Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The plasma thrombomodulin (TM) level depends on the integrity of the endothelium and the clearance of the molecule. In several different pathological conditions, plasma TM levels increase with damage to the endothelium. We studied plasma TM levels in patients with various localizations of atheromatous arterial disease who had normal serum creatinine levels. Two groups of patients had a single symptomatic localization, which was either peripheral occlusive arterial disease (POAD) or ischemic heart disease (IHD) and a third group of patients had multiple symptomatic localizations (polyvascular). We compared the plasma TM levels with the plasma levels of other specific markers of endothelial cell activation such as: prostacyclin (PGI2), tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1). Plasma TM levels were significantly increased in all three individual groups and when all patients were considered (total patients), as compared with normal controls. When all patients were considered, there was a significant positive correlation between plasma TM levels and t-PA and between plasma TM levels and PGI2. A significant positive correlation was also found between the plasma TM levels and PAI-1 for patients with POAD. Thus, our findings suggest that an increased influx of TM into the plasma may be caused by endothelial cell damage in patients with atheromatous arterial disease. However in our study, the plasma TM levels obtained were similar for all three types of atheromatous arterial disease. Though plasma thrombomodulin is a marker of endothelial cell injury, it cannot be of a clinical interest until its levels are related to the extend of the atheromatous lesions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Levels of plasma thrombomodulin are increased in atheromatous arterial disease. 813 3

Fibrinolytic parameters and von Willebrand factor (VWF) antigen were measured in 22 patients with glomerulonephritis (GN) who underwent renal biopsy after desmopressin (DDAVP) infusion. Blood was collected immediately before and after DDAVP infusion, after one week, and 3-6 months later. The main abnormalities on admission were the following: the mean baseline levels of t-PA antigen and VWF were significantly higher in GN patients than in 22 healthy controls; the median t-PA activity and the mean scu-PA level were significantly lower than normal. The t-PA response to DDAVP was impaired in 7 patients (32%), the response of VWF in 9 patients (41%), and the u-PA:Ag response in 11 patients (50%). When the patients were stratified according to creatinine clearance rate, significant differences between the subgroups with severely and moderately impaired renal function were noted: the baseline levels of PAI activity and VWF were higher in patients with severe renal failure and the VWF response to DDAVP was significantly lower. The response of u-PA (not of t-PA or VWF) to DDAVP appeared to correlate with urine flow during the first 24 h, suggesting the dependence of u-PA release on intact nephrons. A series of 18 patients with adult-type polycystic kidney disease (APKD) with creatinine clearance rates in the same abnormal range as the GN patients, had lower mean PAI and a significantly higher mean scu-PA level.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Blood fibrinolysis and the response to desmopressin in glomerulonephritis. 816 42

A 46-year-old housewife with regurgitation of mitral valve developed acute renal failure due to acute thrombosis of bilateral renal arteries after cardiac catheterization. A regional fibrinolytic therapy using transarterial infusion of tissue plasminogen activator (t-PA) was performed at 8 h after the onset, and was successful. She could be taken off hemodialysis 2 weeks after the fibrinolytic therapy, and could be successfully operated on with mitral valve replacement 7 months after that. Three years after mitral valve replacement, her serum creatinine was 148 mumol/l. This is the longest follow-up case after regional transarterial fibrinolysis of acute thrombosis of renal artery using t-PA, and this therapy is a safe and good one for acute thrombosis of renal artery.
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PMID:Successful fibrinolytic therapy using tissue plasminogen activator in acute renal failure due to acute thrombosis of bilateral renal arteries. 824 31

Poly(D,L-lactide) microspheres loaded with cisplatin (PLA-CDDP MS) were prepared by a solvent evaporation technique for direct intratumoral injection. The microspheres, 50-100 microns, containing 40.04% of cisplatin produce sustained release in vitro. PLA-CDDP MS (6 mg/kg body weight of cisplatin) suspensions were injected intratumorally into mammary tumors in rats. Cisplatin solution (6 mg/kg body weight) was injected either intratumorally or intraperitoneally in two groups. After treatments, the tumor size decreased in each of the groups as a function of time. Sixteen days post-injection, the tumors had either disappeared or significantly shrunk. PLA-CDDP MS had a similar antitumor effect compared with cisplatin aqueous solution. Blood urea nitrogen, serum creatinine and histopathology examinations revealed that the renal toxicity in the PLA-CDDP MS group was significantly less than in the control groups. These results indicate that intratumoral injection of PLA-CDDP MS maintains anticancer potency and reduces acute renal toxicity.
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PMID:Percutaneous intratumoral injection of cisplatin microspheres in tumor-bearing rats to diminish acute nephrotoxicity. 874 Jul 29

We examined the effect of a specific thrombin inhibitor, Ro 46-6240, alone and combined with an antagonist of the platelet GP IIb/IIIa, Ro44-9883, on the response to tissue-type plasminogen activator in a canine model of thrombolysis. Platelet activity was determined by measuring the excretion of 2,3-dinorthromboxane (TX)B2, an enzymatic metabolite of TXA2. Ro 46-6240 administered before tissue-type plasminogen activator induced a dose-dependent prolongation of the activated partial thromboplastin time and prothrombin time. The time to reperfusion decreased dose-dependently (P < .01) to 10 +/- 6 min vs. 52 +/- 5 min in controls. Ro 46-6240 also prevented reocclusion, which occurred in every case in control experiments. Urinary excretion of 2,3-dinor-TXB2 increased from 3 +/- 1 to 37 +/- 9 ng/mg creatinine in controls after reperfusion. This increase was reduced in a dose-dependent fashion by Ro 46-6240, such that at the highest dose, urinary 2,3-dinor-TXB2 after reperfusion was 5.6 +/- 1 ng/mg creatinine. Similar functional and biochemical effects were seen when a subthreshold dose of Ro 46-6240 was combined with Ro 44-9883. At the dose used, Ro 44-9883 alone abolished platelet aggregation ex vivo but failed to modify the response to tissue-type plasminogen activator or the excretion of 2,3-dinor-TXB2 after reperfusion (51 +/- 6 ng/mg creatinine, n = 3). However, the combination of Ro 44-9883 and Ro 46-6240 reduced the time to reperfusion (40 +/- 8 vs. 68 +/- 15 min; n = 7, P < .05), prevented reocclusion and abolished the rise in urinary 2,3-dinor-TXB2 (5 +/- 1 ng/mg creatinine, n = 4). These findings suggest that thrombin mediates platelet activation during coronary thrombolysis. The increased platelet activity results in platelet aggregation and a subsequent increase in TXA2 formation.
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PMID:Interaction of a thrombin inhibitor and a platelet GP IIb/IIIa antagonist in vivo: evidence that thrombin mediates platelet aggregation and subsequent thromboxane A2 formation during coronary thrombolysis. 919 Aug 51

RGD-containing peptides and other antagonists of the platelet glycoprotein (GP) IIb/IIIa may induce a high-affinity binding site for fibrinogen and the expression of novel epitopes, called ligand-induced binding sites (LIBS). The functional relevance of LIBS expression in a canine model of coronary thrombolysis induced by tissue-type plasminogen activator (t-PA) was examined. Ro43-5054 (N-[N-[N-(p-amidinobenzoyl)-b-alanyl]-l-a-aspartyl]-3-phenyl-l- alanine) and Ro44-9883 ([1-(N-(p-amidinobenzoyl)-l-tyrosyl)-4-piperidinyl)oxy]acetic acid), antagonists of the GP IIb/IIIa receptor, were administered in increasing doses of 2 to 10 microg/kg/min, beginning 30 min before the infusion of t-PA. LIBS expression was determined by the binding of the monoclonal antibody, D3GP3, to platelets on exposure to Ro43-5054, Ro44-9883 and t-PA. Ro43-5054 was shown to induce LIBS, whereas Ro44-9883 and t-PA did not. Both drugs abolished platelet aggregation in response to U46619 and ADP ex vivo. Reocclusion was prevented with both Ro43-5054 and Ro44-9883, but neither drug altered reperfusion times (49 +/- 8 and 55 +/- 39 min). Both drugs increased the rate of bleeding compared with t-PA alone, but there was no difference in hemostasis between the two drugs. To determine whether the drugs differed in their effect on platelet activation in vivo, urinary 2,3-dinor-thromboxane (TX) B2, a major metabolite of TXB2, was determined by gas chromatography-mass spectrometry. After reperfusion, the urinary 2,3-dinor-TXB2 increased in the Ro43-5054-treated group, similar to control groups (32 +/- 8 and 37 +/- 9 ng/mg creatinine). This increase was blunted in the Ro44-9883-treated group (9 +/- 3 ng/mg creatinine). GP IIb/IIIa antagonists that do not induce LIBS result in a greater suppression of platelet activity but not in any discernible functional benefit in vivo.
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PMID:Functional relevance of the expression of ligand-induced binding sites in the response to platelet GP IIb/IIIa antagonists in vivo. 969 54

In 12 operatively (stereotactic aspiration and recombinant tissue-type plasminogen activator, rTPA) and 5 conservatively treated patients with spontaneous intracerebral hemorrhage the amounts of cysteinyl-leukotriene (cys-LT) released by blood-brain cell contact were measured by the urinary excretion of their metabolites during treatment. The mean cys-LT release before treatment was 14.51 +/- 1.13 pg/mg creatinine/ml hematoma volume. The urinary cys-LT excretion at the end of the measurements was significantly lower in the operatively treated group than in the patients with conservative therapy (p < 0.05). We also found a significant correlation between the perifocal edema volume and the amount of cys-LT measured in patients' urine (p < 0.01). In an additional animal experiment using dissociated rat brain cells plasmin was excluded as an activator for cerebral cys-LT formation, which emphasizes that rTPA did not influence cys-LT formation.
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PMID:Cysteinyl-leukotriene levels in intracerebral hemorrhage: an edema-promoting factor? 977 48

Cyclosporin A (CsA) has been implicated as one of the factors contributing to the high cardiovascular morbidity and mortality after renal transplantation. This may be mediated by either a high prevalence of conventional risk factors for atherosclerosis, such as hypertension, hypercholesterolemia, and diabetes mellitus, or by impairment of the fibrinolytic activity evoked by CsA, possibly through interference with prostanoid metabolism. We therefore assessed the impact of conversion of CsA to azathioprine immunosuppressive treatment on parameters of fibrinolytic activity and plasma concentration of the prostanoids prostaglandin E2 and thromboxane B2 in 18 stable renal transplant recipients. During CsA, mean arterial pressure and serum creatinine were significantly higher than during azathioprine (116+/-15 mm Hg versus 106+/-13 mm Hg, P=0.0003; and 147+/-34 micromol/L versus 127+/-35 micromol/L, P=0.002; mean+/-SD). On conversion, the plasma tissue plasminogen activator activity increased from 1.2 (1.1 to 1.7; median, 95% CI) to 1.8 (1.6 to 2.0) IU/mL (P=0.011), without a significant change of the plasminogen activator antigen concentration. This was associated with a substantial decrease in plasminogen activator inhibitor-1 activity from 10.4 (8.5 to 16.7) to 6.4 (5.6 to 9.2) IU/mL (P=0.009). Furthermore, plasma levels of prostaglandin E2 and thromboxane B2 markedly decreased (from 9.7 [7.4 to 12.9] to 4.6 [4.3 to 8.1] pg/mL, P=0.0006; and from 106.1 [91.7 to 214.2] to 70.2 [50.3 to 85.6] pg/mL, P=0.002, respectively). During CsA, but not azathioprine, plasma tissue plasminogen activator antigen and plasminogen activator inhibitor-1 levels correlated significantly with prostaglandin E2 (r=0.53, P=0.02; and r=0.60, P=0.008, respectively), and thromboxane B2 (r=0.75, P=0.0001; and r=0.77, P=0.0001, respectively) levels. In conclusion, CsA induced substantial impairment of fibrinolytic activity, which recovered after conversion to azathioprine. The impaired fibrinolysis observed during CsA treatment may be caused by modulation of eicosanoid production or metabolism in vascular endothelial cells and possibly contributes to the high incidence of cardiovascular disease after kidney transplantation.
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PMID:Beneficial effects of conversion from cyclosporine to azathioprine on fibrinolysis in renal transplant recipients. 1036 89

Clinical effects of recombinant human erythropoietin (rHuEPO) such as thrombosis, convulsions, hyperviscosity, hypertension, and angiogenic effect in culture cells have been described. We studied the rHuEPO effect on endothelial damage markers and endothelial function markers: tissue-type plasminogen activator (t-PA), nitrate (NO3), thrombomodulin (TM), and von Willebrand factor (vWF). Twenty-six peritoneal dialysis patients treated with rHuEPO and 19 controls were included. The study design for rHuEPO patients consisted of four periods: long-term treatment (rHuEPO-1); 2 months of withdrawal (rHuEPO-2); and 4 months on 5000 IU/week rHuEPO subcutaneously, with markers being measured after 2 months (rHuEPO-3) and after 4 months (rHuEPO-4). After 2 months of rHuEPO withdrawal, a decrease in hemoglobin level appeared (11+/-1.8 g/dL to 9.2+/-1.5 g/dL, p < 0.01). After rHuEPO reintroduction, this value reached 10.6+/-1.5 g/dL at two months, and 11.1+/-1.4 g/dL at four months. A significant increase in t-PA ratio was observed from two months without rHuEPO to two months on rHuEPO, returning to previous values after four months. Similarly, TM increased for patients with creatinine clearances (CrC) < 5 mL/min. No changes in the higher-than-normal plasma vWF levels were found during the various periods. A statistically significant lower value was found in controls compared with rHuEPO-4 patients. A statistically significant increase in NO3 levels was observed in the pre-venous occlusion (VO) test immediately after the re-introduction of rHuEPO. This increment returned to prior values four months after rHuEPO was reintroduced. Our results show that rHuEPO treatment causes an increase in some endothelial damage markers (TM, t-PA) and modifies endothelial function markers (t-PA ratio, NO3). These changes might favor thrombosis and atherosclerosis.
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PMID:Effects of recombinant human erythropoietin on functional and injury endothelial markers in peritoneal dialysis patients. 1040 11

We have previously demonstrated that gentamicin-induced acute renal failure is mediated by the consumption of renal glutathione (GSH) and accumulation of oxidized phospholipids in tubular epithelial cells as a result of inhibition of phospholipase A(2) (PLA(2)) activity. Based on these results, we tested the hypothesis that the simultaneous inhibition of PLA(2) and GSH synthesis induces acute renal failure similar in characteristics to gentamicin-induced acute renal failure. Male Sprague-Dawley rats kept under standard laboratory conditions were administered 3 mmol/kg of DL-buthionine sulfoximine (BSO; gamma-glutamylcysteine synthetase inhibitor) and 30 microg/kg of manoalide (PLA(2) inhibitor), following which significant elevations in serum creatinine and urinary lysosomal enzyme levels (elevation of N-acetyl-beta-D-glucosaminidase activity) were observed. The renal tissue GSH content was reduced in the group that received both BSO and manoalide as compared with the group that received manoalide alone. The renal tissue GSH content was also reduced in the group that received BSO alone. The renal tissue concentration of 2-thiobarbituric-acid-reactive substances increased rapidly, followed by an increase in renal tissue total phospholipid concentration in the group that received both BSO and manoalide. In contrast, the activity of PLA(2) in renal tissue decreased in the group that received both BSO and manoalide as compared with the groups that received BSO alone or physiological saline. In conclusion, concomitant administration of BSO and manoalide induces renal tubular damage and acute renal failure in rats, similar in characteristics to gentamicin-induced nephrotoxicity, whereas administration of BSO or manoalide alone did not. These results suggest that both inhibition of PLA(2) and GSH depletion are necessary for the induction of acute renal failure.
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PMID:Simultaneous inhibition of renal phospholipase A(2) and glutathione synthesis by manoalide and DL-buthionine sulfoximine induces acute tubular dysfunction in rats. 1072 47


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