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)

Poly-L-lysine and certain mixed polymers of L-lysine and other amino acids modify the activity of one- and two-chain tissue-type plasminogen activator (t-PA) towards its substrates. In particular the rate of plasminogen activation in the presence of optimal poly-L-lysine concentrations, is increased by approximately 100-fold. In contrast, activity towards a small synthetic substrate is inhibited by 85%. These effects are observed with both the one- and two-chain forms of t-PA. The use of poly-L-lysines in a coupled assay system optimised for t-PA and plasmin activities allows the reproducible assay of t-PA at the 10(-12) to 10(-13) molar level.
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PMID:Poly-lysines as modifiers of one- and two-chain tissue-type plasminogen activator activity. 309 22

Poly(dl-lactide) (PLA) microspheres containing quinidine or quinidine sulphate were prepared by the emulsification-solvent evaporation technique. The in vitro release profile of quinidine or quinidine sulphate from the microspheres was characterized by three phases: a lag time, a rapid release phase (burst), and a slow release phase. Drug release was studied as a function of the ionic strength of the dissolution medium, to demonstrate the importance of the water imbition into the microspheres which induced the drug release. The lag time increased with increasing ionic strength. The microspheres stayed intact during the dissolution study as shown by scanning electron microscopy (SEM). Disintegration of microspheres which was initially observed was an artifact introduced during the SEM procedure. The high vacuum applied either during the coating of the microspheres with gold-palladium or during the actual observation in the scanning electron microscope caused the microspheres to collapse or rupture.
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PMID:Polylactic acid microspheres containing quinidine base and quinidine sulphate prepared by the solvent evaporation method. III. Morphology of the microspheres during dissolution studies. 323 52

Poly(A)+-RNA from human kidney and human embryonal lung fibroblasts fractionated by sucrose gradient centrifugation was translated in Xenopus oocytes. Assay for plasminogen-dependent fibrinolytic activity detected synthesis of secreted plasminogen activator and revealed the active fraction of poly(A)+-RNA with a sedimentation coefficient of approximately 23S. Translation products of the active fraction were immunoadsorbed by antiurokinase monoclonal antibodies immobilized on sepharose. Gel electrophoretic analysis of the protein products showed that the 23S fraction of poly(A)+-RNA from human kidney contains mRNA for single-chain urokinase-type plasminogen activator with apparent molecular weight of approximately 50 kDa.
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PMID:[mRNA for the plasminogen activator of the urokinase type: translation in oocytes of Xenopus laevis]. 339 55

Induction of synthesis of the protease plasminogen activator (PA) by hormones, oncogenic viruses and tumor promoters occurs at the transcription level. A novel bioassay for PA messenger RNA was developed to study the regulation of PA synthesis and the genetic elements involved in it. Poly(A)-containing RNA from HEp-3, a PA-rich tumor of human origin, was found to direct the synthesis of a new proteolytic activity when microinjected into Xenopus oocytes. Newly synthesized protease can be detected within a few hours after microinjection of minute quantities of unfractionated mRNA. The new enzymatic activity is indistinguishable from human PA: it is absolutely dependent on human plasminogen; it is neutralized by serum raised against urokinase, the human urinary PA; and it comigrates with urokinase and HEp-3 PA in gel electrophoresis, exhibiting a molecular weight of 60,000.
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PMID:Microinjected Xenopus oocytes synthesize active human plasminogen activator. 616 5

The activity of primaquine (PQ) was compared to that of PQ-loaded Poly (D,L-Lactide) (PLA) nanoparticles against Leishmania donovani. The association of PQ with PLA nanoparticles increased the antileishmanial in vitro and in vivo effects of intravenously administered drug while its toxicity was reduced. The effectiveness of PQ-loaded PLA nanoparticles was 3.3 times as high as that of free drug in the suppression of amastigotes in the liver of BALB/c mice. A total dose of 30 mg PQ bound/kg (600 mg PLA/kg) was well tolerated and no sign of acute toxicity was observed. A similar dose of free drug resulted in 15% weight loss. No significant leishmanicidal activity was observed for unloaded PLA nanoparticles. Ultrastructural studies showed the uptake of drug-loaded nanoparticles by Leishmania-infected Kupffer cells. Nanoparticles were identified closed to amastigotes.
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PMID:The activity and ultrastructural localization of primaquine-loaded poly (d,l-lactide) nanoparticles in Leishmania donovani infected mice. 789 92

Poly(D,L-lactide) (DL-PLA) and poly(D,L-lactide-co-glycolide) (DL-PLGA) microspheres containing a non-steroidal anti-inflammatory model drug, piroxicam, were prepared by a spray drying process. The microspheres were characterized for surface morphology by scanning electron microscopy, particle size distribution by laser diffraction spectrometry, drug content and in vitro drug release. The diameters of the microspheres ranged from 1 to 15 microns. The DL-PLA particles appeared to be more spherical and smooth than the DL-PLGA particles, which showed a more undulated surface. Piroxicam content in the microspheres was 10%. A very high encapsulation efficiency of 99.0% was achieved with both polymers. In vitro release studies were carried out in a flow-through cell. The in vitro release rate of the drug from the DL-PLA microspheres was very slow. Less than 20% of the loaded drug was released within 10 d. The release mechanism was diffusion controlled and followed a square root of time relationship. Only a very small initial burst effect was observed. In contrast, the DL-PLGA microspheres provided a much faster drug release: about 50% was released within the first 5 h of the experiment. The mechanism for piroxicam release from the DL-PLA microspheres is not matrix erosion, but mainly drug diffusion through the intact polymer barrier. For the DL-PLGA microspheres, a pore diffusion release mechanism is proposed.
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PMID:Piroxicam release from spray-dried biodegradable microspheres. 816 57

Poly-(lactide-co-glycolide) microspheres with entrapped antigen have shown considerable promise as controlled release vaccines. To enhance the immunomodulatory effect of LW 50020, a bacterial lysate of seven common respiratory pathogens used perorally as an immunomodulator, we prepared poly-(D,L-lactide-co-glycolide) (PLG) and poly-(L-lactic acid) (PLA) microspheres with entrapped immunomodulator by solvent evaporation or solvent extraction double emulsion techniques. Physical properties, such as particle size, LW 50020 entrapment rate, antigen release patterns and morphological characteristics were investigated. All preparations displayed a high degree of antigen loading up to 95%, whereas size, surface morphology and antigen release patterns were significantly influenced by the method of preparation and the polymer components used. Solvent evaporation microspheres are porous particles from 0.8 micron to 2.0 microns in diameter, that show a rapid antigen release for PLG, and a moderate antigen release for PLA microspheres within 33 days. Solvent extraction microspheres have proven to be particles from 1.1 microns to 5.0 microns in diameter showing a smooth surface and a medium antigen release rate over 33 days. SDS-PAGE and immunoblotting of extracted antigen confirmed that the molecular weight and antigenicity of the immunomodulator remained unaltered by the entrapment procedure.
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PMID:Preparation and characterization of poly-(D,L-lactide-co-glycolide) and poly-(L-lactic acid) microspheres with entrapped pneumotropic bacterial antigens. 869 19

Tyrosine-derived polycarbonates are a new class of degradable polymers developed for orthopedic applications. In this study the long-term (48 week) in vivo degradation kinetics and host bone response to poly(DTE carbonate) and poly(DTH carbonate) were investigated using a canine bone chamber model. Poly(L-lactic acid) (PLA) served as a control material. Two chambers of each test material were retrieved at 6-, 12-, 24-, and 48-week time points. Tyrosine-derived polycarbonates were found to exhibit degradation kinetics comparable to PLA. Each test material lost approximately 50% of its initial molecular weight (Mw) over the 48-week test period. Poly(DTE carbonate) and poly(DTH carbonate) test chambers were characterized by sustained bone ingrowth throughout the 48 weeks. In contrast, bone ingrowth into the PLA chambers peaked at 24 weeks and dropped by half at the 48-week time point. A fibrous tissue layer was found surrounding the PLA implants at all time points. This fibrous tissue layer was notably absent at the interface between bone and the tyrosine-derived polycarbonates. Histologic sections revealed intimate contact between bone and tyrosine-derived polycarbonates. From a degradation-biocompatibility perspective, the tyrosine-derived polycarbonates appear to be comparable, if not superior, to PLA in this canine bone chamber model.
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PMID:Canine bone response to tyrosine-derived polycarbonates and poly(L-lactic acid). 873 Nov 47

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 have studied the release of nerve growth factor (NGF), a protein under consideration for treatment of Alzheimer's Disease, from polymer matrices and microspheres to characterize the stability of NGF, the dynamics of NGF release, and the distribution of NGF within the brain interstitium. Poly(ethylene-co-vinyl acetate) (EVAc) disks and poly(L-lactic acid) (PLA) microspheres were formed by codispersing NGF with one of a variety of molecules. The mass of mouse NGF (mNGF) detected following release from EVAc disks into buffered saline varied five-fold over the range of codispersants studied, with carboxymethyldextran providing optimal release, while the mass of recombinant human NGF (rhNGF) released varied four-fold from both EVAc disks and PLA microspheres, with albumin and carboxymethyldextran providing optimal release. Variation of the codispersant species significantly affected NGF release into buffered saline; it also had a noticeable, but small, effect of the amount of NGF found in the brain tissue following implantation of a polymer device. To improve NGF retention in tissue, NGF was conjugated to 70,000 molecular weight dextran and incorporated into a polymeric device. The distribution of NGF was enhanced by conjugation; comparison of NGF concentrations in the brain to a mathematical model of diffusion and elimination suggested that the elimination rate of NGF-dextran conjugate in the tissue was over seven times slower than the elimination rate of NGF. These results indicate that variation of the properties of the controlled release system may be useful in regulating the time course of NGF delivery to tissue, and that modification of the NGF itself can improve penetration and retention in the brain.
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PMID:Stabilization of nerve growth factor in controlled release polymers and in tissue. 895 7


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