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)

The present study was performed to investigate the acute effects of physiologically induced hyperinsulinemia on plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (t-PA) and triglycerides (TG). Forty-one male patients with chronic coronary heart disease (CHD) and moderate hypertriglyceridemia were studied for 3 h; 33 of them during an oral glucose tolerance test (OGTT), whereas eight patients served as controls, receiving water only. All subjects in the OGTT group were adequate responders to glucose administration, giving peak values of glucose (median 6.90 mmol l-1) and insulin (median 123 mU l-1) after 1 h. TG were unchanged throughout the test period in both groups. After 1 h PAI-1 activity and antigen decreased significantly more in the OGTT group than in the controls (median values: PAI-1 act 23-12 vs. 12-12 U ml-1; (p < 0.001). PAI-ag 45-35 vs. 18-16 ng ml-1 (p < 0.05)). t-PA increased more in the OGTT group (0.70-1.20 vs. 0.50-0.63 IU ml-1 (p = 0.08)). These differences tailored off after 3 h. We conclude that acute hyperinsulinemia, when generated during an OGTT, stimulates fibrinolysis with a consequent decrease in PAI-1 activity, but give no change in TG. The postulated regulating role of insulin for the steady state levels of PAI-1 could probably not be elucidated in the present dynamic model.
 ...
PMID:Insulin and PAI-1 levels during oral glucose tolerance test in patients with coronary heart disease. 803 49

ABA block copolymers of polyethylene glycol and poly-DL-lactic acid were prepared by ring-opening polymerization of DL-dilactide with alpha,omega-dihydroxy polyethylene glycol, Mn 1000 or 2000. The morphology of the resulting copolymers, with PEG:PLA ratios(mol/mol) of 1:2, 1:3 and 1:4, was characterized by DSC and ESR spectroscopy. The rate of water uptake was biphasic, reflecting the contribution of two processes: rapid diffusion of water into the initially miscible PEG and PLA blocks; then a slower rate of hydration possibly due to phase separation and hydrolytic cleavage of the PLA blocks. The rate of hydrolytic degradation of the block copolymers in DI water at 37 degrees C was measured by two methods: weight loss and colorimetric analysis of the carboxy end group concentration resulting from chain scission of PLA blocks. As a result of phase separation, the rate of scission of PLA blocks in the copolymers was similar to that of the PLA homopolymer. The more rapid onset of weight loss of the copolymers, relative to PLA, is attributed to the greater water solubility of PEG-PLA oligomers and their greater diffusivity in the more highly hydrated copolymers.
 ...
PMID:Poly-DL-lactic acid: polyethylene glycol block copolymers. The influence of polyethylene glycol on the degradation of poly-DL-lactic acid. 803 37

Purified tetanus toxoid, a high-molecular-weight protein, was entrapped within poly(L-lactic acid) (PLA) and poly(D,L-lactic/glycolic acid) (PLGA) microspheres prepared by either a solvent extraction or a solvent evaporation method carried out in a multiple emulsion system (water-in-oil-in-water). The physical integrity and antigenicity of the protein treated under different processing conditions were investigated. A reduction of antigenicity that was related to the percentage of aggregated protein was noticed under some experimental conditions. This partial loss of antigenicity was associated with the lyophilization process and affected by the nature of the organic solvent. All types of microspheres prepared with different molecular weight PLA and PLGA displayed a high protein-loading efficiency (> 80%) but their size was strongly influenced by polymer molecular weight (3000 versus 100,000). Protein release pattern was influenced by both polymer molecular weight and composition (PLA versus PLGA). A constant release pattern after an induction period of 10 days was observed for microspheres composed of high-molecular-weight polymers (PLA and PLGA). The release rate was lower from PLA microspheres than from PLGA microspheres. In contrast, a continuously increasing release rate preceded by a burst was observed for low-molecular-weight (3000) PLGA microspheres. Microencapsulated tetanus toxoid was significantly more immunogenic in mice than fluid toxoid as determined by IgG anti-tetanus antibody levels and neutralizing antibodies. However, the magnitude and duration of the antibody response did not differ significantly from a similar dose of aluminium phosphate-adsorbed toxoid. We conclude that microencapsulated tetanus toxoid shows significant adjuvant activity.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Biodegradable microspheres as controlled-release tetanus toxoid delivery systems. 817 50

Safety and efficacy of the thrombolytic agent urokinase (URO) in the elimination of subarachnoid clot and prevention of chronic vasospasm was compared with tissue-type plasminogen activator (rt-PA) in a blind, randomized placebo-controlled trial. Twenty monkeys were randomly assigned to one of five groups of four. Each group underwent baseline cerebral angiography followed by bilateral craniectomy and experimental subarachnoid hemorrhage. An Ommaya reservoir was inserted on the right side with its catheter placed into the ipsilateral subarachnoid space. Twenty-four hours later, depending upon group assignment, the animals received 100,000 IU URO, 200,000 IU URO, 1 mg rt-PA, 2 mg rt-PA, or the equivalent volume of normal saline (control group). On Day 7, angiography was repeated and the animals were killed. One animal died as a result of complications during the baseline angiography, presumably due to blood loss and prolonged anesthesia, and a replacement animal was obtained. No animals demonstrated any delayed neurological deficits. The study demonstrated that a single intracisternal bolus injection of rt-PA, 2.0 mg in 2 ml sterile water, or URO, 200,000 IU in 2 ml sterile water, 24 hours after induction of experimental subarachnoid hemorrhage in primates, was equally effective in thrombolysing ipsilateral clot, but neither dosage prevented angiographic vasospasm. Vasospasm occurred bilaterally in all groups. Whereas gross subarachnoid clot was found bilaterally in all animals in the placebo group and both smaller-dose URO and rt-PA groups, right-sided subarachnoid clot was virtually absent and left-sided clot reduced in both higher-dose URO and rt-PA groups.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Comparison of intrathecal administration of urokinase and tissue plasminogen activator on subarachnoid clot and chronic vasospasm in a primate model. 823 10

Controlled-release formulations based on poly(lactic) (PLA) and poly(lactic/glycolic) acid (PLGA) microspheres containing tetanus vaccine were designed. The polymers forming the microspheres were L-PLA of different molecular weights and DL-PLGA, 50:50. These microspheres were prepared by two solvent elimination procedures, both using a double emulsion, and were characterized for size, morphology, and toxoid release kinetics. The influence of formulation variables such as polymer type, vaccine composition, and vaccine/polymer ratio was also investigated. Both techniques yielded microspheres with similar size, morphology, and release properties. Microsphere size was dependent on the type of polymer and the presence of the surfactant L-alpha-phosphatidylcholine, which led to a reduction in microsphere size. On the other hand, the release kinetics of encapsulated protein were affected by the polymer properties (ratio lactic/glycolic acid and molecular weight) as well as by the vaccine composition, vaccine loading, and microsphere size. Moreover, for some formulations, a decrease in microsphere size occurred simultaneously, with an increase in porosity leading to an augmentation of release rate. The changes in the PLA molecular weight during in vitro release studies indicated that release profiles of tetanus toxoid from these microspheres were only marginally influenced by polymer degradation. A significant fraction of protein (between 15 and 35%) was initially released by diffusion through water-filled channels. In contrast, the decrease in the PLGA molecular weight over the first 10 days of incubation suggested that erosion of the polymer matrix substantially affects protein release from these microspheres. Among all formulations developed, two differing in microsphere size, polymer hydrophobicity, and release profile were selected for in vivo administration to mice.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Determinants of release rate of tetanus vaccine from polyester microspheres. 837 56

We have characterized the effects of ultrasound on fibrinolysis in vitro to investigate the mechanism of ultrasonic potentiation of fibrinolysis and to identify potentially useful ultrasound parameters for therapeutic application. Radiolabeled clots in thin walled tubes were exposed to ultrasound fields in a water bath at 37 degrees C, and lysis was measured by solubilization of radiolabel. Ultrasound accelerated lysis of plasma, whole blood, and purified fibrin clots mediated by recombinant tissue-type plasminogen activator (rt-PA), urokinase, or streptokinase, but ultrasound by itself caused no clot solubilization. The degree of ultrasonic potentiation was dependent on plasminogen activator concentration, increasing from 2.2-fold at a streptokinase concentration of 75 U/mL to 5.5-fold at 250 U/mL in a 1 MHz ultrasound field at 4 W/cm2. Ultrasound exposure resulted in heating due to absorption by the plastic tube, but the temperature increase was insufficient to account for the increase in clot lysis rate, indicating that the primary effect was nonthermal. Ultrasound did not accelerate hydrolysis of a peptide substrate by rt-PA and did not alter the rate of plasmic degradation of fibrinogen, indicating that the augmentation of enzymatic fibrinolysis required the presence of a fibrin gel. The acceleration of fibrinolysis by ultrasound was greater at higher intensities and duty cycles and was maximum at frequencies between 1 and 2.2 MHz, but decreased at 3.4 MHz. These findings suggest that ultrasound accelerates enzymatic fibrinolysis by increasing transport of reactants through a cavitation-related mechanism.
 ...
PMID:Characterization of ultrasound-potentiated fibrinolysis in vitro. 849 Jan 72

In order to obtain selective suicide substrates of trypsin-like proteases including plasminogen activators, plasmin, and thrombin, a series of cyclopeptides cyclo[Arg or Lys-aB(CH2X)-Gly4], in which a substituted o- or m-aminobenzoyl group constitutes a latent electrophile, have been prepared. Treatment of the corresponding phenyl ethers cyclo[P1-aB(CH2OC6H5)-Gly4] with HBr/HOAc or R1R2S/TFA gives the bromides (X = Br) or the sulfonium salts (X = +SR1R2 with R1 = R2 = Me or R1 = Me and R2 = C6H5), respectively. These water-soluble cyclopeptides behave as time-dependent inhibitors of bovine trypsin and human urokinase (u-PA) but have no effect on tissue plasminogen activator (t-PA) and no or poor effect on plasmin and thrombin. The compounds containing a m-aminobenzoic acid residue are more efficient inactivators than their anthranilic analogues. The kinetic criteria expected for a suicide inhibition are met. A mechanism of inhibition involving the formation of a quinonimmonium methide intermediate is proposed. The activity of the inhibitors is very sensitive to the nature of the X benzylic substituent. An increased efficiency for the inactivation of human urokinase is observed with the sulfonium salts. The selectivity of the inactivation of u-PA compared to t-PA could be of therapeutical significance in controlling cell proliferation and invasion.
 ...
PMID:New mechanism-based inactivators of trypsin-like proteinases. Selective inactivation of urokinase by functionalized cyclopeptides incorporating a sulfoniomethyl-substituted m-aminobenzoic acid residue. 849 23

We have previously shown that humic acid (well-water humic acid, HA, and synthetic humic acid, SHA) enhances cell surface expression of tissue factor (TF). Here we report that incubation of human umbilical vein endothelial cells (HUVEC) for 2 hr with HA or SHA cause a rapid rise in TF mRNA levels, as shown by Northern blot analysis. To understand the cytotoxic and fibrinolytic effects of HA and SHA on cultured HUVEC, the cells treated with varying concentrations of HA and SHA for various periods of time. Both HA and SHA (10-200 micrograms/ml) inhibited the viability of subconfluent HUVEC, cultured in the presence or absence of 20% FBS (Fetal Bovine serum) in the culture medium, in a dose-dependent manner. Both HA and SHA induced surface changes in the HUVEC as revealed by scanning electron micrography (SEM). However, protocatechuic acid, the monomer of SHA, did not significantly inhibit cell growth, and showed a cytotoxic effect only at 200 micrograms/ml. Furthermore both HA and SHA stimulated HUVEC to produce plasminogen activator inhibitor (PAI-1) and tissue plasminogen activator (t-PA) in a dose and time dependent fashion; the amount of PAI-1 produced was found to exceed that of t-PA. The monomer of SHA did not have this stimulatory effect. These results distinctly suggest that in addition to the inhibition of viability HA is involved in TF induction and PAI-1 synthesis in HUVEC and these may be some of the plausible mechanisms underlying the thrombotic disorders in Blackfoot disease.
 ...
PMID:Effects of humic acid on the viability and coagulant properties of human umbilical vein endothelial cells. 861

The hypothesis that tea drinking may protect against coronary heart disease (CHD) through effects on clotting as measured by plasma fibrinogen, tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) was tested in 65 healthy volunteers (31 men and 34 women; aged 20-74 years) in a randomized, blind, placebo-controlled, crossover study lasting 10 weeks (run-in phase 2 weeks, tea and placebo phases 4 weeks). During the placebo phase, intakes of milk, sugar, water and caffeine were matched to those in the tea phase during which 6 mugs of tea were drunk daily. Compliance with tea intake was measured by marking tea bags with p-aminobenzoic acid and measuring recovery in 24-hour urine collections. The mean +/- SD fibrinogen level, PAI-1 activity and tPA antigen level at baseline of 2.91 +/- 0.81 g/l, 7.9 +/- 5.3 U/ml and 4.76 +/- 2.17 ng/ml, respectively, were in the normal range. No significant differences in these variables between the run-in, tea or placebo phases were observed. The putative protective effect of tea against development of CHD is not mediated through effects of black tea on fibrinogen, tPA or PAI-1.
 ...
PMID:Tea drinking and haemostasis: a randomized, placebo-controlled, crossover study in free-living subjects. 869 79

The design of biodegradable microparticle drug delivery systems with precisely tailored surface properties requires surface analytical methods that can relate polymer chemistry and fabrication parameters to the final surface chemistry of the microparticles. We demonstrate using X-ray photoelectron spectroscopy (XPS) that it is possible to identify significant variations in the surface chemistry of microparticles composed of poly(lactic acid) (PLA), poly(lactide-co-glycolide) (PLGA), or block copolymers of PLA or PLGA with poly(ethylene glycol) (PEG). These variations are related to the mechanism by which the microparticle/water interface is stabilized. This, in turn, is controlled by the interfacial surface tensions of the polymers within aqueous environments. For PEG containing block copolymers, adsorption of a surfactant, poly(vinyl alcohol) (PVA), from the aqueous medium onto the polymer is reduced compared with the PLA and PLGA polymers. This reduction is achieved because the PEG segments, within the copolymer structure, stabilize the polymer/water interface. Estimates of the relative amounts of lactide, lactide-co-glycolide, vinyl alcohol, and ethylene glycol monomer units at the microparticle surfaces are presented based on curve-fitting analysis of the XPS data.
 ...
PMID:The Adsorption of Poly(vinyl alcohol) to Biodegradable Microparticles Studied by X-Ray Photoelectron Spectroscopy (XPS) 902 8


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>