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A theory for the displacement of proteins and viruses with polyethylene glycol.

The displacement action of polyethylene glycol of different molecular weights may be linked to the ability of the polymers to form coiled particles in solution. From conclusions drawn from their sedimentating properties in centrifugal fields the polyethylene glycols of low molecular weights, as expected, are less randomly coiled than those of higher molecular weight. It is suggested that protein molecules have the ability to diffuse into the coils of the polyethylene glycol from which they are excluded when the random coiling increases with increasing polymer concentration. From considerations based on the interaction of the polymer filament with the displaced particle the distribution of the substance between the coils and the intermolecular spaces may be predicted semi-quantitatively.

Chemical Phenomena

Concentration and purification of mycobacteriophages with polyethylene glycol 6000.

Experiments were performed to concentrate and purify mycobacteriophages with polyethylene glycol 6000; 6, 9, and 8 per cent polyethylene glycol 6,000 proved to be optimal concentrations for precipitating phages of Mycobacterium phlei, Mycobacterium smegmatis strain butyricum, and mycobacterium smegmatis strain Rabinowitz, respectively. Preparative polyethylene glycol reverse gradients were constructed for further concentration and purification of the precipitated phages. With the method described, large amounts of crude phage lysates can be concentrated and purified rapidly.

Bacteriological Techniques

The radiation improvement of polyethylene prostheses. A preliminary study.

The radiation crosslinking of high-density polyethylene prostheses was investigated over a wide range of doses in the presence and absence of gaseous crosslinking agents. It was found that in the bulk polymer the crosslinking pattern is completely different from the homogeneous crosslinking that occurs in polymer films. The presence of crosslinking agents causes highly crosslinked polymer to be formed on the surface while the bulk of the polymer is largely unaffected--which is explained in terms of diffusion phenomena. This surface crosslinking has a profound effect on the mechanical properties of the prostheses and restricts cold flow and deformation of the polymer without sacrificing the excellent abrasion-resistance properties of the polyethylene when subjected to high pressures. Based on this research a number of high-density polyethylene knee prostheses have been radiation-crosslinked and the results in vitro appear to be very promising.

Acetylene

Conglutinin binding polyethylene glycol precipitation assay for immune complexes.

An assay for circulating immune complexes is described which uses radiolabelled bovine conglutinin as ligand and polyethylene glycol precipitation as the technique for separating bound ligands. The technique is simple to perform and gives good sensitivity detecting artificial immune complexes. Its use in detecting complexes in systemic lupus erythematosus and Burkitt's lymphoma is described and it is compared with the Clq binding assay also performed with polyethylene glycol. It is suggested that the simultaneous performance of polyethylene glycol assays using radiolabelled Clq and radiolabelled conglutinin may be an advantageous method for screening sera for the presence of immune complexes.

Animals

Giant cell synovitis associated with failed polyethylene patellar replacements.

Destroyed patellar articular surfaces were replaced with a high molecular weight polyethylene prosthesis in two patients. The patellofemoral articulation of the femur consisted of eburnated bone in one case and degenerative cartilage in the other. Both operations failed within one year because of a giant cell synovitis caused by a high volume (0.2 cc) of fine polyethylene (1-100 mu) wear particles. Ultra high molecular weight polyethylene should not be used as a prosthetic bearing surface to articulate against cortical, cancellous or eburnated bone or against degenerative articular cartilage in a major joint.

Aged

The preferential adsorption of hemoglobin to polyethylene.

Hemoglobin adsorption to foreign surfaces has not previously been considered in studies of blood-material interactions, despite the fact that hemoglobin is the most abundant protein present in blood. A hemoglobin-like protein was detected on a number of surfaces exposed to blood plasma, serum, and red cell suspensions. Hemoglobin adsorption to polyethylene from plasma was found to approximately equal the amount of adsorption of albumin and fibrinogen. The high relative affinity of hemoglobin for polyethylene was further confirmed by adsorption isotherm and direct competition experiments. The data from all four experimental methods support the following ranking of plasma protein affinity for polyethylene: Hemoglobin greater than fibrinogen greater than albumin congruent to gamma-globulin.

Adsorption

The production and biology of polyethylene wear debris.

Polyethylene in the form of a concave bearing surface at the hip wears very slowly, and clinical and histological evidence suggests that the volume of debris so released is well tolerated. However, significantly greater volumetric wear rates are produced when (1) polyethylene is used as the convex component of a joint and (2) abrasives such as PMMA or bone enter the joint. Further, large quantities of polyethylene debris lead to the replacement of bone at the bone-cement interface by soft tissue. Evidence is presented which strongly suggests that this mechanism can produce joint component loosening.

Acrylic Resins

Pharmaceutical applications of solid dispersion systems: X-ray diffraction and aqueous solubility studies on griseofulvin-polyethylene glycol 6000 systems.

The X-ray diffraction method was used to characterize physiochemical properties of griseofulvin dispersed in polyethylene glycol 4000 and 6000. Results indicate a negligible or very limited solid solubility of griseofulvin in the pulverized solid dispersions. Pulverization and aging had pronounced effects on the X-ray diffraction spectrum. Results from aqueous solubility studies of griseofulvin in various concentrations of polyethylene glycol 6000 further indicate weak or insignificant interactions between the drug and the carrier. Mechanisms are postulated to account for the reported marked enhancement of dissolution rates and oral adsorption of griseofulvin dispersed in these carriers.

Chemistry, Pharmaceutical

Liquid-phase method for peptide synthesis utilizing photolytic cleavage from a new o-nitrobenzoyl polyethylene glycol support.

Photolysis as a method for removal of a tert-butyloxycarbonyl-protected peptide possessing a free C-terminal carboxyl group from a polystyrene support in the solid-phase method of peptide synthesis was introduced by Rich, D. H. and Gurwara, S. K.((1975) J. Am. Chem. Soc. 97, 1575-1578). Using this basic concept we prepared a photosensitive 3-nitro-4-bromomethylbenzoyl polyethylene glycol support for use in the liquid-phase method of peptide synthesis. Photolytic cleavage of a protected tetrapeptide possessing a free C-terminal carboxyl group from the polyethylene glycol support resulted in a 98% yield compared with a 69% yield for the photolytic leavage from the polystyrene support. This application of photolysis as a cleavage method in liquid-phase peptide synthesis avoids the low yields and rather drastic conditons needed to remove a peptide attached directly to the poly-ethylene glycol support in the conventional liquid-phase method.

Alanine

Comparison of segmented polyether urethane with polyethylene IUDs in rabbits.

A segmented polyether urethane IUD was compared with a polyethylene IUD in rabbits. The contraceptive efficacy of urethane IUDs was excellent. Moreover, the purulent slippery deposit present with the polyethylene IUDs and observed by Davis et al. (1) was absent. Our studies indicate that the polyether urethane IUDs have a high degree of antifertility activity in rabbits and these IUDs have reduced inflammatory response, based on leucocytic infiltration and tissue debris in the uterine lumen. It is suggested that polyether urethane IUDs not requiring copper or other medication can be designed for high contraceptive efficacy, intrauterine compatibility and with the necessary rigidity for proper uterine retention in humans.

Animals

Polyethylene tubes as a model for the root canal.

Polyethylene tubes, closed at both ends with casting wax and with four perforations in the middle, were implanted subcutaneously in rats and evaluated as a research model simulating the root canal. As controls, wax bars and unperforated tubes were implanted. Attention was given to the reaction of the tissue surrounding the perforated empty tube, the tissue reaction to polyethylene and casting wax, and to the displacement of the tubes.

Animals

The effects of overfilled polyethylene tube intraosseous implants in rats.

Polyethylene tubes obturated flush at one end overfilled 2 mm. at the opposite end with unset Grossman's cement and gutta-percha were implanted in rat tibias. Microscopic evaluation of the specimens revealed that (1) the gutta-percha, Grossman's sealer, and polyethylene tubing are well tolerated by rat intraosseous tissue and (2) a canal overextended 2 mm. beyond the apex with Grossman's cement and gutta-percha produces an early mild to moderate inflammatory response which resolves by the end of 30 day's. The overfillings did not significantly compromise the healing of rat intraosseous tissue.

Animals

Concentration of Rous sarcoma virus from tissue culture fluids with polyethylene glycol.

Concentration of Rous sarcoma virus from tissue culture fluids with polyethylene glycol, with and without NaCl or dextran sulfate, resulted in significant and highly variable losses caused by entrapment of virus particles in proteinaceous debris. Treatment of concentrated preparations with Pronase greatly enhanced the recovery of virions. Maximum recovery of virus particles was obtained by the addition of 8% polyethylene glycol and 0.4 M NaCl to tissue culture fluids, followed by Pronase treatment of the concentrated virus preparations.

Animals

Control of extraction of deoxyribonucleic acid and apurinic acid by polyethylene glycol in Feulgen hydrolysis.

The polymer polyethylene glycol combined with hydrochloric acid was used during the hydrolysis stage of the Feulgen method in order to limit the movement of the soluble molecular fragments developed through hydrolytic breakdown of the deoxyribonucleic acid. The diffusion of the purines was not influenced by the addition of concentration of the polymer up to 30%. On the other hand, a substantial retardation of the extraction of deoxyribonucleic acid and apurinic acid was noted. This indicates that deoxyribonucleic acid and apurinic acid are extracted in chains of considerable length. The decrease in diffusion rate was greater at 1 M HCl than at 0.3 and 6 M HCl, which indicates that the deoxyribonucleic acid-apurinic acid fragments are larger at the medium concentration of acid than at the low and high concentrations. The results thus strengthen the view that deoxyribonucleic acid and apurinic acid are extracted in chains during hydrolysis, and that the critical length at which the chains becomes diffusible is one of the main factors determining the form of the Feulgen hydrolysis curve. The use of polyethylene glycol to extend the maximum of the hydrolysis curve, and thus to make the temperature and time of hydrolysis less critical, is recommended.

Apurinic Acid

Studies of membrane fusion. III. Fusion of erythrocytes with polyethylene glycol.

Freeze-fracture electron microscopy has been used to investigate the mechanism of polyethylene glycol-induced cell fusion. Interaction of cells with the high concentrations of polyethylene glycol required for cell fusion results in cell agglutination with large planar areas of very close contact between adjacent cell membranes. An aggregation of intramembrane particles into large patches at the sites of cell-cell contact accompanies cell agglutination. Fusion occurs following the removal of most of the PEG when cells only remain in close contact at small (approximately 0.1 micrometer diameter) plaques of smooth membrane resulting in cells connected by one (or more) small cytoplasmic connexions. Expansion to form spherical fused cells occurs by a process of cell swelling.

Animals

Wear of high-density polyethylene on bone and cartilage.

Wear of high-density polyethylene on bone and cartilage has resulted in a large volume of plastic particles being shed into the two knees and two hips studied. The giant-cell foreign-body reaction of the synovium may not be sufficient to cope with the amount of debris presented and the destruction of the endosteal bone in one hip, caused by the wear particles and movement of the prosthesis, has made revision impossible. Articulation of high-density polyethylene against bone or cartilage either by design or by the failure of alignment of the component must be avoided.

Bone and Bones

A rapid polyethylene glycol assay for gastric intrinsic factor.

The use of polyethylene glycol (mol. wt 4000) in a rapid radioassay for intrinsic factor is reported. The assay is based on the observation that polyethylene glycol precipitates the intrinsic factor-vitamin B12 complex in the presence of serum from patients with pernicious anaemia having auto-antibodies against intrinsic factor. The assay was found highly reproducible (CV 1.8%) and well correlated to the classical method using coated charcoal in the separation step.

Anemia, Pernicious