Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent reports describe an unfavorable noninfective inflammatory response to acidic degradation products in clinical applications of bone fixation devices fabricated from bulk hydrolyzing polyglycolides and polylactides (PGA and PLA). The work described here suggests that poly(ortho esters) (POEs) offer an alternative. By comparison, hydrophobic POEs degrade predominately via surface hydrolysis, yielding first a combination of nonacidic degradation products, followed by alcoholic and acidic products gradually over time. POE specimens proved acutely nontoxic in United States Pharmacopeia tests of cellular, intracutaneous, systemic, and intramuscular implant toxicity. Hot-molded specimens degraded slowly in saline, retaining 92% initial stiffness (1.6 GPa flexion) and retaining 80% initial strength (66 MPa flexion) in 12 weeks. Degradation was almost unaffected by decreasing saline pH from 7.4 to 5.0. This demonstrated the relative hydrophobicity of POEs, since incorporation of small amounts of acid within the polymer markedly increases the degradation rate. Degradation rates were increased substantially by dynamic mechanical loading in saline. This may be true for other degradable polymers also, but no data could be found in the literature. Presumably, tensile loading opens microcracks, allowing water to enter. Solvent cast POE films were strong in tension (30 + MPa tensile yield) and reasonably tough (12-15% elongation to yield). Higher molecular weight films (41-67 kDa) showed no degradation in mechanical properties after 31 days in physiological buffer at body temperature. A 27-kDa film offered similar initial strength and stiffness but began showing mechanical degradation at 31 days. The films showed a decrease in weight with exposure time but no change in either molecular weight or water absorption at 31 days, further supporting the observation that POE degrades by surface hydrolysis rather than by bulk hydrolysis.
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PMID:Evaluation of absorbable poly(ortho esters) for use in surgical implants. 1014 97

Bioabsorbable polymer implants may provide a viable alternative to metal implants for internal fracture fixation. One of the potential difficulties with absorbable implants is the possible toxicity of the polymeric degradation products especially if they accumulate and become concentrated. Accordingly, material evaluation must involve dose-response toxicity data as well as mechanical properties and degradation rates. In this study the toxicity and rates of degradation for six polymers were determined, along with the toxicity of their degradation product components. The polymers studied were poly(glycolic acid) (PGA), two samples of poly(L-lactic acid) (PLA) having different molecular weights, poly(ortho ester) (POE), poly(epsilon-caprolactone) (PCL), and poly(hydroxy butyrate valerate) (5% valerate) (PHBV). Polymeric specimens were incubated at 37 degrees C in 0.05 M Tris buffer (pH 7.4 at 37 degrees C) and sterile deionized water. The solutions were not changed during the incubation intervals, providing a worst-case model of the effects of accumulation of degradation products. The pH and acute toxicity of the incubation solutions and the mass loss and logarithmic viscosity number of the polymer samples were measured at 10 days, 4, 8, 12, and 16 weeks. Toxicity was measured using a bioluminescent bacteria, acute toxicity assay system. The acute toxicity of pure PGA, PLA, POE, and PCL degradation product components was also determined. Degradation products for PHBV were not tested. PGA incubation solutions were toxic at 10 days and at all following intervals. The lower molecular weight PLA incubation solutions were not toxic in buffer but were toxic by 4 weeks in water.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Six bioabsorbable polymers: in vitro acute toxicity of accumulated degradation products. 1014 75

The structural organization of the B1 domain of streptococcal protein G (PGA) has been probed using molecular dynamics simulations, with a particular emphasis on the role of the solvent exposed Ile6 residue. In addition to the native protein (WT-PGA), three single-mutants (I6G-PGA, I6F-PGA, and I6T-PGA), one double-mutant (I6T,T53G-PGA), and three isolated peptide fragments (corresponding to the helix and the two beta-hairpins) were studied in the presence of explicit water molecules. Comparative analysis of the various systems showed that the level of perturbation was directly related to the hydrophobicity and the size of the side chain of residue 6, the internal rigidity of the proteins decreasing in the order I6T-PGA > I6G-PGA > WT-PGA > I6F-PGA. The results emphasized the importance of residue 6 in controlling both the integrity of the sheet's surface and the orientation of the helix in relation to the sheet by modulation of surface/core interactions. The effects of mutations were delocalized across the structure, and glycine residues, in particular, absorbed most of the introduced strain. A qualitative structural decomposition of the native fold into elementary building-blocks was achieved using principal component analysis and mechanical response matrices. Within this framework, internal motions of the protein were described as coordinated articulations of these structural units, mutations affecting mostly the amplitude of the motions rather than the structure/location of the building-blocks. Analysis of the isolated peptidic fragments suggested that packing did not play a determinant role in defining the elementary building-blocks, but that chain topology was mostly responsible.
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PMID:Mechanics and dynamics of B1 domain of protein G: role of packing and surface hydrophobic residues. 1021 Jan 93

The design requirements for bioabsorbable fracture fixation devices for specific applications are as yet unknown. Therefore, a range of initial mechanical properties and degradation kinetics may provide developers with additional choices for the design of absorbable fracture fixation devices. This study evaluated the changes in push-out strength, polymer mechanical properties, and bone mechanical properties of self-reinforced poly(glycolide) (SR-PGA) and poly(ortho ester) (POE) fracture fixation pins implanted into the canine femoral canal for 18 months. Mechanical testing indicated that SR-PGA pins had degraded to a pasty consistency by 3 months, showing complete loss of all mechanical properties. Meanwhile, POE pins showed a simultaneous linear decrease in both compressive strength and stiffness to almost zero by the end of the study period, suggesting that these devices were undergoing surface erosion. However, changes in specimen diameter, which would support this mechanism, were not apparent. The decrease in polymer density after 12 months suggests that there was an increase in bulk erosion for POE devices. This was further supported by the observation of internal polymer resorption noticed in specimen cross-sections after 18 months. This observation appears to be related to the method of polymer processing; hot-compression molding of fine powdered polymer. The appearance of grain boundaries would provide a path for water to penetrate into the bulk polymer and cause autocatalysis in the interior of the implant.
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PMID:Technical note: biomechanical analysis of two absorbable fracture fixation pins after long-term canine implantation. 1042 97

The effect of the helical sense and the helical macrodipole moment of poly(glutamic acid) (PGA) amphiphiles on miscibility in their binary surface monolayers was examined by means of the surface pressure-area isotherm and spectroscopic measurements. Four types of PGA amphiphiles, having different chirality (l or d) and two long alkyl chains at the C- or N-terminus (1 or 2), were successfully prepared by polymerization of the corresponding NCAs. In acidic solutions, these amphiphiles were found to take right-handed or left-handed helical conformation, depending upon the chirality of the glutamic acid unit, and are dispersed in water molecularly without aggregation. On the other hand, the binary mixed monolayer of 1L and 1D provided a marked positive deviation from an ideal mixing curve, while that of the combination of 1L and 2L gave a much smaller negative deviation, suggesting that helical sense would play a more important role in monolayer miscibility. Copyright 1999 Academic Press.
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PMID:Effects of Helical Sense and Macrodipole on Helix Interaction in Poly(glutamic acid) Monolayers at the Air-Water Interface. 1060 53

The effect of polymer chemistry on adhesion, proliferation, and morphology of human articular cartilage (HAC) chondrocytes was evaluated on synthetic degradable polymer films and tissue culture polystyrene (TCPS) as a control. Two-dimensional surfaces of poly(glycolide) (PGA), poly(L-lactide) (L-PLA), poly(D,L-lactide) (D,L-PLA), 85:15 poly(D,L-lactide-co-glycolide) (D,L-PLGA), poly(epsilon-caprolactone) (PCL), 90:10 (D,L-lactide-co-caprolactone) (D,L-PLCL), 9:91 D,L-PLCL, 40:60 L-PLCL, 67:33 poly(glycolide-co-trimethylene carbonate) (PGTMC), and poly(dioxanone) (PDO) were made by spin-casting into uniform thin films. Adhesion kinetics were studied using TCPS and PCL films and revealed that the rate of chondrocyte adhesion began to level off after 6 h. Degree of HAC chondrocyte adhesion was studied on all the substrates after 8 h, and ranged from 47 to 145% of the attachment found on TCPS. The greatest number of chondrocytes attached to PGA and 67:33 PGTMC polymer films, and attachment to PCL and L-PLA films was statistically lower than that found on PGA (p < 0.05). There was no correlation between amount of chondrocyte attachment to the substrates and the substrates' water contact angle. Chondrocytes proliferated equally well on all the substrates resulting in equivalent cell numbers on all the substrates at both day 4 and day 7 of the culture. However, these total cell numbers were reached as a result of a 88- and 42-fold expansion on PDO and PLA, respectively, which was significantly higher than the 11-fold expansion found on TCPS (p < 0.05). The greater fold expansion of the cells on PDO and L-PLA films may be attributed to the availability of space for cells to grow, since their numbers at the start of culture were fewer following the 8 h attachment period. This suggests that regardless of initial seeding density on these degradable polymer substrates (i.e., if some minimum number of cells are able to attach), they will eventually populate the surfaces of all these polymers given sufficient space and time.
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PMID:Human articular chondrocyte adhesion and proliferation on synthetic biodegradable polymer films. 1061 31

Pepsin-solubilized elastin (PSE)-conjugated collagen film was prepared from a collagen matrix with PSE by drying it and crosslinking the constituents with water-soluble carbodiimide or microbial transglutaminase to improve the physical properties of the collagen film. The crosslinking reduced the solubility and improved the thermal stability, the thermal transition properties, and the elasticity of the control film in water. In particular, water-soluble carbodiimide strongly influenced these properties. The PSE-conjugated collagen film showed good permeation by water-soluble tasting substances such as oligosaccharides and amino acids, but poor permeation by polysaccharide, protein, and hydrophobic substances such as retinol and cholesterol.
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PMID:Improvement of the physical properties of pepsin-solubilized elastin-collagen film by crosslinking. 1066 47

This review article deals with the chemistry and biosynthesis of poly-(gamma-glutamic acid) (gamma-PGA) produced by various strains of Bacillus. Potential applications of gamma-PGA as thickener, cryoprotectant, humectant, drug carrier, biological adhesive, flocculant, or heavy metal absorbent, etc. with biodegradability in the fields of food, cosmetics, medicine and water treatments are also reviewed.
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PMID:The production of poly-(gamma-glutamic acid) from microorganisms and its various applications. 1149 75

The influence of solar irradiance and seasons on prostaglandin (PG) and arachidonic acid (AA) content in the marine red alga Gracilaria verrucosa (Huds.) Papenf. (unattached form) was investigated. PGA(2), PGE(2), PGF(2), and 15-keto-PGE(2) were isolated from the alga, quantitatively analyzed as 4-methyl-7-methoxycoumarin esters by high-performance liquid chromatography, and their chemical structures were confirmed by 1H NMR. In June-September, the PG content in the alga was relatively stable (420 microg/g of dry wt. of PGE(2)+PGF(2); 40 microg/g of PGA(2)) and it increased 1.5 times in October. The highest level of PGs was detected in November (2500 microg/g of PGE(2)+PGF(2); 74 microg/g of PGA(2)) when water temperature was fairly low (5-10 degrees C). Algae grown for five months at 50% of incident photosynthetic active radiation (PAR(0)) contained two times less PGE(2) and PGF(2) than algae grown under natural conditions, but the amount of these PG in algae grown at 5% of PAR(0) was close to the normal level. On the contrary, when algae were grown at 5% of PAR(0) the content of PGA(2) increased up to 4 times compared to algae cultivated at 100% PAR(0). In June-November, the amount of AA in total algal lipids slightly varied from 48.9 to 56.7% and did not virtually depend on the light intensity. The probable reasons of the PG content variation in response to environmental factors are discussed.
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PMID:Response of prostaglandin content in the red alga Gracilaria verrucosa to season and solar irradiance. 1173 Aug 70

It has been recognized that adhesion and proliferation of cells on biodegradable polymers such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and poly(lactide-co-glycolide) (PLGA) depend on the surface properties. The chloric acid (CA) treatment of these films was developed to increase surface wettability and to improve adhesion and proliferation of human chondrocytes and NIH/3T3 fibroblasts. The CA-treated films were characterized by the measurement of water contact angle, electron spectroscopy for chemical analysis (ESCA), and scanning electron microscopy (SEM). The changes of the film surface water contact angle gradually decreased with increase of CA treatment time, owing to the oxygen-based functional groups incorporated on the surface by CA treatment and were in the order PGA > PLGA > PLA due to the number of methyl group on the backbone chain. In ESCA analysis, as CA treatment time increased, the carbon (binding energy, approximately 285 eV) ratio decreased in film surfaces, whereas the oxygen (approximately 532 eV) ratio increased. The human chondrocytes from articular cartilage and mouse NIH/3T3 fibroblasts adhered for 1 day and grown for 2 days on the CA-treated films were counted and observed by SEM. As the surface wettability increased, the number of cells adhered and grown on the surface increased. In conclusion, this study demonstrated that the surface wettability of the biodegradable polymer plays an important role for cell adhesion and proliferation behavior for the application of the tissue engineering.
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PMID:Interaction of human chondrocytes and NIH/3T3 fibroblasts on chloric acid-treated biodegradable polymer surfaces. 1202 50


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