Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The protease inhibitor aprotinin was given a) in experimental septic shock, and b) in patients with hepatic cirrhosis and ascites, since in both conditions, activation of the plasma kallikrein-kinin system is associated with pathological systemic vasodilatation, which may trigger reflex neuroendocrine activation and renal solute retention. Given early in experimental sepsis, aprotinin maintained the arterial pressure, systemic vascular resistance (SVR), creatinine clearance and sodium excretion, all of which fell in controls. Aprotinin also blocked increases in pulmonary artery pressure and plasma renin activity (PRA). Given late in sepsis, aprotinin caused a rapid rise in arterial pressure and SVR towards baseline levels. In cirrhosis, aprotinin increased SVR in patients with low baseline values, and improved glomerular filtration rate, renal plasma flow and sodium excretion in all subjects; PRA was suppressed by aprotinin. Aprotinin reverses pathological systemic vasodilatation in these two conditions, and this is associated with a reduction in renin release and improved renal function.
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PMID:Vasoactive effects of aprotinin. 128 72

To better understand the role of granulocyte elastase (GE) in mediating tissue injury during sepsis, GE levels were measured in plasma and bronchoalveolar lavage fluid (BALF) in patients with septic shock (n = 16) and hemorrhagic shock (n = 30). Granulocyte elastase levels were compared to levels of alpha 1-protease inhibitor (alpha 1-PI). Results show that although plasma GE-alpha 1-PI complex was initially elevated in patients with hemorrhagic and septic shock, elevations in plasma GE-alpha 1-PI complex (831 +/- 241 micrograms/L) persisted in septic shock patients. alpha 1-Protease inhibitor levels in serum were increased, resulting in an inhibition of serum GE activity. Granulocyte elastase activity in BALF, however, was significantly higher in those patients with septic, as compared to hemorrhagic shock (31.4 +/- 25.8 versus 3.7 +/- 4.0 U/L, respectively). In addition GE levels were compared to other parameters, including respiratory index, blood neutrophil count, and plasma levels of endotoxin, fibronectin, and coagulation factor XIII. Significant correlations were observed between GE-alpha 1-PI and increased endotoxin concentration and decreased fibronectin and coagulation factor XIII levels. Significant correlation was found also between GE activity in BALF and respiratory index. These findings suggest that severe tissue damage occurred in patients with septic shock complicated by multiple-organ failure. Although GE activity appeared to be adequately inhibited by alpha 1-PI in blood, increased GE activity in local tissues, such as lung alveoli, may be responsible for significant local tissue injury during septic shock.
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PMID:Role of granulocyte elastase in tissue injury in patients with septic shock complicated by multiple-organ failure. 198 43

Muscle catabolism during sepsis is mainly caused by myofibrillar protein breakdown. The mechanism of this metabolic response is not known. We tested the hypothesis that increased protein breakdown in the extensor digitorum longus (EDL) muscle of septic rats is caused by increased activity of the so-called myofibrillar proteinase, which is a nonlysosomal proteolytic enzyme, and cathepsin B, which is a lysosomal proteinase. Sepsis, induced in male Sprague-Dawley rats (50 to 60 g) by cecal ligation and puncture (CLP), resulted in an approximately 50% increase in myofibrillar proteinase activity and an approximately 30% increase in cathepsin B activity. Concomitantly, both total and myofibrillar protein breakdown rates, measured as release of tyrosine and 3-methylhistidine (3-MH), respectively, by incubated EDL muscles, were substantially elevated. Treatment of septic rats with the mast cell degranulating compound 48/80 or the lysosomal protease inhibitor leupeptin significantly reduced myofibrillar proteinase and cathepsin B activities, but did not affect protein breakdown rates. The results suggest that increased protein breakdown in septic skeletal muscle is associated with, but not caused by, myofibrillar proteinase or cathepsin B activity. The data also support the concept of a mast cell origin of the myofibrillar proteinase activity, but do not suggest an obligatory involvement of mast cell proteinase in increased protein degradation during sepsis.
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PMID:Myofibrillar proteinase, cathepsin B, and protein breakdown rates in skeletal muscle from septic rats. 200 44

Basic therapeutic methods based on early diagnosis of septic ARDS were described. Concerning early diagnosis exertional hypoxemia and increased broncho-vascular markings on chest X-ray were observed in the pre-ARDS stage of septic patients. These findings were also observed in the initial stage of endotoxin-induced pulmonary edema in rabbits and the basic mechanisms were thought to be as follows, based or our experimental studies. The former is related on impairment of alveolar diffusion and the latter reflect increased peri-vascular cuffing due to increase in pulmonary edema. The diffuse infiltrative shadows on the both back area in CT scanning was also a helpful sign indicating the early stage of pulmonary edema. This finding was seen at the stage at which the edematous shadow had not yet appeared on conventional chest X-ray. Increase in serum laminin and decrease in plasma fibronectin were also important biochemical findings predicting ARDS in gram negative sepsis. Using these findings, it is considered that early prediction of septic ARDS is possible. Concerning therapeutic methods based on early prediction, the usefulness of cortico-steroids and the protease inhibitor "Urinastatin" were observed in experimental in vitro and in vivo studies. Some findings induced by endotoxin administration in rats or rabbits, such as the increase in endotoxin in peripheral blood, the distraction of PMN-elastase, the increase in pulmonary lymph flow and mortality within 48 hours were significantly suppressed by simultaneous treatment by corticosteroid. In an in vitro study, PMN superoxide production and elastase release following incubation of endotoxin and PMNs were significantly inhibited by adding a concomitant level of corticosteroid and/or urinastatin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Sepsis and ARDS]. 203 89

Leukocyte elastase (LE) plays a role in the development of shock. Therefore, we examined the effects of urinastatin, a protease inhibitor, on LE in 7 patients with sepsis. LE levels before the administration of urinastatin were high in all patients, especially those in shock. Administration of urinastatin markedly decreased LE levels, with the decrease being more remarkable in patients showing high LE levels before treatment. These results suggest that urinastatin not only reduces LE levels but also suppresses factors that are involved in the development of septic shock.
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PMID:[Reduction in leukocyte elastase levels in patients with sepsis by administration of urinastatin]. 234 98

The level and functional activity of the major protease inhibitors in plasma and faecal extracts were analysed in 26 consecutive patients admitted during their first attack of acute severe colitis. The patients were retrospectively divided into two groups: one with total colitis and another with distal colitis. The patients with total colitis had a significantly lower alpha 2-macroglobulin level in plasma than normal individuals and patients with distal disease, whereas no difference in the levels of alpha 1-protease inhibitor, antichymotrypsin, antithrombin III, and alpha 2-antiplasmin was noted between the two groups. The protease-inhibiting capacity was saturated, and free proteolytic activity was present in the faecal extracts. In the extracts complex formation was demonstrated between leukocyte proteases and the antiproteases alpha 1-protease inhibitor and alpha 2-macroglobulin. It is concluded that the low plasma level of alpha 2-macroglobulin in patients with severe total colitis is mainly due to a consumption caused by complex formation with proteases, as earlier demonstrated in patients with acute pancreatitis and sepsis.
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PMID:Protease inhibitors in plasma and faecal extracts from patients with active inflammatory bowel disease. 242 96

To test the hypothesis that the broad spectrum protease inhibitor, aprotinin, can prevent early pathophysiology of sepsis, we administered endotoxin (0.1-0.75 microgram/kg) by a 30-min infusion to awake goats. Animals were used as their own controls receiving endotoxin with no treatment on one day and treatment with a bolus injection (10 trypsin inhibitory units, TIU, per kg) followed by a 6-hr infusion (5 TIU/kg/hr) of aprotinin on another. The effect on systemic and pulmonary hemodynamics, lung lung lymph flow (QL), lymph plasma protein ratio (L/P), and systemic eicosanoid levels were assessed. QL quickly reached 28 ml/hr (four times baseline) in both groups then slowly returned toward baseline. L/P ratio of both groups decreased by about 10% then returned to baseline. QL and L/P were not different between groups. Likewise, vascular parameters were not different between groups. Mean pulmonary artery pressure increased approximately 150% to a peak of 58 cm H2O in both groups while pulmonary artery wedge pressure doubled from a baseline of 8 cm H2O then both groups returned to baseline. Systemic arterial pressure decreased over the 6 hr experimental period by 15 Torr to 70 Torr in both groups. Cardiac output declined from 4.3 to 3 liter/min after the endotoxin, remaining at the level for 2 hr then progressively increased to about 5 liter/min in both groups. We conclude that aprotinin, in doses similar to those reported to give protection from acute lung injury of various origins, fails to modify the early cardiopulmonary pathophysiology of endotoxin.
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PMID:Lung permeability and hemodynamics during endotoxemia: effect of aprotinin. 243 Dec 22

Impaired fibrinolysis may contribute to development of adult respiratory distress syndrome (ARDS). Pathologic increases in endogenous plasminogen activator inhibitor (PAI-1) may blunt normal fibrinolysis and unmask alternate fibrinolytic mechanisms, such as elastase-induced fibrin degradation. We measured PAI-1 and elastase-induced fibrin(ogen) degradation products in 69 critically ill patients in our medical intensive care unit (MICU) and in nine healthy volunteers. Factor VIII-related antigen protein (VIII:Ag), a reported marker of acute lung injury, and alpha-1-protease inhibitor (alpha-1-PI), an acute phase reactant, were also measured. MICU patients included 24 control patients with no known risk of ARDS, 35 patients with risk factors for ARDS including sepsis, pneumonia, aspiration, and shock, and 12 patients with ARDS including two patients from at-risk groups who developed ARDS. Plasma PAI-1 was determined by chromogenic assay, elastase-induced peptides by a new radioimmunoassay, VIII:Ag by immunoelectrophoresis, and alpha-1-PI by immunodiffusion. When compared to normal volunteers, MICU control patients had elevated PAI-1, VIII:Ag, elastase-induced peptides, and alpha-1-PI. Patients with ARDS had significantly higher PAI-1 and VIII:Ag than did MICU control patients; elastase-induced peptides and alpha-1-PI were not higher. However, at-risk patients who did not develop ARDS also had high PAI-1 or VIII:Ag. Although these data cannot refute the possible role of these compounds in the pathogenesis of ARDS, they demonstrate that PAI-1 and VIII:Ag may be elevated in many critically ill patients but may not be useful markers for the subsequent development of ARDS.
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PMID:Fibrinolysis in critically ill patients. 250 87

A 33-year-old woman was admitted as an emergency case because of shock condition after delivery. Physical examination revealed fever, cyanosis and coarse crackles throughout the entire chest. Laboratory data showed leukocytosis and increase of CRP value. Adult respiratory distress syndrome (ARDS) was diagnosed based on progressive severe hypoxemia and bilateral diffuse alveolar shadows on chest X-ray film. The cause of ARDS was considered to be septicemia as staphylococcus aureus was cultured from lochia. The patient was intubated, then artificially ventilated employing PEEP. Chemotherapy using three different kinds of antibiotics was started, combined with the administration of corticosteroid and a protease inhibitor, Urinastatin. The patient finally recovered completely.
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PMID:[A cured case of adult respiratory distress syndrome caused by septicemia of Staphylococcus aureus]. 269 22

We compared retrospectively four similar groups of patients with multiple organ failure (MOF) due to sepsis. All of them were treated initially with conventional therapy, aprotinin as protease inhibitor and vitamin C with allopurinol as possible scavengers of oxygen-free radicals, were also added. After 24 h of no clinical progress, continuous arteriovenous hemofiltration (CAVH), CAVH/dialysis (CAVH/D), and sequential plasmafilter-dialysis with slow continuous hemofiltration (CAVHP/D) were respectively added to groups 2 (n = 14), 3 (n = 6), and 4 (n = 11). Mortality was 87% for group 1, 71% for group 2, 50% for group 3, and 36% for group 4. In the latter we were able to remove possible MOF-inducing mediators from the bloodstream, to give fluids without restriction (even in oliguric patients), and to improve removal of metabolic waste products. It is possible that these extracorporeal supports, associated with conventional therapy, and pharmacologic drugs such as protease inhibitors and possible scavengers of oxygen-free radicals, helped to reduce the mortality rate. We conclude that, although the number of study patients was too small to reach firm conclusions, the good results observed with CAVHP/D suggest clinical trials to assess the efficacy of this technique.
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PMID:Use of extracorporeal supportive techniques as additional treatment for septic-induced multiple organ failure patients. 273 23


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