 1 was 5 mg/kg h in therapeutically treated rats. Prophylactic treatment with YM264 (0.1 mg/kg h) and compound 1 (2 mg/kg h) ameliorated organ dysfunction in rats with MOF. In conclusion, pancreatic, hepatic, renal and pulmonary dysfunctions are observed in this rat MOF model. The PAF receptor antagonist and neutrophil elastase inhibitor reduce the mortality rate in rats with MOF due to their inhibitory effects on organ dysfunction, indicating that PAF and neutrophil elastase may play important roles in the development of MOF. These results in the present model are largely consistent with those in patients with MOF, indicating that this model is suited for MOF in humans and may be used as a model to test new therapeutic approaches.
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PMID:Protective effects of a PAF receptor antagonist and a neutrophil elastase inhibitor on multiple organ failure induced by cerulein plus lipopolysaccharide in rats. 975 12

We evaluated the ability of intravenous supplementation therapy with alpha(1)-antitrypsin (AAT) to reduce the rate of urinary excretion of desmosine (DES), a specific marker of elastin degradation, in eight men and four women with emphysema due to severe, congenital deficiency of AAT (range 17-69 mg/dl). Nine were former cigarette smokers, two were current smokers, and one reported never smoking; their mean age was 54 (SD 12) yr and their mean FEV(1) was 41 (18%) of predicted. Urinary DES was measured by isotope dilution and HPLC. Prior to the start of AAT supplementation, mean DES excretion was 13.0 (5.0) microg/g creatinine, 73% higher than in healthy nonsmokers. During 8 wk of supplementation therapy, mean urinary DES excretion was 13.0 (5.9) microg/g creatinine, unchanged from the baseline period (p = 0.85 by repeated measures ANOVA). We conclude that baseline levels of elastin degradation in emphysematous patients with severe AAT deficiency were abnormally high and that 8 wk of AAT supplementation therapy did not appreciably reduce the rate of elastin degradation. These findings raise the possibilities that protective levels of AAT in the lungs are insufficient or that elastin degradation in the lungs of these subjects is not dependent upon neutrophil elastase at this time.
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PMID:Short-term supplementation therapy does not affect elastin degradation in severe alpha(1)-antitrypsin deficiency. The American-Italian AATD Study Group. 1111 16

Bikunin (BK) is a Kunitz-type proteinase inhibitor responsible for most of the antitryptic activity of urine and so is known as the urinary trypsin inhibitor. As its excretion increases in inflammatory conditions, it is often considered to be a positive acute phase protein (APP). However, the gene for BK is downregulated in inflammation. In human plasma the major part of BK is covalently linked through a glycosaminoglycan chain to one or two homologous peptide heavy chains, thus forming high molecular weight proteinase inhibitors called pre-alpha-inhibitor (PalphaI) and inter-alpha-inhibitor (IalphaI), respectively. The C-terminal parts of these heavy chains are very sensitive to proteolysis. Neutrophil proteinases in particular are able to release from IalphaI and PalphaI BK (M, about 25,000) which retains its antitryptic activity and is quickly excreted in urine. It was therefore an early supposition that the higher urinary excretion of BK occurring during inflammatory diseases should be, at least in some respect, related to a partial proteolysis of IalphaI and PalphaI. In this study we observed that BK, determined as antitryptic activity, was clearly increased in urine from 35 patients with inflammatory diseases varying in origin and severity (76.5 +/- 75.5 IU/g vs. reference value <10 IU/g creatinine). This increase seems mainly to be associated with polymorphonuclear leukocyte activation, monitored by human leukocyte elastase (HLE) determination rather than with the acute phase response assessed by C-reactive protein (CRP) measurement. For all the patients we found that the urinary levels of BK and serum concentration of intact IalphaI correlated inversely (r=-0.36; p=0.03), in agreement with the presumed precursor-product relationship linking IalphaI and BK. We also proved that urinary BK was significantly higher, and serum IalphaI was significantly lower, in samples with plasma HLE values above the reference: 90 microg/l. Taken together, our results demonstrate that BK, the urinary excretion of which is increased in inflammatory conditions, originates, at least partly, from IalphaI and PalphaI by proteolytic cleavage. Consequently, urinary BK determination provides information on the severity of systemic proteolysis occurring in inflammation. We also demonstrated that during inflammatory diseases IalphaI and PalphaI concentrations in serum are dependent on their increased utilization as well as on the regulation of their biosynthesis.
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PMID:Urinary bikunin determination provides insight into proteinase/proteinase inhibitor imbalance in patients with inflammatory diseases. 1221 52


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