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)

To study fibrinolysis in relation to microvascular diabetic complications, 20 control subjects were compared with 50 Type 1 (insulin-dependent) diabetic patients of similar age, 20 with no complications, 17 with laser-treated retinopathy, and 13 with neuropathy and retinopathy. None were smokers, hypertensive or had macrovascular disease. Pre- and post-venous occlusion blood samples for tests of fibrinolysis were taken. Median (interquartile range) basal tissue plasminogen activator (t-PA) activity was lower in control subjects (100 (less than 100-100) IU l-1) than diabetic patients (uncomplicated 145 (100-280) IU l-1, p = 0.015; retinopathy 180 (100-228) IU l-1, p = 0.037; neuropathy 210 (125-310) IU l-1, p = 0.004, respectively). Basal t-PA inhibition (PAl-1 activity) was higher in control subjects (5.9 (4.5-9.5) kIU l-1) than diabetic patients (uncomplicated 4.0 (3.3-5.0) kIU l-1, p = 0.001; retinopathy 4.5 (3.1-6.3) kIU l-1, p = 0.058; neuropathy 4.0 (3.0-5.4) kIU l-1, p = 0.015, respectively). Post-venous occlusion t-PA antigen was higher in control subjects (10.2 (7.3-15.1) micrograms l-1) than neuropathic patients (5.5 (4.9-7.3) micrograms l-1, p = 0.004). Other tests showed a consistent, but non-significant, trend towards increased basal fibrinolysis in the Type 1 diabetic patients. The results indicate that Type 1 diabetic patients have enhanced basal fibrinolysis. The diminished response to venous occlusion in neuropathic patients is consistent with an endothelial cell defect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Contrasting fibrinolytic responses in type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes. 183 48

The present study was performed to elucidate the acute effect of insulin on levels of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor of endothelial cell type (PAI-1). Nine middle-aged, non-obese and non-smoking men were studied during a hyperinsulinemic, euglycemic glucose clamp for 2 h. Plasma insulin level during the clamp averaged 84 +/- 12 mU/l and euglycemia was maintained at 4.9 +/- 0.6 mmol/l. The t-PA activity gradually increased (75% mean increase after 2 h, p less than 0.001) and the PAI-1 activity decreased (49% mean decrease after 2 h, p less than 0.001) during the clamp. t-PA activity decreased and PAI-1 activity increased after the insulin infusion was ceased, but they were still 48% higher and 38% lower, respectively, after 60 min. PAI-1 and t-PA activities were not affected by saline infusion for 2 h. Thus, acute changes in the insulin levels lead to rapid alterations in the fibrinolytic system even when euglycemia is maintained. These effects may be induced by insulin itself or by the concomitant activation of the sympatho-adrenal system during the euglycemic clamp.
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PMID:The acute effect of insulin on tissue plasminogen activator and plasminogen activator inhibitor in man. 190 68

This study examined the effect of gliclazide on tissue-type plasminogen activator (t-PA)-related fibrinolysis in 23 Type I diabetic patients without residual beta-cell function and 17 Type II diabetic patients initially treated with tolbutamide. The Type I diabetic patients received gliclazide for a period of 6 months; the Type II diabetic patients were shifted from tolbutamide to gliclazide. In Type I diabetic patients, after 2-3 months of treatment with gliclazide, we observed a significant increase in plasma concentrations of total t-PA antigen that remained stable until discontinuation of the drug (p less than 0.0002), whereas the plasma concentrations of plasminogen activator inhibitor (PAI) did not change significantly during the study. Next, we investigated the possibility of gliclazide inducing t-PA-related fibrinolysis in a subset of Type II diabetics without detectable concentrations of t-PA during treatment with tolbutamide. The concentrations of active t-PA increased significantly 3 months after a change in treatment to gliclazide, and active t-PA again decreased in one patient to undetectable levels after 12 months with gliclazide. Moreover, the plasma concentrations of total t-PA antigen increased significantly (p less than 0.02) in this group of diabetic patients while PAI remained unchanged. The changes in t-PA-related fibrinolysis could not be related in either Type I or Type II diabetics to changes in metabolic state evaluated by blood glucose, HbA1c, cholesterol, triglycerides, or apolipoproteins A and B. We conclude that gliclazide has the potential to exert extrametabolic non-insulin-mediated effects on t-PA-related fibrinolysis in diabetic patients.
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PMID:Increased fibrinolytic potential induced by gliclazide in types I and II diabetic patients. 190 83

The duration of preincubation of aspirated oocytes is essential for successful in vitro fertilization. The duration has to be varied according to the maturity of the oocyte and the follicle. The maturity of the oocyte corona-cumulus complex is assessed primarily by light microscopy. Additional information is provided by measurements of steroids, pituitary hormones, and proteins (such as inhibin, alpha 1-Antitrypsin, fibrinogen, plasminogen activator, collagenolytic enzymes, alpha 2-macroglobulin, fibronectin, glycosaminoglycans, insulin, insulin-like-growth-factors) in the follicular fluid. Complex measurements of so-called regulators of oocyte maturation (cAMP, oocyte maturation inhibitor, prostaglandins) is of high academic interest. Cytologic parameters, the chemotactic activity of the granulosa cells and serial ultrasound studies are of practical importance for evaluating the maturity of the growing follicle.
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PMID:[Criteria of the maturity of follicle and oocyte within the scope of in vitro fertilization. An overview]. 204 77

An inadequate efficiency of the fibrinolytic system was revealed in 50-60% of subjects suffering young age from venous thrombosis or myocardial infarction. In a group of 27 patients with the history of deep venous thrombosis of the idiopathic type the authors revealed a significant relationship between the elevated body weight and inadequate fibrinolysis manifested by a reduced fibrinolytic capacity and excess inhibitor of plasminogen activator and its inadequate decline after desmopressin infusion (DDAVP). In a group of 29 patients, who had suffered a myocardial infarction when young, the authors revealed a significant association between reduced fibrinolytic capacity and elevated body weight, hypertriglyceridaemia and increased immunoreactive insulin secretion after a glucose load. In half the investigated subjects it proved possible to improve the reduced fibrinolytic capacity by a low energy diet.
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PMID:[Disorders of fibrinolysis and thrombophilic states, risk factors and possibilities of dietary effects]. 205 93

To evaluate possible hormonal regulators of the diurnal rhythm in fibrinolytic activity, we measured tissue plasminogen activator (t-PA) activity, plasminogen activator inhibitor activity (PAI-1), t-PA antigen, insulin, cortisol, and catecholamines in 6 healthy males (age 34 +/- 5) every 2 hours for 24 hours. Fibrinolysis was characterized by a peak in PAI-1 activity and a trough in t-PA activity at 0600 h. PAI-1 activity increased 92% and t-PA activity decreased 56% between 2400 h and 0600 h. t-PA antigen (principally a measure of t-PA/PAI-1 complex), peaked at 0800 h. In comparison, insulin levels were lowest at night when PAI-1 activity was rising. The weak inverse correlation between insulin and PAI-1 activity (r = -0.28, p less than 0.02), was not sufficient to explain the diurnal change in fibrinolysis. While cortisol demonstrated the expected circadian change, the increase in cortisol did not occur until 0400 h, 4-6 hours after the rise in PAI-1 and decrease in t-PA activity started. Supine resting plasma epinephrine and norepinephrine showed no circadian rhythm. From this data, we hypothesize that the increased level of PAI-1 in the morning consumes t-PA, leading to decreased t-PA activity and increased t-PA/PAI-1 complex. Further, we conclude that insulin, cortisol, and catecholamines are not responsible for the circadian rhythm of fibrinolysis.
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PMID:Insulin, cortisol and catecholamines do not regulate circadian variations in fibrinolytic activity. 211 89

Parameters of fibrinolysis, including plasminogen, alpha 2 plasmin-inhibitor (alpha 2 PI), tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) antigens, and fibrinogen were assayed in 53 patients (28 women and 27 men; mean age: 64 years, age range: 32-87 years) with non-insulin-dependent diabetes mellitus (NIDDM). The control group was similarly aged (mean age: 60.4 years, age range: 38-81). The levels of t-PA and t-PA/PAI-1 ratio of the diabetic group (mean +/- SD; 9.8 +/- 4.3 ng/ml, 0.94 +/- 0.47, respectively) were significantly higher than that of the control group (5.5 +/- 2.5 ng/ml, 0.51 +/- 0.23, respectively). The increased levels of t-PA antigen and t-PA/PAI-1 ratio in diabetics mean that free t-PA has been released. However, there was no significant difference in the level of PAI-1 between the diabetic group (12.9 +/- 6.4 ng/ml) and the control group (12.1 +/- 5.6 ng/ml). Levels of fibrinogen, plasminogen and alpha 2 PI in plasma were not different in the two groups. Duration of the disease, levels of glycosylated hemoglobin, differences in treatment and presense of diabetic nephropathy or retinopathy did not affect the fibrinolytic parameters. The levels of fibrinogen was higher in those with nephropathy than in the diabetics without nephropathy and retinopathy (p less than 0.05). There were no significant differences in the levels of t-PA, t-PA/PAI-1 ratio and PAI-1 between younger (less than 65 years) and older (65 years or more) subjects, in either the control or diabetic groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Tissue-type plasminogen activator and its inhibitor (PAI-1) in plasma in cases of non-insulin-dependent diabetes mellitus (NIDDM)]. 212 12

Hormonal regulation in the production of a plasminogen activator (PA) was studied in rat hepatocytes in primary culture. Insulin and epidermal growth factor had no effect on the hepatic PA activity. However, glucagon and epinephrine augmented the activity, whereas dexamethasone suppressed it by lowering the production of hepatic PA rather than by inducing plasmin inhibitors or a plasminogen activator inhibitor (PAI). Dibutyryl cAMP, an analogue of cAMP, also augmented hepatic PA activity. The augmented activity level was lowered by either H-8, cycloheximide, or actinomycin D, suggesting that A-kinase and protein biosynthesis are closely associated with the augmentation. Glucocorticoid and hormones that act to raise the intracellular cAMP level may participate in hepatic PA production by the liver.
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PMID:Hormonal regulation of plasminogen activator production by rat hepatocytes in primary culture. 238 27

Parameters of fibrinolysis, including euglobulin fibrinolytic activity, tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PA-inhibitor) activity, and plasmin-alpha 2-antiplasmin complex (PAP) were studied in 62 patients (35 women and 27 men; ages 53 +/- 16 years) with either insulin-dependent (IDDM) or noninsulin-dependent (NIDDM) diabetes mellitus. Compared to a control group of similar age (n = 57), the diabetic patients had a significantly lower mean euglobulin fibrinolytic activity (1.2 +/- 0.7 vs. 1.7 +/- 1.1 ng/ml, p less than 0.01) but significantly higher mean t-PA antigen (15.7 +/- 8.4 vs. 6.6 +/- 2.9 ng/ml, p less than 0.001) and PA-inhibitor activity (2.6 +/- 1.3 vs. 1.5 +/- 0.7 IU/ml, p less than 0.001) levels. Significant univariate correlations were observed between PA-inhibitor activity and age (r = 0.32, p less than 0.05), diastolic blood pressure (r = 0.42, p less than 0.01) and euglobulin fibrinolytic activity (r = -0.40, p less than 0.01). In multivariate analysis, only body mass index (positively) and euglobulin fibrinolytic activity (negatively) remained significantly related to PA-inhibitor activity in the total diabetic population as well as in the NIDDM group. The only parameter in the IDDM group significantly related to PA-inhibitor activity was diastolic blood pressure. These results suggest that PA-inhibitor plays a role in the regulation of fibrinolysis in diabetes patients and that factors like obesity and hypertension may be related to reduced fibrinolysis via PA-inhibitor levels.
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PMID:Tissue-type plasminogen activator antigen and plasminogen activator inhibitor in diabetes mellitus. 244 56

Plasminogen activator inhibitor-1 (PAI-1) is an important physiological inhibitor of fibrinolysis. It circulates in blood both in free active form and in inactive form complexed with tissue type plasminogen activator (t-PA). Control mechanisms for its synthesis and release from hepatocytes and endothelial cells are important in the pathogenesis of thrombosis. Possible risk factors for myocardial infarction include high insulin and PAI-1 levels, which correlate with one another in healthy subjects, and fibrinogen, which together with PAI-1, is an acute-phase reactant. We therefore studied the interrelationships between PAI-1, plasma insulin, and acute-phase proteins in 67 patients with angina pectoris. Plasma insulin correlated strongly (r = 0.59, p less than 0.001) with PAI activity, free PAI-1 antigen (r = 0.60, p less than 0.001), and total PAI-1 antigen (r = 0.58, p less than 0.001). The acute-phase proteins, fibrinogen and C-reactive protein, correlated significantly with t-PA antigen, total PAI-1 antigen, and PAI-1/t-PA complexes but not with PAI activity or free PAI-1. The results suggest that insulin stimulates synthesis and release of free PAI-1 (probably via hepatocytes as previously shown with cell culture) and that endothelial cell synthesis and release of t-PA, together with PAI-1, reflects a nonspecific acute-phase response to chronic vascular disease. Hyperinsulinemia found in patients with angina pectoris could play a role in the development of myocardial infarction via the induction of high plasma PAI-1 activity.
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PMID:Plasma plasminogen activator inhibitor-1 in angina pectoris. Influence of plasma insulin and acute-phase response. 247 Mar 43


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