Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have demonstrated that plasma tissue plasminogen activator (t-PA) level was elevated in patients with liver disease. In this study, t-PA antigen levels were investigated in patients with acute hepatitis (AH; N = 12), chronic hepatitis (CH; N = 8), compensated liver cirrhosis (CLC; N = 40), decompensated liver cirrhosis (DLC; N = 23) and hepatocellular carcinoma (HCC; N = 35). The increased t-PA levels (higher than 14 ng/ml) were found in 33% (4/12) of AH on the early hospital days, 25% (2/8) of CH, 45% (18/40) of CLC and 91% (21/23) of DLC, and 60% (21/35) of Hcc cases. In patient with LC, the correlations between t-PA levels and serum total bilirubin (T.Bill) and hepatic synthetic functions were investigated. The results were that the t-PA levels correlated positively with T. Bil and negatively with liver synthetic functions such as albumin, protein C and choline-esterase, indicating that t-PA increased almost in proportion to the deterioration of hepatic function. Serial determination of t-PA in patients with HCC treated by transcatheter arterial embolization (TAE) revealed that TAE failed to normalize the t-PA levels. In one case of HCC complicated with disseminated intravascular coagulation (DIC), t-PA showed a marked increase at acute phase of DIC and subsequent decrease after the successful treatment for DIC by gabexate mesilate (FOY) infusion. These results suggest that increased t-PA in liver disease is due mainly to deterioration of hepatic function, and that secondary fibrinolytic state, such as DIC, is also a contributing factor.
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PMID:[Evaluation of plasma tissue plasminogen activator (I-PA) levels in patients with liver diseases]. 210 6

Patients with liver disease frequently have multiple hemostatic abnormalities. Coagulation and fibrinolytic factors and inhibitors may decrease as the result of impaired synthesis and/or enhanced catabolism. In order to assess the actual degree of activation of coagulation and fibrinolytic systems in liver disease, plasma levels of thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-antiplasmin complex (PAP) were measured together with cross-linked fibrin derivatives (XDP), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI-1) in 31 patients with liver disease (five patients with acute hepatitis, seven with chronic hepatitis, nine with liver cirrhosis, and ten with hepatocellular carcinoma). Mean plasma levels of TAT (mean 4.2 +/- SD 4.0 micrograms/L), PAP (0.7 +/- 0.7 mg/L), and XDP (374 +/- 518 micrograms/L) were significantly elevated in patients with liver disease as compared with normal subjects (TAT of 1.7 +/- 0.3 micrograms/L, PAP of 0.2 +/- 0.1 mg/L, and XDP of 30 +/- 14 micrograms/L; P less than 0.005). Plasma concentrations of t-PA and PAI-1 antigens were also elevated. When plotted by the disease categories, the magnitude of elevations of these parameters was variable among subgroups. Patients with acute hepatitis had considerably higher TAT levels. The mean PAP values were relatively high in chronic hepatitis and hepatocellular carcinoma, in which an elevation of the t-PA/PAI-1 ratio was observed. Although clearance of TAT and PAP should be evaluated in the future, these findings suggest that excessive amounts of thrombin and plasmin are actually generated in patients with liver disease.
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PMID:Thrombin and plasmin generation in patients with liver disease. 252 2

Activated macrophages (m phi) exhibited cytotoxic effects on isolated liver cells and produced plasminogen activator (PA) in vitro. A high molecular weight fraction of normal human serum (Fr-1) was shown to reduce the m phi-mediated hepatocytotoxicity and enhance the PA activity of activated m phi. Conversely, a lower molecular weight fraction of serum (Fr-3) was found to enhance the hepatotoxic potential and decrease the PA activity of activated m phi. Although similar effects were seen with serum fraction prepared from patients with acute hepatitis, somewhat different influences were observed with serum components from patients with chronic active hepatitis or liver cirrhosis: Fr-1 from patients with chronic active hepatitis was less active in reducing m phi-mediated hepatocytotoxicity, and and Fr-3 was more active in enhancing it, in comparison with fractions from individuals or patients with active hepatitis. Fr-3 from patients with liver cirrhosis was shown to be remarkably less active in enhancing m phi-mediated hepatocytotoxicity. Furthermore, Fr-1 from patients with liver cirrhosis reduced PA activity, Fr-3 was less active in decreasing such activity. These findings suggest that the serum components may regulate m phi-mediated hepatocytotoxicity as well as PA secretion of activated m phi. Our studies also suggested the possibility that relative doses of these serum components may differ in various pathological conditions of the liver.
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PMID:Modulation of the macrophage hepatocytotoxicity and plasminogen activator activity of activated macrophages from guinea pigs by serum components from normal human and patients with liver diseases. 668 38

We studied the tissue plasminogen activator (t-PA) levels in the plasma of patients with acute hepatitis (AH), severe acute hepatitis (AHs) and fulminant hepatitis (FH). Plasma t-PA levels were measured consecutively on the first, third and seventh days of hospitalization. Plasma t-PA levels were markedly higher in AHs and FH than in AH (p < 0.05, p < 0.01, respectively) on the first day, but did not differ significantly between AHs and FH on this day. The t-PA levels decreased markedly on the third and seventh days in AHs (both p < 0.05), but did not change from the first day to the third and seventh days in FH. The t-PA levels on the third and seventh days were higher in FH than in AHs (both p < 0.05). There was a significant increase in the plasma t-PA level before an episode of encephalopathy in FH compared with levels in AHs. These observations suggest that t-PA level may be useful as a prognostic parameter in patients with acute hepatic injury.
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PMID:[The clinical significance of plasma tissue plasminogen activator (t-PA) levels in severe acute or fulminant hepatitis]. 955 77

Strict regulation of the distribution and degradation kinetics is the ultimate aim of drug delivery system. Regulation of drug delivery would increase the therapeutic efficacy and decrease the potential side effects. We encapsulated and used Z-Asp, a caspase inhibitor in poly-N-p-vinylbenzyl-D-lactonamide (PVLA) coated-poly (L-lactic acid) (PLA)-nanospheres in a mouse model of acute hepatitis. These nanospheres were internalized and accumulated in hepatocytes both in vitro and in vivo. Encapsulation significantly extended the intracellular retention time of the content in hepatocytes, which increased the bioavailability of the caspase inhibitor. In addition, the therapeutic effect was temporally controllable in vivo by modifying the component of the nanospheres. A cocktail of nanospheres with diverse degradation kinetics showed persistent therapeutic effects in acute hepatitis, and only nanospheres that targeted hepatocytes and controlled degradation rescued mice from lethal hepatic injury. This temporally and spatially controlled drug delivery system could be used in various liver diseases.
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PMID:Design of a temporally and spatially controlled drug delivery system for the treatment of liver diseases in mice. 1109 49