Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aprotinin, a protease inhibitor, has been used in a wide variety of pathophysiological states thought to be associated with an increase in protease activity. Opinion differ with respect to the success of the therapy. This paper proposes a rationale for the therapeutic action of aprotinin based on biochemical and physiological evidence. In the kallikrein-kinin system, in addition to kallikrein, other serine-esterases such as trypsin, plasmin, etc. can generate kinin production. In certain disease states such as pancreatitis there is not only an increase in serine-protease activity but frequently these enzymes reach parts of the organism where they are not found in health. Thus in such circumstances increased production of kinins can result. The consequences of increased kinin generation are discussed in light of work indicating their role in metabolic and circulatory homeostasis. Aprotinin is specifically a serine-esterase inhibitor. It is suggested that perhaps the most important action of this compound is as an inhibitor of the kallikrein-kinin system. On this basis a therapeutic regime in various disease states for the use of aprotinin, which allows for control of kinin generation, is suggested.
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PMID:A rationale for the therapeutic action of aprotinin. 15 36

253 patients with acute pancreatitis were treated in clinic for surgery in Zagreb through last 23 years. The most frequent cause of pancreatitis were diseases of biliary tract, obesity, vascular deseases, alcoholism etc. In the symtomatology, the pain was present in all patients and majority of them had abdominal symptoms as well. Most of the patients came to the treatment within the firsts 24 to 48 hours. Besides Trasylol various conservative therapy was applied and some patients were operated either on billiary ducts or on pancreas. 85 patients had to be operated again on billiary tract afterwards. From 253 patients treated 24 died (9,48%) because of the necrosis of pancreas and alterations on various other organs.
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PMID:[253 patients with acute pancreatitis treated at the surgical clinic in Zagreb]. 30 Sep 70

Acute pancreatitis may present as the mild edematous type or the more rare and dangerous hemorrhagic form. The effects of the latter are believed to be due to the activation of pancreatic enzymes, notably trypsin. Therefore attempts are being directed towards suppression of pancreatic enzyme activation in the management of the condition. Aprotinin and glucagon are the agents for this purpose that have received most attention. Patients with acute hemorrhagic pancreatitis are subject to respiratory failure, which is not detectable early by clinical evidence, so that early monitoring of pulmonary function by the determination of arterial blood-gas pressures is desirable. This is borne out by the findings in six fatal cases.
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PMID:Symposium on pancreatitis: 1. Conservative management of acute pancreatitis. 30 73

The plasma esterolytic activity was measured using benzyol arginine ethyl ester (BAEe) in the peripheral venous blood of patients with acute pancreatitis, normal healthy volunteers and a contrast group of patients with acute intrabdominal inflammations other than acute pancreatitis. The plasma esterolytic activity was significantly elevated in the pancreatitis group. This activity was maximal during the first 48 hours of the illness and remained elevated for a further 8 days thereafter. Aprotinin in a dose of 2000 K.I. u/0-3 ml plasma did not completely inhibit this esterolytic activity, although it resulted in a more substantial inhibition than either ovomucoid or soy bean inhibitor. It is concluded that pancreatic enzymes are released into the circulation during acute pancreatitis and that Aprotinin does not completely inhibit this proteolytic activity. This polyvalent proteinase inhibitor should therefore be administered in much higher dosage than that used hitherto in acute pancreatitis. The plasma esterolytic activity seems to be of diagnostic value in acute pancreatitis.
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PMID:Estimation of plasma esterolytic activity and its in vitro inhibition by proteinase inhibitors during acute pancreatitis in the human. 108 38

In canine pancreatitis, irreversible hypotension and death follow saturation of the antiprotease molecules in peritoneal exudate by activated proteolytic enzymes which are released from the pancreas. This study has examined, in rats with taurocholate-induced pancreatitis, the efficacy of removal of the peritoneal exudate by aspiration and a single lavage, followed by instillation of an exogenous antiprotease solution. Instillation of human fresh frozen plasma, containing alpha 2-macroglobulin and alpha 1-antiprotease, was associated with the longest median survival. Aprotinin, although possessing a much greater trypsin inhibitory capacity, just failed to significantly improve the median survival time compared with the control group. Intraperitoneal antiprotease therapy is simple to perform, has a beneficial effect on survival time in this model and merits investigation in man.
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PMID:Effective intraperitoneal antiprotease therapy for taurocholate-induced pancreatitis in rats. 203 16

Dog polymorphonuclear leukocyte cathepsin G was isolated from a granule extract using a two-step procedure including affinity chromatography on a Trasylol-Sepharose gel and ion-exchange chromatography on a CM 52 column. 22 of the first 24 N-terminal amino acids were determined and showed 83% and 71% identity to those of human and rat cathepsin G, respectively. Total amino-acid composition demonstrated the basic nature of the protein. In an SDS/polyacrylamide-gel electrophoresis the protein showed an Mr of 29,400 compared to the Mr of 26,800 calculated from the total amino-acid composition. The enzyme was shown to form complexes with alpha 1 alpha 2-macroglobulin and alpha 1-proteinase inhibitor. A specific enzyme-linked immunosorbent assay was developed for the determination of cathepsin G/alpha 1-proteinase inhibitor complex in dog plasma and tissue fluids. The mean concentration of cathepsin G in normal dog plasma was determined to be 38 micrograms/l, measured as cathepsin G/alpha 1-proteinase inhibitor complex. When active dog cathepsin G was added to normal dog plasma in vitro, approximately 56% could be measured by the assay. Slow intravenous infusion of a lethal dose of endotoxin in dogs was followed by a marked drop in white blood cell count and thrombocytes and a simultaneous rapid increase in plasma cathepsin G concentration, reaching a maximum level of 150 micrograms/l. Bile-induced experimental pancreatitis in dogs was accompanied by successive increase in cathepsin G levels in plasma as well as in peritoneal exudates, reaching a maximum level of about 300 micrograms/l in plasma and 18 mg/l in the exudates during the late stages of disease.
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PMID:Release of dog polymorphonuclear leukocyte cathepsin G, normally and in endotoxin and pancreatitic shock. Isolation and partial characterization of dog polymorphonuclear leukocyte cathepsin G. 191 May 80

We have analyzed the effects of aprotinin and Na2CaEDTA on phospholipase A2 activity and on the outcome of experimental pancreatitis in pigs. Hemorrhagic pancreatitis was induced in 29 piglets by infusing Na-taurocholate and trypsin into the pancreatic duct with simultaneous intravenous injection of secretin. Twelve animals serving as controls had no specific treatment. Nine animals were treated with aprotinin and eight pigs with Na2CaEDTA. Ten of the control animals died within 24 h of the induction of pancreatitis, and two of them lived for a week. In the aprotinin group three piglets died within 24 h and two died during the next day; four animals lived for a week. In the Na2CaEDTA group five animals died within 24 h and one the next day; two animals lived for a week. In all the animals serum phospholipase A2 activity increased significantly (p less than 0.01), there being no differences between the groups. In those animals that lived for a week the phospholipase A2 activities decreased on the 2nd day. This decrease was seen in both treated groups. Aprotinin prolonged the survival time of the animals. This prolongation was statistically significant (p less than 0.05, chi-square test, logrank test). Na2CaEDTA did not improve the prognosis of the animals. Neither of the drugs given influenced the serum phospholipase A2 activities during the first hours of the disease.
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PMID:Aprotinin and Na2CaEDTA in experimental hemorrhagic pancreatitis in pigs. 243 80

A group of 159 dogs divided in 8 sub-groups were studied, in regard to pancreatitis, the purpose of the study was to investigate the participation of the automatic nervous system in the course of acute pancreatitis. The procedures and the results were as follows: 1. Pancreatitis was induced in two forms: a) Injection of gallbladder bile, from the same animal to the pancreatic duct. b) Blind duodenal loop with exclusion of the distal duodenum through the pylorus. In both cases acute pancreatitis was obtained. Fat necrosis was predominant in type a, and hemorrhagic lesions in type b. 2. The anesthetic block of the celiac plexus controlled the pain and shock. The animals were in good general conditions but there were no changes in the pathological process of the pancreas. The same results were noted in surgical resections of splanchnic trunks. 3. When the surgical resections of splanchnic nerves was followed by a waiting period of 20 days from the production of pancreatitis there were no changes in the gland. 5. Vagotomy previous to pancreatitis does not have protector effects in the induction of pancreatitis. 6. Continuous perfusion of E.V. novocaine was of extreme utility. The animals remained without pain and the process remained stable when it was given in the initial face of edema. 7. The enzyme inhibitor (Trasylol) given in the first 24 hs. does not prove to be valuable. Due to the fermentative derangement the condition of the animals was better maintained in relation to the comparative animals.
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PMID:[Acute pancreatitis. Neurovascular and microcirculatory changes. Pathogenic and therapeutic study]. 246 25

In an experimental and clinical study a significant reduction of the postoperative edema after extracorporeal extremity perfusion under addition of Aprotinin was observed. Together with reduction of edema usually expected complications like pain and peripheral nerve damage could be reduced significantly. Preliminary, yet unpublished data on cytostatic infusion of the pancreas also indicate that intraarterial Aprotinin when given simultaneously may prevent pancreatitis. It is mandatory Aprotinin to be given early enough in sufficiently high dose and there seems to be an advantage when the arterial route is used.
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PMID:Inhibition of proteases during extracorporeal extremity perfusion experimental and clinical results. 246 10

A dog model was established to measure the hemodynamic changes occurring during experimental pancreatitis. The effect of treatment with Trasylol and vasopressin, beginning 60 minutes after induction of pancreatitis was assessed by their effect on the pancreatic hemodynamics. The pancreatic arterial blood flow fell by 72 per cent in the dogs with induced pancreatitis and treated only with saline solution. In contrast, the pancreatic blood flow fell by 58 per cent in the Trasylol group and 80 per cent in the vasopressin group. In addition, vasopressin had a detrimental effect on the cardiac output. Neither treatment altered the changes noted in the systemic blood pressure. Trasylol had a slight beneficial effect on experimental pancreatitis when assessed by its effect on the pancreatic hemodynamics. In contrast, vasopressin had a detrimental effect on the pancreatic hemodynamics.
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PMID:The effect of Trasylol and vasopressin on experimental pancreatitis. 615 20


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