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

CHAG, that is, porous hydroxyapatite hydrothermally converted from the calcium carbonate exoskeleton of a coral (genus Goniopora), has been shown to be effective as a scaffold for bone ingrowth. The large pores in the material, however, resulted in low compressive strengths. Compressive testing was performed to assess the changes in mechanical properties by coating the internal surfaces of CHAG with DL-PLA. Plugs of CHAG with thick (3:1 chloroform to DL-PLA by weight), medium (10:1), and thin (30:1) coatings as well as uncoated CHAG were then implanted transcortically in the proximal third of the diaphysis of rabbit tibiae to assess the in vivo response. The mechanical tests demonstrated significantly improved compressive strength, stiffness, and energy absorption for coated specimens compared with uncoated specimens. Coated specimens were not significantly different from canine tibial cancellous bone in strength and stiffness although they achieved only 36% of the energy absorption capacity. Specimens from rabbit tibiae were harvested at 3, 12, and 24 weeks for interface shear strength determination and contralaterally for histological and histomorphometric assessment. At 12 weeks, uncoated CHAG plugs developed an average ultimate interface shear stress of 26.7 MPa compared with 17 MPa for specimens with 30:1 coatings and 8 MPa for specimens with 10:1 and 3:1 coatings. At 24 weeks, there were no significant differences in shear stress between any of the specimens. Histomorphometric assessments showed that the ratio of area fraction of new bone to area fraction of new bone and void space increased from 68-70% for specimens with 3:1 and 10:1 coatings at 3 weeks to 85.5-89.5% at 24 weeks. In comparison, uncoated and 30:1 specimens had area fraction ratios of about 82% at 3 weeks and 93% at 24 weeks. Histologic sections demonstrated direct apposition of new bone to both the coating and the hydroxyapatite as well as degradation of the coating.
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PMID:Mechanical and bone ingrowth properties of a polymer-coated, porous, synthetic, coralline hydroxyapatite bone-graft material. 289 22

Porous hydroxyapatite, converted hydrothermally from the calcium carbon exoskeleton of the coral genus Goniopora (CHAG), has been shown to be effective as a scaffold for bone ingrowth (2,3,5-7,9). However, the large pores in the material resulted in low compressive strengths. In a previous study, we found that microcoating the internal surfaces of CHAG with dilactic-polyactic acid (DL-PLA) improved significantly its compressive properties. The objective of this study was to determine the effect of PLA microcoating on bone ingrowth into CHAG plugs. Plugs of thick- (3:1 chloroform to DL-PLA by weight), medium- (10:1), and thin- (30:1) coated as well as uncoated CHAG were implanted transcortically in the proximal third of the diaphysis of the rabbit tibia. Specimens were harvested at 3, 12, and 24 weeks for mechanical testing and contralaterally for histological and histomorphometric assessment. At 12 weeks, uncoated CHAG plugs developed an average ultimate interface shear stress of 26.7 MPa, compared with 17 MPa for 30:1 and 8 MPa for 10:1 and 3:1 coated specimens. At 24 weeks, there were no significant differences in shear stress among any of the specimens. Histomorphometric assessments showed that the ratio of area fractions of new bone to area fractions of new bone and void space increased from 68-70% for 3:1 and 10:1 coated specimens at 3 weeks, and to 85.5-89.5% at 24 weeks. In comparison, uncoated and 30:1 specimens had area fraction ratios of about 82% at 3 weeks and 93% at 24 weeks. Histologic sections demonstrated direct apposition of new bone to both the coating and the hydroxyapatite as well as degradation of the coating.
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PMID:Bone ingrowth into polymer coated porous synthetic coralline hydroxyapatite. 357 96

Bovine plasma yields fibrinolytically inactive euglobulin fractions, even when prepared in the presence of dextran sulphate. Addition of flufenamate to these solutions only occasionally elicits a slight activity. However, highly fibrinolytic solutions are produced when euglobulins precipitated in the presence of dextran sulphate are exposed to chloroform. Evidence indicates that a plasminogen activator is formed, which subsequently converts plasminogen present in the fractions to plasmin. Bovine euglobulin fractions contain an inhibitor which seems to be specifically directed towards urokinase and not to plasmin or to tissue plasminogen activator. Its inhibiting capacity is decreased after treatment with chloroform.
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PMID:Generation of fibrinolytic activity in bovine plasma by the combined effects of chloroform and dextran sulphate. 616 66

Various methods to determine loading of vaccine in biodegradable polymer microspheres encapsulating tetanus toxoid were evaluated. The microspheres were composed of poly (D-lactic acid) (PLA) and poly (DL-lactic-co-glycolic acid) (PLGA). Dissolution of microspheres in organic solvents such as methylene chloride, chloroform, or dimethyl sulfoxide and extraction of vaccine antigen or total protein with phosphate buffered saline gave variable results which depended upon the characteristics of the microspheres, such as type of polymer, excipients used in the microspheres and formulation conditions. Microspheres made from low molecular weight PLGA polymer and showing a large burst release exhibited up to 25% extraction of antigen whereas microspheres made from PLA microspheres with low burst release showed < 1% extraction. Extraction of total protein with 0.1 N NaOH and 5% sodium dodecyl sulfate showed results similar to those obtained with organic solvent extraction method. Partial digestion of microspheres with 6 N HCl at 60 degrees C for 20 h resulted in approximately 30% loss in TT protein by micro-bicinchoninic acid (BCA) assay. The major problem with this method was strong reactions in the micro-BCA assay of stabilizers, particularly sugars (glucose, sucrose) used in the microsphere formulations. Complete digestion of microspheres with 6 N HCl at 110 degrees C for 20 h or with 13.5 N NaOH at 121 degrees C for 1 h and quantitation of amino acids by a modified ninhydrin assay showed reproducible results on the protein loading in the microspheres. However, this method was affected by the presence of stabilizers, such as gelatin, which contain amino acids. Further, sucrose concentrations higher than 10% caused interference in the ninhydrin assay on samples hydrolyzed with 6 N HCl. In contrast, hydrolysis with 13.5 N NaOH did not show any interference by sucrose. Stabilizers used outside the microspheres for lyophilization purposes may be removed by washing the microspheres before loading determination or by dialysis but stabilizers used inside the microspheres would still cause interference. For reliable determination of total protein in the microspheres containing vaccines, we suggest complete digestion of microspheres with acid or base followed by amino acid analysis by colorimeteric assays such as ninhydrin method or using amino acid analyzers. The method needs to be optimized for each type of formulation to eliminate interference by the excipients. Alternatively, total protein nitrogen in the microspheres may be determined by the Kjel-dahl method if no amino acids or other nitrogen containing stabilizer is used inside the microspheres.
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PMID:Determination of protein loading in biodegradable polymer microspheres containing tetanus toxoid. 917 69

Poly(DL-lactic acid) (PLA) microspheres containing testosterone (T) were prepared by the solvent evaporation process to evaluate their physical properties such as size distribution, shape, drug content, in vivo controlled drug release, pharmacological influences on the prostate gland in castrated rats, and histopathological findings of tissues surrounding the implants. The in vivo release of T from PLA microspheres containing 30 mg of drug obtained with chloroform was continued over a 6-week period. This effect is attributed to high dispersibility of T in the device when obtained with chloroform. Both serum drug levels and prostate gland weight recovery suggested the effects of a long-acting drug delivery system. The histopathological findings showed that the devices used were completely degraded 10 weeks after injection.
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PMID:In vivo characteristics of injectable poly(DL-lactic acid) microspheres for long-acting drug delivery. 987 32

Extraction with Tris-citrate or Tris-NaCl-EGTA improved the yield of phospholipase A2 (PLA2) from ram semen by 40-50 fold over the previously recommended method of extraction by dilute (0.18 N) sulphuric acid. The enzyme activity in the citrate extract deteriorated more rapidly than in Tris-NaCl-EGTA. The semen PLA2 activity was optimum at pH 8.0, heat sensitive at 70 degrees C for 30 min, activated by Ca2+ (although approximately 60% activity was also found in the absence of calcium) and did not exist as a pro-enzyme. The semen PLA2 activity was equally distributed among the sperm and seminal plasma (SP) components of ram semen. However, the low levels of PLA2 activity in the SP of vasectomised rams tend to suggest that PLA2 in the SP fraction may have originated from testicular or epididymal secretions or leakage, from sperm. PLA, in sperm exists as a large molecular weight aggregate, whereas in SP it is present as a smaller aggregate. In addition to PLA2, semen also contained PLA2 inhibitor activities. Inhibition was observed against PLA2s from bee venom, pig pancreas and oviductal extracts. The inhibitory activity is presumed to be due to a large molecular weight protein as the inhibitor activity was not extracted in a chloroform:methanol (2:1; v/v) mixture, it was non-dialysable, precipitated by 10% trichloroacetic acid and destroyed by proteases. The inhibitor activity was distributed in various molecular weight fractions of sperm, SP and SP from vasectomised rams.
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PMID:Studies on the measurement of phospholipase A2 (PLA2) and PLA2 inhibitor activities in ram semen. 1046 98

Microparticles were produced by spray-drying from a high molecular weight polylactide (PLA R207) for the development of long-lasting controlled release systems of vaccines, which may be designed to obviate the need for booster doses. The current investigation considered the effect of both technological parameters (inlet air temperature and spray rate of feed) and polymeric solutions (polymer concentration and nature of organic solvents) on characteristics of microparticles (morphology, size and antigen loading) containing a water-soluble model antigen (bovine serum albumin, BSA). Following parameters chosen, microparticles were characterized by a mean size from 3.08 +/- 0.06 to 9.43 +/- 0.26 microm and a BSA loading from 2.45 +/- 0.13 to 18.20 +/- 2.25% (w/w). The BSA release rate from microparticles varied from 11.17 +/- 2.20 to 92.60 +/- 3.46% in 24 h. The modification of the inlet temperature, the spray-rate of feed or the use of a mixture of dichloromethane/chloroform (DCM/CFM) instead of DCM alone resulted in the modification of the BSA burst release. This burst release was followed by a BSA release rate slower for microparticles with a low BSA loading. Moreover, the increase of the R207 concentration resulted in a decrease of the BSA release rate while the burst release was not modified. SDS-PAGE electrophoresis and isoelectric focusing analyses of the BSA released from microparticles confirmed the preservation of its physicochemical characteristics. Together, results showed that the spray-dried microparticles loaded with hydrophilic antigen could be used as a potential delivery system for the long-lasting controlled release of vaccines.
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PMID:Parameters influencing the antigen release from spray-dried poly(DL-lactide) microparticles. 1084 95

Electrospun fiber mats are explored as drug delivery vehicles using tetracycline hydrochloride as a model drug. The mats were made either from poly(lactic acid) (PLA), poly(ethylene-co-vinyl acetate) (PEVA), or from a 50:50 blend of the two. The fibers were electrospun from chloroform solutions containing a small amount of methanol to solubilize the drug. The release of the tetracycline hydrochloride from these new drug delivery systems was followed by UV-VIS spectroscopy. Release profiles from the electrospun mats were compared to a commercially available drug delivery system, Actisite (Alza Corporation, Palo Alto, CA), as well as to cast films of the various formulations.
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PMID:Release of tetracycline hydrochloride from electrospun poly(ethylene-co-vinylacetate), poly(lactic acid), and a blend. 1199 78

We report the results of a high throughput screening campaign that is aimed to develop a biodegradable polymer-based formulation to deliver active keratinocyte growth factor (KGF) and provide a means to tune the KGF delivery rate. A statistical design strategy was used to prepare and screen a series of polymer blends that were composed of poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and the surfactant sodium bis(ethylhexyl)sulfosuccinate (Aerosol-OT, AOT). Chloroform was the solvent. Our high throughput screening method used a two-tiered assessment strategy. At Level 1, we identified "lead" KFG-loaded formulations that exhibited KGF emission spectra that were the most similar to the native KGF spectrum recorded in buffer. At Level 2, we used steady-state emission and a homogeneous polarization immunoassay strategy to determine the concentration of total and active KGF, respectively, liberated from the lead formulations during biodegradation. After preparing and screening 2500 formulations, we identified several viable, lead formulations. An analysis of the data showed that the combination of PLA, PGA, and AOT were important to yield a high fraction of active KGF upon release from the formulation; no combination of any two together produced an effect as good as the ternary formulation. The optimum formulations that yielded the highest fraction of active KGF upon release had the following general features: PLA/PGA (w/w) near unity, AOT loading of 100-200 mM, water/AOT mole ratio of 10-20, and a pH between 6 and 8. PLA alone cast from chloroform delivered KGF, but that KGF did not bind to anti-KGF antibodies (i.e., it was inactive). We can tune the KGF release kinetics by more than two orders of magnitude while maintaining the KGF activity upon liberation from the formulation by adjusting the PLA molecular weight.
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PMID:Tailored delivery of active keratinocyte growth factor from biodegradable polymer formulations. 1288 13

In order to discover novel invertebrate cytokines from the budding tunicate, Polyandrocarpa misakiensis, we treated the water-insoluble fraction of tunicate homogenates with trypsin. The extracts showed remarkable activities to promote the growth and motility of tunicate cells. The activities were heat-stable and proteinase K-resistant. After anion exchange chromatography, the activities were eluted with detergents such as 0.1% deoxycholic acid. The Fourier transform infrared spectrum indicated large amounts of fatty acids and phospholipids instead of polypeptides in the extracts. Consistently, the activities were extractable with organic solvents such as chloroform. Long chains of n-3 polyunsaturated free fatty acids (FFA), phosphatidylinositol (PI), phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS) were the major components in the lipid-soluble fraction. A cDNA for FFA-releasing enzyme phospholipase A(2) (PLA(2)) was cloned. The expression of this gene could be seen in epidermal cells during budding. The recombinant protein, as in the case of the authentic PLA2, preferred PC and PE as substrates, followed by PS and PI. The resultant FFAs only promoted cell growth, while the remaining lysophospholipids stimulated cell motility. The former contained unsaturated fatty acids (C18:1, C20:5, and C22:6) while the latter did not, suggesting that unsaturated fatty acids are responsible for mitogenic activity in tunicate cells. These results show for the first time that phospholipids and their derivatives are bio-mediators promoting cell growth and cell motility in invertebrates.
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PMID:Phospholipids and their derivatives as mitogen and motogen of budding tunicates. 1499 11


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