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)

Effects of retrograde injection into the pancreatic duct and intravenous infusion of pancreatic enzymes and bile salt on the pancreas and other vital organs such as the liver and the lung were investigated in rats. Intraductal injection (1 ml/kg) of alpha-chymotrypsin (50-100 mg/ml), trypsin (10-100 mg/ml), pancreatic elastase (10 mg/ml), lipase (100-300 mg/ml), pancreatic kallikrein (25 mg/ml) and sodium taurocholate (50 mg/ml) solutions significantly increased pancreatic water content. Alpha-chymotrypsin, pancreatic elastase, taurocholate and trypsin elicited gross pancreatic hemorrhage. In contrast, lipase and kallikrein elicited gross pancreatic edema, but not hemorrhage. Intravenous infusion of trypsin (1 mg/kg/hr) and pancreatic elastase (10 mg/kg/hr) significantly increased pulmonary vascular permeability in rats, whereas infusion of neutrophil elastase (0.3 mg/kg/hr) did not elicit these effects. Only trypsin slightly reduced arterial oxygen pressure. These results show pancreatic enzymes and bile salts induce pancreatic inflammation after retrograde injection into the pancreatic duct in rats. Furthermore, trypsin and pancreatic elastase extravasation into the vascular system can lead to pulmonary dysfunction in rats.
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PMID:Pancreatic enzyme-induced pancreatitis and systemic complications in rats. 971 65

The imbalance of neutrophil elastase and alpha1-antitrypsin in pleural effusion after lobectomy and the effects of the neutrophil elastase inhibitors, sodium N-[2-[4-(2,2-Dimethylpropionyloxy)phenyl-sulfonylamino]benzo yl]aminoacetic acid (ONO-5046) and purified alpha1-antitrypsin, on neutrophil elastase activity were determined. The amount of neutrophil elastase complexed to alpha1-antitrypsin, measured by an enzyme-linked immunosorbent assay, was 170 times higher in pleural effusion than in blood 3 h after lobectomy. The alpha1-antitrypsin levels measured by laser nephelometry did not increase in either blood or pleural effusion. Although neutrophil elastase activity, measured by the hydrolysis of succinyl-(Ala)3-p-nitroanilide, was not detected in blood, it was increased in pleural effusion 3 h and 24 h after lobectomy. ONO-5046, but not alpha1-antitrypsin, reduced the neutrophil elastase activity in pleural effusion. There is an imbalance of neutrophil elastase and alpha1-antitrypsin in pleural effusion after lobectomy. ONO-5046 is a potent inhibitor of neutrophil elastase activity in human pleural effusion.
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PMID:ONO-5046 is a potent inhibitor of neutrophil elastase in human pleural effusion after lobectomy. 972 57

Single-dose toxicity studies of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel neutrophil elastase inhibitor, were conducted in Sprague-Dawley (SD) rats and beagle dogs. The rats of both sexes were administered ONO-5046.Na intravenously at a single dose of 150, 300 or 450 mg/kg. The male dogs were also given ONO-5046.Na at a single dose of 75 or 150 mg/kg. In the rat study, hypoactivity, bradypnea and paleness of limbs and pinna were observed at doses of 300 mg/kg and above. In particular, one of six female rats in the 450 mg/kg group showed clonic convulsion and died. In surviving animals, those signs disappeared within 3 hr after administration. No effect on body weight gain was seen in either group. Necropsy findings showed a slight foamy fluid in the bronchus, hemorrhage at the right knee joint muscle, tendon and lung in a dead animal. In the dog study, no effects on clinical signs, body weight, food consumption and blood biochemistry were seen in any animals of the 75 and 150 mg/kg groups. It is concluded that the approximate lethal doses are 450 mg/kg in rats and 150 mg/kg and above in dogs.
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PMID:[Toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (1). Single-dose intravenous toxicity studies in rats and dogs]. 976 Apr 3

A 4-week repeated dose toxicity study with 4-week recovery test of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel neutrophil elastase inhibitor, was conducted in Sprague-Dawley (SD) rats. The rats of both sexes were administered ONO-5046.Na intravenously at a daily dose of 0 (vehicle control and saline control), 18.75, 37.5, 75 or 150 mg/kg. ONO-5046.Na did not affect signs, body weight, food consumption, ophthalmology, urinalysis, hematology, blood chemistry, organ weights, necropsy or histopathology at any dose. These results indicate that the NOAEL of (ONO-5046.Na in rats is 150 mg/kg/day for both sexes in this study.
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PMID:[Toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (2). 4-week repeated dose intravenous toxicity study in rats with 4-week recovery test]. 976 Apr 4

4-week repeated dose toxicity study with 4-week recovery test of sodium N-[2-[4-(2, 2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel neutrophil elastase inhibitor, was conducted in beagle dogs. The dogs of both sexes were administered ONO-5046.Na intravenously at a daily dose of 0 (vehicle control), 7.5, 15 or 30 mg/kg. In the 15 mg/kg female group and the 30 mg/kg male and female groups, transient hypoactivity and ataxic gait were observed. It is considered that these symptoms were attributed to the pharmacological effect of ONO-5046.Na. Also, in the 30 mg/kg male and female groups, erythrocyte, hematocrit and hemoglobin were decreased. In the 30 mg/kg male group, lung weight was increased. However, histopathological examination revealed there were no changes in any organs including the lungs. There were no treatment-related changes in body weights, food consumption, ophthalmology, occult blood in feces, urinalysis, blood chemistry, electrocardiography, blood pressure, temperature, pulse rate, hepatic and renal function or necropsy. These results indicate that the NOAEL of ONO-5046.Na in dogs in 15 mg/kg/day for both sexes in this study.
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PMID:[Toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (3). 4-week repeated dose intravenous toxicity study in dogs with 4-week recovery test]. 976 Apr 5

A 6-month repeated dose toxicity study with 1-month recovery test of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel neutrophil elastase inhibitor, was conducted in Sprague-Dawley (SD) rats. The rats of both sexes were administered ONO-5046.Na intravenously at a daily dose of 0 (vehicle control), 18.75, 37.5 or 75 mg/kg. ONO-5046.Na did not affect clinical signs, body weight, food consumption, opthalmology, urinalysis, hematology, blood chemistry, organ weight, necropsy or histopathology at any dose. These results indicate that the NOAEL of ONO-5046.Na in rats is 75 mg/kg/day for both sexes in this study.
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PMID:[Toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (4). 6-month repeated dose intravenous toxicity study in rats with 1-month recovery test]. 976 Apr 6

A 6-month repeated dose toxicity study with 1-month recovery test of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel neutrophil elastase inhibitor, was conducted in beagle dogs. The dogs of both sexes were administered ONO-5046.Na intravenously at a daily dose of 0 (vehicle control), 7.5, 15 or 30 mg/kg. In the 15 mg/kg and above groups, transient ataxic gait was observed. It is considered that this symptom could be attributed to the pharmacological effect of ONO-5046.Na. Macro- and microscopic hemorrhage at the injection site was observed in the ONO-5046.Na treated groups. However, it is considered that these findings could be attributed to the long-term repeated dosing procedure, and were not toxic changes. There were no treatment-related changes in body weight, food consumption, ophthalmology, urinalysis, hematology, blood chemistry, electrocardiography and organ weights. These results indicate that the NOAEL of ONO-5046.Na in dogs is 30 mg/kg/day for both sexes in this study.
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PMID:[Toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (5). 6-month repeated dose intravenous toxicity study in dogs with 1-month recovery test]. 976 Apr 7

Fertility study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel neutrophil elastase inhibitor, was conducted in Sprague-Dawley (SD) rats. ONO-5046.Na was administered intravenously at doses of 18.75, 37.5 and 75 mg/kg/day to male rats from 64 prior to mating, through the mating period and until necropsy, and to female rats from 15 days prior to mating until Day 7 of gestation, in order to examine its effects on fertility and reproductive performance of males and females and the development of their fetuses. There were no changes attributable to ONO-5046.Na in general signs, body weight, food consumption or autopsy findings in males and females. No drug-related changes were observed in estrous cycles, copulation and fertility indices in males and females. Pituitary weight of dams was decreased in each of the ONO-5046.Na treated groups, but no histopathological changes were observed in the pituitary. In the cesarean section findings in dams, ONO-5046.Na had no effects on the number of corpola lutea, the number of live fetuses, the implantation ratio, the resorbed and dead fetus ratio, fetal or placental weight, or the incidences of external, skeletal or visceral anomalies of the fetuses. From these results, it is considered that the NOAEL of ONO-5046.Na is 75 mg/kg/day for general and reproductive toxicity in males and females and for developmental toxicity in their fetuses.
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PMID:[Reproductive and developmental toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na (1). Fertility study in rats]. 976 Apr 8

Prenatal and postnatal toxicity of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel inhibitor of human neutrophil elastase, was studied in Sprague-Dawley (SD) rats. ONO-5046.Na was injected intravenously at doses of 0, 18.75, 37.5 and 75 mg/kg/day to pregnant rats from day 7 of pregnancy to day 20 after delivery. All pregnant rats were allowed to deliver naturally for postnatal examination of their offspring. No adverse effects on dams were observed in clinical signs, body weight change, food consumption, pregnant, delivery or lactating performances. ONO-5046.Na did not affect the postnatal development of offspring, including birth index, survival index, physical and functional development, motor activity, emotionality, learning ability and reproductive performance. From these results, it is considered that the NOAEL of ONO-5046.Na is 75 mg/kg/day for dams and their offspring.
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PMID:[Reproductive and developmental toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (2). Study for effects on pre- and postnatal development in rats, including maternal function]. 976 Apr 9

Teratogenicity of sodium N[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino]benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel inhibitor of human neutrophil elastase, was studied. ONO-5046.Na was injected intravenously at doses of 0, 7.5, 15 and 30 mg/kg/day to pregnant Kbl: NZW rabbits from day 6 to day 18 of pregnancy. All female rabbits were sacrificed on day 29 of pregnancy and their fetuses were examined. There were no clinical signs or death attributable to ONO-5046.Na. One dam in the control group and 3 dams in the 30 mg/kg/day group aborted. Body weight gain in the 15 and 20 mg/kg/day groups and food intake in the 30 mg/kg/day group were decreased during the administration period. These changes had recovered by the end of the study. Kidney weight was increased in the 30 mg/kg/day group. There were no effects of ONO-5046.Na in necropsy findings at cesarean section in dams at any dose levels. Developmental toxicity of ONO-5046.Na was not found at any dose levels. From these results, it is considered that the NOAEL of ONO-5046.Na is 7.5 mg/kg/day for pregnant animals and 30 mg/kg/day for fetuses.
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PMID:[Reproductive and developmental toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (3). Teratogenicity study in rabbits]. 976 Apr 10


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