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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hexadecafluoro zinc phthalocyanine (ZnPcF16), a second-generation sensitizer for the photodynamic therapy (PDT) of cancer, was formulated in polyethylene-glycol-coated poly(lactic acid) nanoparticles (PEG-coated PLA-NP) and tested in EMT-6 tumour-bearing mice for its photodynamic activity. The tumour response was compared to that induced by the same dye formulated as a Cremophor EL (CRM) emulsion. Formulation in the biodegradable NP improved PDT response of the tumour while providing prolonged tumour sensitivity towards PDT.
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PMID:Photodynamic therapy of tumours with hexadecafluoro zinc phthalocynine formulated in PEG-coated poly(lactic acid) nanoparticles. 864 56

A bioresorbable aliphatic polyester was synthesized by bulk copolymerization of a 1/1 M/M L,L-lactide/epsilon-caprolactone mixture using zinc metal as initiator. The actual composition of the copolymer was found to be 1.5/1 as deduced from 1H NMR spectra obtained in DMSO-d6 solutions where higher resolution was obtained as compared with chlorinated solvents. Resonances due to L-lactyl units (L) exhibited triads stereosensitivity, epsilon-oxycaproyl units (C) being sensitive to dyads. Average lengths of both poly(lactic acid) and polycaprolactone sequences were evaluated and showed the presence of rather long PLA blocks. Furthermore, no CLC triad signal was found, suggesting the absence of transesterification rearrangements. 10 x 10 x 2 mm specimens made of the copolymer were allowed to age in isoosmolar pH = 7.4 phosphate buffer at 37 degrees C. Degradation was monitored by various analytical techniques such as SEC, X-ray diffractometry, DSC, and 1H NMR. Data were compared with the behaviour of PCL and PLA homopolymers allowed to age under similar conditions. Crystallinity and composition changes are discussed in terms of preferential degradation in L- and C-containing amorphous domains, crystallized long PLA blocks being much more resistant.
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PMID:Structural characterization and hydrolytic degradation of a Zn metal initiated copolymer of L-lactide and epsilon-caprolactone. 899 92

Under the control of trp promoter, human tissue-type plasminogen activator was expressed in E. coli in the form of inclusion body. The recombinant t-PA was recovered for renaturation from preparative native PAGE, gel by zinc acetate staining and electroelution. After renaturation in vitro, the recombinant t-PA was purified by benzamidine affinity chromatography and lysine affinity chromatography. The purified t-PA showed homogeneous on silver-stained SDS-PAGE gel, with a specific activity of 240,000 I.U./mg protein.
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PMID:Renaturation and purification of recombinant tissue-type plasminogen activator expressed in E. coli. 911 42

The urokinase receptor (uPAR) binds urokinase-type plasminogen activator (u-PA) through specific interactions with uPAR domain 1, and vitronectin through interactions with a site within uPAR domains 2 and 3. These interactions promote the expression of cell surface plasminogen activator activity and cellular adhesion to vitronectin, respectively. High molecular weight kininogen (HK) also stimulates the expression of cell surface plasminogen activator activity through its ability to serve as an acquired receptor for prekallikrein, which, after its activation, may directly activate prourokinase. Here, we report that binding of the cleaved form of HK (HKa) to human umbilical vein endothelial cells (HUVEC) is mediated through zinc-dependent interactions with uPAR. These occur through a site within uPAR domains 2 and 3, since the binding of 125I-HKa to HUVEC is inhibited by vitronectin, anti-uPAR domain 2 and 3 antibodies and soluble, recombinant uPAR (suPAR), but not by antibody 7E3, which recognizes the beta chain of the endothelial cell vitronectin receptor (integrin alphavbeta3), or fibrinogen, another alphavbeta3 ligand. We also demonstrate the formation of a zinc-dependent complex between suPAR and HKa. Interactions of HKa with endothelial cell uPAR may underlie its ability to promote kallikrein-dependent cell surface plasmin generation, and also explain, in part, its antiadhesive properties.
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PMID:Binding of high molecular weight kininogen to human endothelial cells is mediated via a site within domains 2 and 3 of the urokinase receptor. 929 14

A kininogen binding protein(s), a putative receptor, was identified on endothelial cells. A 54-kDa protein was isolated by a biotin-high molecular mass kininogen (HK) affinity column that, on aminoterminal sequencing of tryptic digests, was identified as cytokeratin 1. Multiple antibodies directed to cytokeratin 1 reacted with a 54-kDa band on immunoblot of lysates of endothelial cells. On laser scanning confocal microscopy, cytokeratin 1 antigen was found on the surface of endothelial cells. Cytokeratin 1 antigen also was detected on endothelial cell membranes by flow cytometry. Moreover, an antipeptide antibody to a sequence unique to cytokeratin 1 also specifically bound to nonpermeabilized endothelial cells. Biotin-HK specifically bound to cytokeratin only in the presence of Zn2+, and cytokeratin blocked biotin-HK binding to endothelial cells. Further, HK and low molecular mass kininogen, but not factor XII, blocked biotin-HK binding to cytokeratin, and peptides of each cell binding region of HK on domains 3,4, and 5 blocked biotin-HK binding to cytokeratin. gC1qR and soluble urokinase-like plasminogen activator receptor also inhibited biotin-HK binding to cytokeratin. These investigations identify a new function for cytokeratin 1 as a kininogen binding protein. Cytokeratins, members of the family of intermediate filament proteins, may represent a new class of receptors.
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PMID:Identification of cytokeratin 1 as a binding protein and presentation receptor for kininogens on endothelial cells. 952 Apr 14

For more than two decades, it has been known that activation of the plasma kallikrein/kinin system only occurs when it is exposed to artificial, negatively charged surfaces. The existence of physiological, negatively charged surfaces has, however, never been demonstrated in vivo. In this report, we describe current knowledge about how the proteins of the plasma kallikrein/kinin system interact with and become activated on cell membranes. In this model, activation of the plasma kallikrein/kinin system on endothelial cells is not initiated by factor XII autoactivation, as seen on artificial surfaces. On endothelial cells, plasma prekallikrein is activated by a membrane-associated cysteine protease. This activation is dependent on the presence of high molecular weight kininogen and an optimal zinc (Zn2+) concentration. Although the initiation of activation of plasma prekallikrein is independent of factor XII, kallikrein-mediated factor XIIa generation, in turn, accelerates the activation of the system. Further kallikrein formed on endothelial cell membranes is capable of cleaving its receptor and native substrate, high molecular weight kininogen, liberating bradykinin and terminating activation. In addition, the kallikrein formed on the surface of endothelial cells results in kinetically favorable activation of prourokinase and, subsequently, plasminogen. Activation of the plasma kallikrein/kinin system on endothelial cells proceeds by a physiological mechanism to initiate cellular fibrinolysis independent of plasmin, fibrin, and tissue-type plasminogen activator.
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PMID:Activation of the plasma kallikrein/kinin system on endothelial cells. 1035 62

Nowadays, many degradable polymers are being used under the form of interference screws to fix the bone-tendon-bone autograft in anterior cruciate ligament reconstruction. However, little is known about the post-implantation fate of these screws, especially about the formation of crystalline residues which seems to be a critical factor for the success of surgery with temporary implants based on lactic and glycolic acid derived polymers (PLAGA). In an attempt to bring in some new insights, various high molecular weight stereoregular poly(lactide)s (PLAX with X = percentage of L-lactyl units) obtained by ring-opening polymerization of lactides in the presence of zinc-metal (PLA98-Zn), zinc lactate (PLA98-Znlac) or stannous octoate (PLA100-Sn), were processed by injection-molding to make interference screws to be compared. In vivo data were collected from screws implanted in sheep knees with follow ups ranging from 6 months to 5 years. Histology confirmed the heterogeneous degradation mechanism introduced nearly 10 years ago from in vitro investigations of homemade implants having simpler geometry. The effects of the initiator system (zinc- or tin derivatives) used to polymerize the lactide monomer on the properties of injection molded interference screws was also investigated in vitro in a phosphate buffer solution at 37 degrees C. Major differences in terms of hydrophilicity, hydrolysis rate and loss of mechanical properties were observed between PLA-Zinc and PLA-Tin. Discussion of the behavior of interference screws of different compositions was made on the basis of the present understanding of PLAGA morphology and degradation characteristics.
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PMID:In vitro and in vivo degradation of lactic acid-based interference screws used in cruciate ligament reconstruction. 1041 76

The zinc endopeptidases mutalysin I (100 kDa) and mutalysin II (22.5 kDa) have been previously isolated from bushmaster (Lachesis muta muta) snake venom. Hemorrhagic activity was observed with as little as 0.5 microg (2000 units/mg) and 17.8 microg (56.2 units/mg) for mutalysin I and II, respectively. Additionally, the proteases hydrolyse the Aalpha>Bbeta chain of fibrinogen without clot formation. The specific fibrinogenolytic activity was estimated as 5. 25 and 16.3 micromol fibrinogen/min/micromol protein for mutalysin I and II, respectively. In vitro, the enzymes act directly on fibrin and are not inhibited by serine proteinase inhibitors (SERPINS). Analysis by SDS-PAGE of fibrin hydrolysis by both enzymes showed that mutalysin II (0.22 microM) completely digested the alpha- and gamma-gamma chains and partially the beta-chain (in 120 min incubation). In contrast, mutalysin I (three fold higher concentration than mutalysin II) hydrolyzed selectively the alpha-chain of fibrin leaving the beta and gamma-gamma chains unaffected. Unlike with the plasminogen activator-based thrombolytic agents (e.g., streptokinase), mutalysins do not activate plasminogen. Neither enzyme had an effect on protein C activation. Mutalysin II does not inhibit platelet aggregation in human PRP induced by collagen or ADP. However, mutalysin I showed a selective inhibitory effect on collagen-induced aggregation of human PRP; it did not affect platelet aggregation with ADP as the agonist. The present investigation demonstrates that both native and EDTA-inactivated mutalysin I dose dependently blocked aggregation of human PRP elicited by 10 microg/mL of collagen with an IC(50) of 180 and 580 nM, respectively. These studies suggest that, in addition to the metalloprotease region of mutalysin I, the disintegrin-like domain also participates in the inhibitory effect. The proteolytic activity of mutalysin II against dimethylcasein and fibrin was completely abolished by alpha2-macroglobulin (alpha2-M). The stoichiometry of inhibition was 1.0 mol of enzyme per mol of alpha2-M. In contrast, the proteolytic effect of mutalysin I against the same substrates was not significantly inhibited by alpha2-M. Therefore, the data explain why mutalysin I contributes significantly not only to local but also to systemic bleeding associated with the observed pathological effects of the venom.
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PMID:Action of metalloproteinases mutalysin I and II on several components of the hemostatic and fibrinolytic systems. 1096 87

A series of zinc(II) and magnesium(II) alkoxides based upon a beta-diiminate ligand framework has been prepared. [(BDI-1)ZnO(i)Pr](2) [(BDI-1) = 2-((2,6-diisopropylphenyl)amido)-4-((2,6-diisopropylphenyl)imino)-2-pentene] exhibited the highest activity and stereoselectivity of the zinc complexes studied for the polymerization of rac- and meso-lactide to poly(lactic acid) (PLA). [(BDI-1)ZnO(i)()Pr](2) polymerized (S,S)-lactide to isotactic PLA without epimerization of the monomer, rac-lactide to heterotactic PLA (P(r) = 0.94 at 0 degrees C), and meso-lactide to syndiotactic PLA (P(r) = 0.76 at 0 degrees C). The polymerizations are living, as evidenced by the narrow polydispersities of the isolated polymers in addition to the linear nature of number average molecular weight versus conversion plots and monomer-to-catalyst ratios. The substituents on the beta-diiminate ligand exert a significant influence upon the course of the polymerizations, affecting both the degree of stereoselectivity and the rate of polymerization. Kinetic studies with [(BDI-1)ZnO(i)Pr](2) indicate that the polymerizations are first order with respect to monomer (rac-lactide) and 1.56 order in catalyst. Polymerization experiments with [(BDI-1)MgO(i)Pr](2) revealed that this complex is extremely fast for the polymerization of rac-lactide, polymerizing 500 equiv in 96% yield in less than 5 min at 20 degrees C.
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PMID:Polymerization of lactide with zinc and magnesium beta-diiminate complexes: stereocontrol and mechanism. 1145 57

Laboratory- and pilot-scale racemic polylactides (PLA50) were synthesized in the presence of stannous octoate (SnOct2) or zinc-metal as initiators in the absence of alcohol. The resulting polymers were processed by compression molding or injection molding depending on the batch scale. The hydrolytic degradation of compression-molded samples selected to be comparable was investigated first in order to show the influence of the initiator system. Differences in water uptake were found between PLA50-Zn (zinc-metal initiation) and PLA50-Sn (SnOct2 initiation). PLA50-Zn being much more hydrophilic. PLA50-Sn exhibited a slower molecular weight decrease and delayed onsets of weight loss, release of acidity and stereocomplex formation, with respect to PLA-Zn. The concentration in residual tin in PLA50-Sn increased from 306 to 795 ppm during aging. In the case of PLA50-Zn the residual metal remains constant at ca. 40 ppm. In a second series of experiments, high molecular weight PLA50 different in characteristics and in initiator, synthesized under pilot-scale, were compared. The effects of the initiator on the degradation of the polymers well agreed with laboratory-scale findings, differences in hydrophobicity being enlarged by the up scaling. PLA50-Sn polymers appeared much more degradation resistant than PLA50-Zn ones. Contributions of the other characteristics (e.g. molecular weight, purity, stereoregularity, processing) were shown to be important as well.
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PMID:Influence of polymerization conditions on the hydrolytic degradation of poly(DL-lactide) polymerized in the presence of stannous octoate or zinc-metal. 1179 33


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