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)

In order to describe potential hypofibrinolytic tendencies in young (< 35 years) polycystic ovary syndrome (PCOS) patients, we studied plasminogen activator inhibitor (PAI-1) system components in women without laboratory evidence of hyperinsulinism or hyperandrogenism. The study was a prospective, observational comparison and took place in a major urban infertility referral center. Age, body mass index, ovulatory status, selected androgen levels, fasting insulin and plasma lipids were measured in subjects with PCOS (n = 39) and normal control subjects (n = 20). Women with PCOS had higher mean serum total testosterone and androstenedione levels compared with controls (56.4 versus 40.3 ng/dl, p = 0.03, and 179 versus 133 microg/ml, p = 0.03, respectively). Mean fasting insulin levels were higher among PCOS women (p < 0.01) and were strongly correlated with PAI-1 antigen (Ag) (r = 0.46), PAI-1 activity (r = 0.43), and tissue plasminogen activator (t-PA) (r = 0.5). Correlations were evident in both PCOS and control subjects. Mean PAI-1 Ag, PAI-1 activity, and t-PA levels were significantly elevated (p = 0.003, 0.001, and 0.001, respectively) in PCOS. ANOVA was performed to control for insulin effect; a trend toward elevated PAI-1 in PCOS persisted but was no longer statistically significant (p = 0.24). PAI-1 activity elevation remained in PCOS women with mean fasting insulin levels < 10 mIU/ml (p = 0.02), yet the difference became less significant when insulin was controlled (p = 0.38). Although these data confirm known associations between insulin and PAI-1 derangements, this is the first study to quantify discrete PAI-1 elevations that persist in the setting of PCOS even with normal or low ambient insulin levels. Additional prospective studies are needed to determine whether this altered PAI-1 state is associated with a clinically important hypofibrinolytic condition and subsequent poor reproductive outcome.
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PMID:Absence of profound hyperinsulinism in polycystic ovary syndrome is associated with subtle elevations in the plasminogen activator inhibitor system. 1285 31

There is a common belief in a class effect among angiotensin-converting enzyme (ACE) inhibitors. This is unsubstantiated for acute myocardial infarction (AMI). Because vascular tissue is a source of the endogenous fibrinolytic markers, and ACE inhibition in vascular tissue favorably influences the fibrinolytic system, the authors hypothesized that a high-tissue-penetrating ACE inhibitor would provide a more favorable reduction in plasminogen activator inhibitor-1 (PAI-1) and an increase in tissue plasminogen activator (t-PA) after AMI compared to a low-tissue-penetrating ACE inhibitor. In a randomized open-label trial, patients received the high-tissue-penetrating quinapril (n = 15) or low-tissue-penetrating enalapril (n = 15) immediately following an AMI. PAI-1 and t-PA antigen (ng/mL) were measured at baseline and through 14 days of treatment. There was no difference in baseline PAI-1 or t-PA antigen between treatments. PAI-1 antigen trended toward being lower with quinapril versus enalapril on day 1 (24.44 +/- 14.96 vs. 36.94 +/- 19.49, respectively, p = 0.059) and was significantly lower on day 3 (17.32 +/- 9.57 vs. 27.49 +/- 9.61, respectively, p = 0.009). Analysis of PAI-1 antigen over time by two-factor ANOVA with replication found significantly lower concentrations of PAI-1 antigen over the entire treatment period with quinapril versus enalapril (p < 0.003). This investigation of ACE inhibitor tissue-penetrating influence on markers of reinfarction risk suggests there may be a greater early reduction in PAI-1 with a more highly tissue-penetrating ACE inhibitor.
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PMID:Questioning a class effect: does ACE inhibitor tissue penetration influence the degree of fibrinolytic balance alteration following an acute myocardial infarction? 1474 23

Phospholipid-derived mediators are implicated in the initiation and progression of human labor and delivery, particularly in relation to infection-induced preterm labor. We previously demonstrated that, in human intrauterine tissues, lipopolysaccharide (LPS)-stimulated nuclear factor-kappaB (NF-kappaB) DNA binding activity, and subsequent cytokine release can be suppressed by sulfasalazine (SASP) concentrations greater than 5 mM. The aim of this study was to elucidate the effect the SASP on secretory type II phospholipase A(2) (PLA(2)), cytosolic PLA(2) (cPLA(2)), cyclooxygenase (COX) isozymes, and subsequent prostaglandin F(2alpha) (PGF(2alpha)) production in human gestational tissues. Human placenta, amnion, and choriodecidua (n = 4-9 separate placentas) were incubated in the presence of SASP (0.1, 1, 5, and/or 10 mM) under either basal or LPS (10 microg/ml) conditions. After 6 h incubation, the tissues were collected and assayed for type II PLA(2) by ELISA and cPLA(2), COX-1, and COX-2 content by Western blotting. The incubation medium was collected and assayed for type II PLA(2) and 13,14-dihydro-15-keto PGF(2alpha) release by ELISA and PGF(2alpha) by RIA. Treatment of placenta, amnion, and choriodecidua with SASP concentrations greater than 5 mM significantly inhibited basal and/or LPS-stimulated type II PLA(2) content and release, 13,14-dihydro-15-keto PGF(2alpha) release, and cPLA(2) protein content (ANOVA, P < 0.05); however, no effect of SASP was observed on basal or LPS-stimulated COX-1 or COX-2 protein. Although no effect of SASP was observed on basal and LPS-stimulated PGF(2alpha) release from placenta and amnion, it significantly increased both basal and LPS-stimulated PGF(2alpha) release from choriodecidua. In addition, SASP concentrations of 5 mM or greater significantly suppressed NF-kappaB DNA binding activity. These data are consistent with the hypothesis that NF-kappaB regulates the expression and release of phospholipase isozymes.
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PMID:Regulation of phospholipase isozymes by nuclear factor-kappaB in human gestational tissues in vitro. 1512 65

Blood flow and plasma fibrinolytic factors were measured on five occasions in both forearms of eight otherwise healthy male smokers during unilateral brachial artery infusion of the endothelium-dependent vasodilator, substance P (2 to 8 pmol/min), and the endothelium-independent vasodilator, sodium nitroprusside (2 to 8 microg/min). On the first occasion, intra-arterial vitamin C was co-infused at 25 mg/min. On subsequent occasions, subjects attended after 28 and 35 days treatment with oral vitamin C (1 g daily) or placebo in a double-blind randomized crossover design still smoking but with and without acute smoke inhalation (3 cigarettes over 30 minutes). Basal plasma ascorbate concentrations increased from 37 +/- 6 micromol/L to 105 +/- 11 micromol/L following oral vitamin C supplementation (P = 0.002). Substance P caused dose-dependent increases in forearm blood flow (P < 0.001, ANOVA) and t-PA release (P < 0.05, ANOVA) that was unaffected by acute recent smoke inhalation, intra-arterial vitamin C, or oral vitamin C administration (p = ns). Likewise there were no effects on sodium nitroprusside-induced vasodilatation (p = ns). Neither acute local intra-arterial nor prolonged oral vitamin C supplementation reverses smoking-related endothelial dysfunction and impaired endogenous t-PA release. We conclude that the adverse vascular actions of smoking are not principally mediated through oxidative stress.
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PMID:Vitamin C has no effect on endothelium-dependent vasomotion and acute endogenous fibrinolysis in healthy smokers. 1517 66

We have shown that the capacity for local release of tissue-type plasminogen activator (tPA) from the vascular endothelium is impaired in patients with primary hypertension. Because this response is an important protective mechanism against intravascular clotting, we investigated whether this system is also defective in patients with advanced chronic kidney disease and hypertension. Nine nondiabetic nonsmoking men with chronic kidney disease (glomerular filtration rate 11 to 28 mL/min x 1.73 m2; aged 33 to 75 years) were compared with age-matched healthy controls. Intraarterial infusions of desmopressin, methacholine, and sodium nitroprusside were given locally in the brachial artery. Forearm blood flow was measured by venous occlusion plethysmography and blood collected repeatedly during the desmopressin infusion for determination of stimulated net and total cumulated release of tPA. The maximal release rate of active tPA (P<0.05) and the capacity for acute tPA release were markedly impaired in the renal patients as compared with healthy subjects (ANOVA, P=0.013). Accordingly, the accumulated release of tPA was 1905 (SEM 366) and 3387 (718) ng/L tissue, respectively (P<0.05). However, there were no significant differences in vasodilator responses between the groups. Thus, patients with advanced chronic kidney disease and hypertension have a markedly impaired capacity for acute release of tissue plasminogen activator, despite preserved endothelium-dependent vasodilation. This defect may contribute to a defective local defense against arterial thrombosis.
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PMID:Impaired endothelial release of tissue-type plasminogen activator in patients with chronic kidney disease and hypertension. 1524 48

Thrombus formation within hemodialysis catheters contributes to inadequate dialysis and adverse patient outcomes. A thrombolytic agent may be required to restore patency and improve blood flow. This study evaluates the efficacy of instilling low dose (1 mg/ml) t-PA in catheter lumens to restore patency in malfunctioning catheters. t-PA was utilized to treat suspected catheter thrombus over a four-month period. Seventeen patients with 21 catheters (12 temporary, 9 permanent) received 40 doses of t-PA. Catheter function was restored in 39 of 40 cases (97.5%). Significant improvement in blood flow was confirmed by paired t-test (p < 0.001). Sustained improvement in blood flow was confirmed by ANOVA (p < 0.001). The mean primary patency of all catheters was 29.7 days (SD = 27.0 days). No adverse patient effects were noted. These results demonstrate that t-PA can safely and effectively restore blood flow and extend patency in hemodialysis catheters.
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PMID:Tissue plasminogen activator (t-PA) efficacy in the restoration of hemodialysis catheter function. 1571 85

The increased risk for myocardial infarction and ischemic stroke in primary hypertension suggests that the condition is associated with prothrombotic mechanisms. We have shown that patients with hypertension have an impaired capacity for acute endothelial tissue-type plasminogen activator (t-PA) release, an important local protective response to prevent formation of intravascular thrombi. The aim of the present study was to investigate whether this impairment could be restored by the lowering of blood pressure. The capacity for acute t-PA release in response to intraarterial infusion of substance P at 8 pmol/min was investigated in a perfused-forearm study in 20 hypertensive patients (12 men and 8 women). Studies were performed when patients were untreated and after 8 weeks of randomized treatment with lisinopril or felodipine that lowered blood pressure by 26/10 and 24/12 mm Hg, respectively. The t-PA release response increased significantly with treatment (ANOVA, P=0.0001), with a similar effect in the 2 treatment groups. The peak release of t-PA increased from 257 (58) to 445 (77) ng/min x L/tissue(-1) (t test, P=0.02). Also, treatment shortened the average time to peak secretion from 6.7 (1.4) to 2.7 (0.3) min (t test, P=0.01). In 6 patients with a delayed secretory peak (9 minutes or later), treatment normalized the response (chi2 test, P=0.008). Antihypertensive therapy restores the capacity for acute t-PA release and improves the rapidity of the response in patients with primary hypertension. Similar responses with the 2 regimens suggest that the improvement is related to the blood pressure reduction as such. This effect may contribute to the thromboprotective effect of antihypertensive treatment.
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PMID:Impaired capacity for stimulated fibrinolysis in primary hypertension is restored by antihypertensive therapy. 1652 Apr 4

We hypothesized that restenosis after coronary stenting is predicted by elevated levels of markers of thrombus formation and inflammation. Plasma levels of representative markers of inflammation, the thrombin and plasmin activation systems and adhesion molecules were measured in 59 patients with stable angina pectoris before, immediately after and 6 hours (h), 12 h, 24 h, one month and six months after elective stent implantation (radioactive phosphorus-32 stents/RSs/ n = 16, bare-metal stents/BMSs/ n = 43). All patients underwent clinical and angiographic follow-up (FUP) six months after stenting. RSs had significantly higher angiographic severity of restenosis than BMSs (47.1 +/- 20.1% vs. 27.6 +/- 22.0%, p = 0.003). Repeated measures ANOVA revealed significant differences between the BMS and RS groups as regards the increases in plasma levels of vascular cell adhesion molecule-1 (VCAM-1, p = 0.022), plasminogen activator inhibitor-1 (PAI-1, p = 0.047), tissue-type plasminogen activator (tPA, p = 0.047) and CD40 ligand (CD40L, p = 0.038). tPA levels tended to increase immediately after stenting in both groups, whereas the PAI-1 level one month after stenting was elevated significantly only in the RS group. In the RS group, the plasma levels of CD40L were increased at 24 h and six months after stenting, and the VCAM-1 level rose immediately after stenting and remained high during the FUP. Multivariate analysis on pooled laboratory data of both groups revealed elevated levels of VCAM-1 at 12 h and at six months as significant predictors of the severity of stent restenosis. In conclusion, the process of inflammation and thrombosis occurring after coronary interventions seems to be prolonged and enhanced in patients with high-grade restenosis at the follow up.
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PMID:Time course of prothrombotic and proinflammatory substance release after intracoronary stent implantation. 1839 32

Oral supplementation with bovine colostrum (COL) has been shown to enhance immunity in human subjects. However, there is limited research on the use of bovine COL supplementation to counter exercise-induced immunodepression, as a model of stress-induced immunodepression, and previous research has focused primarily on salivary IgA. The aim of the present study was to determine the effects of bovine COL supplementation on exercise-induced changes in innate immunity (neutrophil function and salivary lysozyme) in addition to salivary IgA. Twenty healthy, active men cycled for 2 h at approximately 64 % maximal oxygen uptake after 4 weeks of daily bovine COL (n 10) or placebo (PLA, n 10) supplementation. Blood and saliva samples were obtained before and after supplementation, before and after exercise. Exercise induced significant increases in markers of physiological stress and stress to the immune system (circulating neutrophils, neutrophil:lymphocyte ratio, immature granulocytes, atypical lymphocytes and plasma cortisol), but there were no differences between the COL and PLA groups. Significant group x time interactions (two-way mixed model ANOVA) were observed for neutrophil function (stimulated degranulation) and salivary lysozyme concentration and release (P < 0.05). Significant exercise-induced decreases were observed in these parameters, and bovine COL supplementation either speeded the recovery (neutrophil function) or prevented the decrease (salivary lysozyme) in these measures of innate immunity. These results suggest that 4 weeks of bovine COL supplementation limits the immunodepressive effects induced by an acute prolonged physical stressor, such as exercise, which may confer some benefits to host defence.
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PMID:Bovine colostrum supplementation attenuates the decrease of salivary lysozyme and enhances the recovery of neutrophil function after prolonged exercise. 2003 Sep 5

The olfactory bulbectomized rat is an animal model of depression with a number of neurochemical, neuroendocrinological and behavioural features resembling human depression. Arachidonic acid (AA) is a second messenger released from the neuronal membrane phospholipids following the stimulation of the receptors coupled with G-proteins to the cytosolic phospholipase A (cPLA(2)) signalling pathway. The signalling of several neurotransmitter systems which are deregulated in OBX rats (serotonergic, dopaminergic, cholinergic, and glutamatergic) converges on the cPLA(2) signalling pathway. The aim of the present study was to assess the incorporation coefficient k* [ml/g/s] of AA in a large number of brain regions in the OBX rat, as a parameter reflecting AA turnover. Male Sprague-Dawley rats (160-200 g) were randomly assigned into an intact Sprague-Dawley (SPD) group, a Sham-operated (SHAM) group or an olfactory bulbectomized (OBX) group (n=5 per group). Two weeks following the surgeries (SHAM and OBX rats) or without any prior intervention (SPD rats), the k* was measured using [1-(14)C] AA autoradiography. Two-way ANOVA followed by the Newman-Keuls test revealed the following: (1) significantly increased AA turnover in the OBX rats, relative to the SHAM rats, in 17 out of 27 assessed brain regions; and (2) no significant differences in AA turnover between the SHAM and the SPD rats. The results suggest the upregulation of one or more neurotransmitter systems or receptors acting through the PLA(2) signalling pathway, or the components of the cPLA(2) signalling system itself. Taken together with the previous measurements, one can conclude that this elevation is likely related to upregulation in the brain serotonergic system because of the elevated 5-HT synthesis of the OBX rats.
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PMID:Upregulated arachidonic acid signalling in the olfactory bulbectomized rat model of depression. 2121 42


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