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

In order to clarify the effect of hemodialysis (HD) on the fibrinolytic system, fibrinolytic activity was evaluated in 27 patients undergoing regular hemodialysis treatment (RDT) using new parameters including plasma alpha 2-plasmin inhibitor (alpha 2 PI), alpha 2-plasmin inhibitor-plasmin complex (alpha 2 PIC), cross-linked fibrin degradation products (XL-FDP), tissue plasminogen activator (t-PA) activity, t-PA antigen and plasminogen activator inhibitor-1 (PAI-1) antigen. Predialysis baseline levels of plasminogen and alpha 2PI activity in RDT patients were significantly lower and those of alpha 2PIC were significantly higher than normal control values. During a single HD session, alpha 2PIC exhibited a continuous, significant increase reaching about 180% of initial values by the end of HD. alpha 2PI activity was significantly decreased at the end of the HD, though there were no significant changes in plasminogen activity during HD. Predialysis baseline levels of XL-FDP in RDT patients were significantly higher than normal control values. No significant changes in XL-FDP were observed during HD. Both t-PA activity and t-PA antigen significantly increased during HD, and PAI-1 antigen significantly decreased during HD. Von Willebrand factor (vWF) antigen in plasma, which is regarded as reflecting a release reaction by vascular endothelial cells to certain stimuli, also significantly increased during HD. However, neither vWF antigen nor t-PA antigen was increased by heparin administration alone. The changes in alpha 2PI and alpha 2PIC levels suggest that fibrinolytic activity is slightly higher in RDT patients and is even higher during HD.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Enhanced fibrinolytic activity during the course of hemodialysis. 138 98

Medroxyprogesterone acetate (MPA), which is widely used clinically as an anticancer steroid preparation, is a very useful drug that seldom causes severe side effects such as bone marrow suppression, and can be dispensed at the outpatient clinic for an oral administration at home to the advantage of QOL. Recently however, there have been several reports suggesting its relationship with thrombosis. We measured t-PA, protein C, factor X, AT III, TAT, plasminogen, PIC, fibrinogen, and D-dimer in 11 patients with gynecologic malignancies who are treated with MPA (600 mg/day) and 11 controls. Then we examined the effects of the drug on blood coagulation and fibrinolytic activities. No changes in these parameters clearly suggested thrombogenesis in either group at this measurement or during the observation period (17 months at the maximum). The present study found no remarkable abnormalities in the blood coagulation and fibrinolytic activities. Thus, to avoid the use of MPA to patients at risk is considered to be the most important precaution for prevention of thrombosis.
 ...
PMID:[Effect of high-dose medroxyprogesterone acetate on coagulative and fibrinolytic factors in patients with gynecological cancers]. 153 83

We examined the hemostatic abnormality of liver disease using hemostatic molecular markers, i.e. TAT, FPA and SFMC for coagulation, B beta 15-42, FDP, D dimer and PIC for fibrinolysis, t-PA and TM for vessel wall. The molecular markers for coagulation were generally increased in cases of liver disease, which was most sensitively reflected by FPA. On the other hand, it was postulated that SFMC was a marker reflecting the complication of DIC in these cases. Hyperfibrinolysis of liver disease was sensitively reflected by the increase of B beta 15-42, and an occasional increase of SFMC or FDP was thought to indicate the complication of DIC in these cases. A high correlation was found between t-PA and TM. It was postulated that the increase of the both markers in liver disease was due to deteriorated clearance by liver dysfunction, although TM is regarded as a marker reflecting endothelial injury. It was expected that visualization of hemostatic disorder of liver disease was made practical with the use of radar chart of these molecular markers.
 ...
PMID:[Analysis of hemostatic abnormality in various disease using molecular-I. Liver disease]. 182 41

I have experienced 35 cases of DIC in my department during last 8 years. These cases were divided into a septic and non-septic groups based on their back-ground, and compared their clinical symptoms and various laboratory findings. The results showed the septic DIC group could be characterized as follows: (1) impairment of the vital organs was more clearly manifested, while hemorrhagic symptoms were mild, (2) the laboratory tests showed almost no tendency for fibrinogen or alpha 2-PI to be decreased or PIC to be increased, (3) the blood PAF (Platelet Activating Factor) level was clearly higher and showed an inverse relationship with the platelet count. On the basis of these clinical findings, I speculated septic DIC involves suppression of secondary fibrinolysis and participation of PAF. In experiment A, I investigated the effects of endotoxin (Et) on the activity of plasminogen activator (PA) in the rabbit renal cortex. In both in vitro and in vivo systems, I could demonstrate the renal cortex PA activity was significantly suppressed by Et. Then, in experiment B, I could confirm, (1) PAF caused a drop in the blood pressure and a decrease in the platelet count that were similar to those induced by Et, and that Et caused a decrease in the platelet count that was inversely accompanied by an increase in PAF, (2) PAF antagonist showed greater efficacy than a protease inhibitor in suppressing the decrease in the blood platelet count.
 ...
PMID:[Clinical and experimental studies of septic DIC in surgical patients, in terms of its characteristic features and pathogenesis]. 787 83

Hypercholesterolemia is associated with an increased incidence of vascular complications. To assess the actual degree of activation of coagulation systems and vascular disorders in hypercholesterolemia, plasma levels of vascular endothelial cell markers, such as thrombomodulin (TM), tissue-type plasminogen activator, plasminogen activator inhibitor-I (PAI-I), and von Willebrand factor, were measured in 51 patients with hypercholesterolemia. We also investigated the effects of Pravastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on plasma lipid, lipoprotein a, and hemostatic markers. The mean plasma levels of thrombin-antithrombin III complex (TAT), fibrinopeptide A (FPA), TM, and PAI-I were significantly elevated in hypercholesterolemia. Of the hemostatic markers, only TM was significantly increased in patients with ischemic heart diseases (IHD). The mean concentration of total cholesterol and levels of TAT, FPA, PAI-I, and TM were significantly reduced after the Pravastatin treatment. The PIC/TAT ratio was significantly increased in non-IHD patients after treatment, this was not the case in IHD patients. These findings suggested the presence of a thrombogenic state and vascular endothelial cell disorders in hypercholesterolemia; such a state might well be related to hypofibrinolysis.
 ...
PMID:Elevated plasma levels of vascular endothelial cell markers in patients with hypercholesterolemia. 826 15

The incidence of early reocclusion is reported to be higher in patients who receive fibrin-specific thrombolytic agents than nonspecific ones. The reason has yet to be clarified. In the present study, we focused on the difference in duration of fibrinolytic activity. The hemostatic parameters of 7 consecutive patients suffering from acute myocardial infarction treated with a fibrin-nonspecific thrombolytic agent (urokinase) were compared with 9 patients who received a fibrin-specific agent (tissue plasminogen activator, t-PA). The plasma concentrations of alpha 2-plasmin inhibitor (alpha 2-PI), plasmin alpha 2-PI complex (PLC), fibrin degradation products E fragment (FDP-E), and D-D dimer (D-dimer) were measured before, soon after, 1, 2, 3, 4, and 6 h and 2, 3, 4, and 7 days after thrombolytic therapy to estimate the hemostatic and fibrinolytic state. A significant decrease in alpha 2-PI (less than the lowest measurable level) with a simultaneous increase in FDP-E and D-dimer was induced soon after the administration of urokinase. FDP-E and D-dimer decreased, with a significant increase in alpha 2-PI, more than 6 h after thrombolytic therapy. In contrast, a less significant decrease in alpha 2-PI with a lesser amount and shorter duration of fibrinolysis were observed in patients who received t-PA. The amount of PIC soon after drug administration was not different between the two groups. Our data suggested that fibrinolytic activities induced by fibrin-nonspecific urokinase persisted longer than expected by its plasma half-life.The fibrinolytic activities might be terminated by the production of alpha 2-PI.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Prolonged activation of fibrinolytic system induced by fibrin nonselective thrombolytic agent can contribute to preventing early reocclusion after coronary thrombolytic therapy. 840 54

In 19 patients with RA and 20 with OA who underwent autotransfusion with unwashed salvaged blood (USB) after total knee arthroplasty, we performed serial measurement of D-dimer, FgDP, t-PA, and PIC in the plasma and salvaged blood. The PIC level at the completion of salvaged blood transfusion was closely correlated with the volume of USB reinfused in the RA group (p<0.001). The t-PA level of salvaged blood showed a significant positive correlation with the total volume of postoperative drainage in both the RA and OA groups (p<0.05). The increase of total postoperative drainage associated with reinfusion of USB is largely caused by an increase of t-PA in the salvaged blood.
 ...
PMID:Activation of fibrinolysis by reinfusion of unwashed salvaged blood after total knee arthroplasty. 1993 82

Photo-Chemo combination therapy has been intensively investigated for treatment of cancers, especially multidrug resistance cancer. However, antagonistic interactions between chemo-drugs and photosensitizers are frequently reported, and drugs doses and treatment sequences have been changed to overcome the problems. We observed the antagonistic effect by a decrease in singlet oxygen generation from the photosensitizer when Dox was in close physical proximity. To control the distance between Dox and the photosensitizer, we developed a novel pH-sensitive poly ionomer complex system composed of PEG-PLL(-g-Ce6) [Chlorin e6 grafted poly(ethylene glycol)-poly(l-lysine)] and PEG-PLL(-g-DMA)-PLA [2,3-dimethylmaleic anhydride grafted poly(ethylene glycol)-poly(l-lysine)-poly(lactic acid)] and evaluated this system with regard to singlet oxygen generation and antiproliferative activity against MCF-7/Dox cells. Enhanced singlet oxygen generation and antiproliferative activities were observed in vitro and in vivo for the poly ionomer complex system compared to PEG-PLL(-g-Ce6)-PLA/Dox due to the change in distance between Dox and Ce6 in the PIC system under acidic conditions. Our results highlight the importance of interactions between co-loaded drugs in combination therapy, and provide new insights into design principles for tailor-made nanomedicine platforms.
 ...
PMID:A nano-complex system to overcome antagonistic photo-chemo combination cancer therapy. 3059 82