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)

Staphylokinase, a fibrin-specific plasminogen activator, was highly expressed in Escherichia coli and purified by ion-exchange and gel-filtration chromatography. The purified recombinant staphylokinase was fully active and readily crystallized against 1.2 M sodium citrate in 100 mM Tris-HCl buffer at pH 8.0 using the hanging-drop method. Crystals of staphylokinase diffract to better than 2.2 A resolution. The crystal belongs to the tetragonal space group P4(1)2(1)2 or its enantiomorph with unit-cell parameters a = b = 67.5, c = 150.1 A. There are two molecules in the asymmetric unit. In this paper, we described the first crystallization of a kind of plasminogen activator and present the results of preliminary X-ray diffraction data from the native protein.
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PMID:Crystallization and preliminary X-ray diffraction studies of recombinant staphylokinase. 1529 79

The aim of this work was to investigate the role of HLB of emulsifier as well as volume of the internal aqueous phase (W(1)) and presence of salt in the external aqueous phase (W(2)) on the morphology, size and encapsulation efficiency of poly(D,L-lactide) microspheres containing naltrexone HCl. PLA microparticles containing naltrexone HCl, an effective opiate antagonist, were prepared by a water-in-oil-in-water emulsification-solvent evaporation procedure. One of the five different emulsifiers: span 80, span 20, tween 85, tween 80 and tween 20, with HLB values from 4-17 were added to W(1). Presence of emulsifier in W(1) resulted in smaller particles with a more dense and uniform internal structure. Incorporation of span 80 (HLB 4.3, suitable for W/O emulsions) yield the highest encapsulation efficiency. Increasing the HLB value to 8 or 11 (span 20 or tween 85) decreased the efficiency of naltrexone HCl-loading. HLB values higher than 15 (tween 80 or tween 20) increased encapsulation efficiency unexpectedly, which could be attributed to migration of these emulsifiers to the O/W(2) interface and modifying the surface properties of microparticles. Increasing the internal water phase volume from 0.2-1.8 ml resulted in larger particle size with poor encapsulation efficiency. Addition of 10% w/w NaCl to the W(2) changed the surface morphology of microspheres from a porous form to a smooth surface. It was shown that, by selecting the appropriate HLB value of emulsifier in W(1), addition of salt to W(2) and controlling the volume of W(1), one can control the encapsulation efficiency, size and morphology of microspheres.
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PMID:Effect of surfactant HLB and different formulation variables on the properties of poly-D,L-lactide microspheres of naltrexone prepared by double emulsion technique. 1601

With the aim to improve the fibrinolytic properties of carbons by different biological and electrochemical treatments, we modified graphite surfaces by fibrinogen adsorption and subsequent application of various constant potentials before submitting them to plasminogen adsorption. First, we verified that plasminogen (purified or present in human plasma) could adsorb onto these modified surfaces and that adsorbed plasminogen could be converted by t-PA (the principal physiological activator of plasminogen) to adsorbed plasmin. The catalytic properties of the generated enzyme were characterized in assay solutions containing t-PA, fibrinogen and the chromogenic substrate S-2403 (pyroGlu-Phe-Lys-p-nitroaniline, HCl). Experiments showed that the application of electrical potentials to the fibrinogen coating could indirectly affect the properties of the material. In the case of anodic potentials, the amidolytic activity of the generated plasmin was significantly enhanced. Especially, this activity was 10 times higher at a particular potential value.
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PMID:Electrochemical processing of fibrinogen modified-graphite surfaces: effect on plasmin generation from adsorbed plasminogen. 1602 86

Nanoparticle preparation by the emulsification-solvent evaporation method is a complex phenomenon. Various formulation factors can affect the internal structure and release of drug from nanoparticles (NPs). The aim of the present study is to optimize NPs of PEG-g-PLA polymer and study the effect of various factors on the porosity as well as release profile of drug-loaded NPs. Propafenone hydrochloride (Prop.HCl), a model drug, was encapsulated in NPs using different amounts of triethylamine (TEA) and initial drug loading levels. NPs were also prepared without TEA by using propafenone base (Prop). All the formulations were characterized for surface morphology, size and size distribution, encapsulation efficiency, thermal analysis, porosimetry and in vitro release studies. Encapsulation efficiency of Prop ranged between 10% and 43% and was dependent on initial drug loading as well as amount of TEA added. Porosity studies revealed different pore size distribution (PSD) for formulations with and without TEA. Formulations with higher drug loading showed greater volume contribution of small pores, higher fractal dimension suggesting more complex pore structure and slower drug release, probably due to decrease in the effective diffusion coefficient of Prop. Results suggest that formulation factors play an important role affecting the porosity and release rate of NPs. Also, fractal dimension could be one of the most important factors in determining the release behavior of NPs.
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PMID:Effect of porosity on the release kinetics of propafenone-loaded PEG-g-PLA nanoparticles. 1609 25

Poly(lactic acid) (PLA)-supported dibenzoylmethane (dbm) and corresponding metal complexes have potential applications as biomaterials and catalysts. Using hydroxyl-functionalized dbm (i.e., dbmOH) as the initiator and Sn(oct)2 as the catalyst, lactide ring-opening polymerizations were unexpectedly slow (6 h), and PDIs broadened when molecular weights >10 000 were targeted. Because interactions between the dbm ligand and Sn(oct)2 may be responsible for the diminished catalyst activity and molecular weight control, iron(III) was employed as a protecting group to form Fe(dbmOH)3. Shorter reaction times (10 min) were noted with this trifunctional metalloinitiator and Sn(oct)2, and higher molecular weights were achievable. Moreover, it was discovered that Fe(dbmOH)3 serves not only as an initiator but also as a catalyst and activating group for the polymerization. Even without the tin catalyst, iron-centered polymers with low PDIs (<1.1) were obtained within 10 min ( approximately 70% monomer conversion). The resulting Fe(dbmPLA)3 stars were demetalated by acid treatment to generate dbmPLA for subsequent coordination to other metals. To explore the scope of iron beta-diketonate complexes as catalysts, additional studies were performed with dbmOH and benzyl alcohol initiators using either iron tris(dbm) or iron tris(acac) (acac = acetylacetonate) as the catalyst. Here too, PLA products were obtained, and the iron catalysts were readily separated by treatment with aqueous HCl.
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PMID:Iron tris(dibenzoylmethane)-centered polylactide stars: multiple roles for the metal complex in lactide ring-opening polymerization. 1624 97

Recombinant human tissue-type plasminogen activator derivative (r-PA), fused with thioredoxin (Trx), was expressed in Escherichia coli. The resultant fusion protein, Trx-r-PA, was almost completely in the form of inclusion bodies and without activity. Different refolding strategies were investigated including different post-treatment of solubilized Trx-r-PA inclusion bodies, on-column refolding by size-exclusion chromatography (SEC) using three gel types (Sephacryl S-200, S-300 and S-400), refolding by Sephacryl S-200 with a urea gradient and two-stage temperature control in refolding. An optimized on-column refolding process for Trx-r-PA inclusion bodies was established. The collected Trx-r-PA inclusion bodies were dissolved in 6 M: guanidine hydrochloride (Gdm.HCl), and the denatured protein was separated from dithiothreitol (DTT) and Gdm.HCl with a G25 column and simultaneously dissolved in 8 M: urea containing oxidized glutathione (GSSG). Finally a refolding of Trx-r-PA protein on Sephacryl S-200 column with a decreasing urea gradient combined with two-stage temperature control was employed, and the activity recovery of refolded protein was increased from 3.6 to 13.8% in comparison with the usual dilution refolding.
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PMID:A comparative investigation on different refolding strategies of recombinant human tissue-type plasminogen activator derivative. 1661 26

The main objective of the present study was to evaluate the reduction in halofantrine (Hf) toxicity, an antimalarial drug frequently associated with QT interval prolongation in electrocardiogram, by its entrapment in poly-epsilon-caprolactone nanocapsules (NC). The acute lethal dose (LD(100)) of Hf.HCl experimentally observed was 200 mg/kg whereas the calculated LD(50) was 154 mg/kg. In contrast, the LD(100) for Hf-NC was 300 mg/kg with a longer mean time to death than Hf.HCl. The calculated LD(50) was 249 mg/kg for Hf-NC. The Hf entrapped in PCL NC presented a greater efficacy than PLA-PEG NC and than Hf solution in P. berghei-infected mice at 1 mg/kg. The cardiovascular parameters, ECG and arterial blood pressure, were evaluated in anaesthetized Wistar rats after the IV administration of a single, especially high dose (100 and 150 mg/kg) of halofantrine base loaded-nanocapsules (Hf-NC) or halofantrine chlorhydrate (Hf.HCl) solution. It was observed that Hf solution caused prolongation of the QT and PR intervals of the ECG; however, this effect was significantly (P<0.001) reduced when Hf was administered entrapped in nanocapsules. The treatment with Hf.HCl induced a pronounced bradycardia and severe hypotension leading to death. The effect of Hf-NC upon heart rate was reduced from 58 to 75% for 100 and 150 mg/kg, respectively, when compared with Hf.HCl solution. These findings show that the encapsulation of halofantrine reduces the QT interval prolongation of ECG in rats and suggest that a modification of drug distribution was possible by using nanocapsules. Hf encapsulation was the main factor responsible for the significant reduction in cardiac toxicity observed.
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PMID:Cardiotoxicity reduction induced by halofantrine entrapped in nanocapsule devices. 1730 79

In this study, the authors report the purification and characterization of antitoxic proteins from the serum of Agkistrodon halys Pallas. Two antitoxic proteins have been successfully isolated by the methods of (NH4)(2)SO(4) fractional precipitation, chromatography and preparative discontinuous polyacrylamide gel electrophoresis (PAGE). We have measured their molecular weights by Sephadex G-150 chromatography and 0.1% SDS-Tris-HCl discontinue PAGE respectively. Antitoxin I was about 138,000+/-40 Da and antitoxin II was about 76,000+/-40 Da, they are all single-chain peptides. We have measured their capacity to neutralize the toxicity of agkistrodotoxin (ATX), and their capacity to inhibit the PLA(2) activity of ATX. The results showed that antitoxin I could increase LD(50) of ATX from 0.25+/-0.05 to 0.445+/-0.13 mg/kg, decrease its PLA(2) activity from 2.36 to 1.72 microm/mg min, and antitoxin II could increase LD(50) of ATX from 0.25+/-0.05 to 0.56+/-0.12 mg/kg, decrease Phospholipase A(2) (PLA(2)) activity from 2.36 to 1.2 microm/mg min. When the natural antitoxins were mixed with different amounts of ATX and inoculated intraperitonially into eight mice, it was found that 0.5 mg antitoxin I could neutralize the toxicity of 0.4 mg ATX and 0.5 mg antitoxin II could neutralize the toxicity of 0.5 mg ATX completely. These antitoxic proteins could neutralize the toxicity of ATX completely and inhibit ATX's PLA(2) activity partially.
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PMID:Purification and characterization of antitoxic proteins from the serum of Agkistrodon halys Pallas. 1751 68

Schizophrenia may reflect a sensitization of dopaminergic (DA) function. Apomorphine (Apo), a DA receptor agonist, induces both sensitization and tolerance of DA function in rodents depending on dose intervals. We investigated sensitization and tolerance to Apo in healthy male volunteers. After a period of acclimatization to the experimental setting (Day 1) subjects were assigned randomly to two groups: Group A subjects received seven injections of placebo (physiological saline) (PLA) and Group B subjects received seven injections of Apo HCl (7 microg/kg sc) under double-blind conditions at 2 h intervals commencing at 0930 hours (Day 2) after an overnight fast. Twelve hours after the seventh injection, i.e. on Day 3, after an overnight fast all subjects received an injection of Apo. Serial samples of blood commencing at 0900 hours were drawn after the first and last injection in both groups for assay of growth hormone (GH), prolactin (PRL) and cortisol by radioimmunoassay; sleepiness was measured using the Analog Sleepiness Rating Scale and yawning recorded by video recorder. The GH response in Group B (N = 8) was (a) decreased after the eighth injection of Apo compared with the first injection of Apo (P = 0.03) and (b) decreased after the eighth injection of Apo compared with the first injection of Apo in Group A (N = 10) (P = 0.001). The number of yawns in Group B was significantly decreased after the eighth injection of Apo compared with the first injection of Apo (P = 0.042). PRL, cortisol and sleepiness were not significantly different between the first and eighth injection of Apo. Sensitization was not observed in any of the measures studied. These results are compatible with induction of acute tolerance of DA-mediated GH and yawning responses. The method used provides a safe pharmacological paradigm to examine plasticity of DA mechanisms in man. Results are discussed in the context of possible therapeutic implications for schizophrenia.
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PMID:Induction of tolerance of dopaminergic responses in man. 1850 87

Nanofibrous blends of HCl-doped poly(aniline-co-3-aminobenzoic acid) (3ABAPANI) copolymer and poly(lactic acid) (PLA) were fabricated by electrospinning solutions of the polymers, in varying relative proportions, in dimethyl sulfoxide/tetrahydrofuran mixture. The morphology, mechanical and electrical properties of the nanofibers were characterized and an assessment of their bioactivity performed. To assess cell morphology and biocompatibility, pure PLA and 3ABAPANI-PLA nanofibrous mats were deposited in the form of three-dimensional networks with a high degree of connectivity, on glass substrates, and their ability to promote proliferation of COS-1 fibroblast cells was determined. The nanofibrous electrospun 3ABAPANI-PLA blends gave enhanced cell growth, potent antimicrobial capability against Staphylococcus aureus and electrical conductivity. This new class of nanofibrous blends can potentially be employed as tissue engineering scaffolds, and in particular have showed promise as the basis of a new generation of functional wound dressings that may eliminate deficiencies of currently available antimicrobial dressings.
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PMID:Electrospun functionalized polyaniline copolymer-based nanofibers with potential application in tissue engineering. 2084 83


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