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At least 55 records · Page 3Linked to original sources
PubMed1983

Antibodies against polyethylene glycol produced in animals by immunization with monomethoxy polyethylene glycol modified proteins.

Antibodies to polyethylene glycol (PEG) were raised in rabbits by immunization with monomethoxy polyethylene glycol modified ovalbumin (OA), bovine superoxide dismutase (SOD), and ragweed pollen extract (Rag), given in Freund's complete adjuvant (FCA). Immunogenicity depended on the nature of the protein and the degree of modification. With modified OA, in the presence of FCA, the majority of animals showed an anti-PEG response. With modified SOD and Rag only a small proportion of animals responded. In the absence of FCA, modified OA, given s.c., did not elicit any anti-PEG antibody response in rabbits and only a weak response in mice. PEG of MW 10,000 and 100,000 given in FCA was found nonimmunogenic in rabbits, and PEG of MW 5.9 X 10(6), given s.c. to mice, showed no or very poor immunogenic properties. Gel diffusion, heterologous passive anaphylaxis and passive hemagglutination were used to demonstrate anti-PEG antibodies raised to PEG-modified proteins. Specificity was confirmed by hapten inhibition of precipitation, inhibition of passive hemagglutination and cross-reactivity tests. PEG of MW greater than or equal to 4,000 produced specific precipitates, smaller molecules acted as monovalent haptens. From hapten inhibition of precipitation by PEG of MW 300 it appears that the antigenic determinant of PEG may be a sequence of 6-7 -CH2CH2O-units. Anti-PEG antibodies can be used analytically. By gel diffusion, Peg was detected in minimal concentrations of 0.1-1 microgram/ml. The clinical relevance of these findings with regard to therapy with PEG-modified enzymes and allergens in humans remains to be established.

Animals↗
PubMed1984

Polyethylene glycol reactive antibodies in man: titer distribution in allergic patients treated with monomethoxy polyethylene glycol modified allergens or placebo, and in healthy blood donors.

Antibodies to polyethylene glycol (PEG) were analyzed in patients with various allergies and in healthy blood donors employing passive hemagglutination. In untreated allergic patients and in healthy blood donors, naturally occurring anti-PEG antibody titers between 32 and 512 were seen in 3.3 and 0.2%, respectively. During hyposensitization with monomethoxy polyethylene glycol modified ragweed extract and honey bee venom, respectively, the patients showed an anti-PEG antibody response. Titers of 32-512 were found in 50% of the patients directly after the first treatment course. After 2 years of treatment the percentage of patients with such titers declined to 28.5%. Mercaptoethanol treatment of sera indicated that the anti-PEG antibodies predominantly were of the IgM isotype. The weak IgM response found in treated patients is considered to be of no clinical significance.

Allergens↗
PubMed1994

Poly-DL-lactic acid: polyethylene glycol block copolymers. The influence of polyethylene glycol on the degradation of poly-DL-lactic acid.

ABA block copolymers of polyethylene glycol and poly-DL-lactic acid were prepared by ring-opening polymerization of DL-dilactide with alpha,omega-dihydroxy polyethylene glycol, Mn 1000 or 2000. The morphology of the resulting copolymers, with PEG:PLA ratios(mol/mol) of 1:2, 1:3 and 1:4, was characterized by DSC and ESR spectroscopy. The rate of water uptake was biphasic, reflecting the contribution of two processes: rapid diffusion of water into the initially miscible PEG and PLA blocks; then a slower rate of hydration possibly due to phase separation and hydrolytic cleavage of the PLA blocks. The rate of hydrolytic degradation of the block copolymers in DI water at 37 degrees C was measured by two methods: weight loss and colorimetric analysis of the carboxy end group concentration resulting from chain scission of PLA blocks. As a result of phase separation, the rate of scission of PLA blocks in the copolymers was similar to that of the PLA homopolymer. The more rapid onset of weight loss of the copolymers, relative to PLA, is attributed to the greater water solubility of PEG-PLA oligomers and their greater diffusivity in the more highly hydrated copolymers.

Biocompatible Materials↗
PubMed2002

An in vitro examination of the impact of polyethylene glycol 400, Pluronic P85, and vitamin E d-alpha-tocopheryl polyethylene glycol 1000 succinate on P-glycoprotein efflux and enterocyte-based metabolism in excised rat intestine.

The potential inhibitory effects of 3 excipients (polyethylene glycol [PEG] 400, Pluronic P85, and vitamin E d-a-tocopheryl polyethylene glycol 1000 succinate [TPGS]) on the P-glycoprotein (P-gp) -mediated efflux of digoxin (DIG) and cytochrome P450 3A (CYP3A) -mediated metabolism of verapamil (VRP) have been examined in an in vitro permeability model. Experiments were conducted utilizing rat jejunal tissue mounted in diffusion chambers and included assessment of the serosal to mucosal (s to m) transport of DIG and the formation of norverapamil (NOR) during the mucosal to serosal transport of VRP, as measures of P-gp efflux and CYP3A metabolism, respectively. The presence of PEG at 1%, 5%, and 20% (wt/vol) reduced both the s to m flux of DIG (by 47%, 57%, and 64%, respectively, when compared to control) and the metabolism of VRP (by 54%, 78%, and 100%) in a concentration-dependent manner. P85 (0.1% wt/vol) significantly reduced s to m DIG flux by 47% and inhibited VRP metabolism by 42%. TPGS had insignificant effects on both metabolism and efflux at a concentration of 0.01% (wt/vol). The P-gp inhibitory effects of PEG and P85 were evident regardless of whether the excipient was added to the mucosal side, the serosal side, or both sides of the tissue. The current data suggest that inclusion of PEG and P85 as solubilizing agents during in vitro permeability assessment may have a significant impact on both drug metabolism and efflux processes. These compounds appear to exert their effects on P-gp primarily via direct transporter inhibition - or indirectly, through effects on buffer osmolarity, membrane fluidity, and/or mitochondrial toxicity and subsequent adenosine triphosphate (ATP) depletion.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Comparison of alumina-polyethylene and metal-polyethylene in clinical trials.

The dimensional changes of hip sockets of Müller-type total endoprostheses is the subject of this article. Regular anteroposterior roentgenographs of the pelvis were taken to determine the orientation of the center of the prosthetic head in relation to the wire marker of the polyethylene cup. Three different materials used for the femoral balls and matched with polyethylene as socket material were investigated, and the results of the displacement of the ball into the socket were compared. Both creep and wear contribute to the dimensional changes of the hip sockets; the proportional amount of each mechanism is not known. Data from laboratory examinations suggest a relatively high rate of creep in the first six months after implantation. With longer periods, the dimensional changes are predominately caused by wear. In the beginning of joint function, measurements show a high rate of the yearly dimensional changes. The head shifts up to 0.5 mm per year and diminishes after five years to rates of 0.1-0.2 mm, respectively. All dimensional changes that exceed a shift of the head of 0.2 mm per year are considered to be unfavorable and to contribute to loosening of the implants. Using metallic balls (Protasul-2), 64% had a wear rate of less than 0.2 mm; of those using Prostasul-10, 77% had lower rates than 0.2 mm. In patients where ceramic balls were implanted, the displacement rate was below 0.2 mm per year in 95%. Therefore, ceramic seems to be the most favorable material.

Aluminum Oxide↗
PubMed1987

[Polyethylene oxide-based artificial antigens. An experimental study of the kinetics of the distribution of polyethylene oxide derivatives].

125I-labeled derivatives of iodaryl-polyethylene oxide with mol. wt. equal to 3 X 10(3), containing and not containing dinitrophenyl (DNP) residues (haptens), were obtained. The capacity for anti-DNP response was shown to be unaffected by the presence of the iodaryl group. The pharmacokinetics of both derivatives of polyethylene oxide were studied in experiments on noninbred white rats receiving these derivatives intravenously in doses of 0.53-0.80 mg/kg. These experiments revealed the following differences in the pharmacokinetics of the derivatives under study: the presence of the DNP group led to an increase in the level of polymer fixation in the body of the animals, particularly in their blood, liver and spleen. Differences in the content of radioactive substances in other organs were not statistically significant.

Animals↗
PubMed1997

Study of the Gelation Process of Polyethylene Oxidea -Polypropylene Oxideb -Polyethylene Oxidea Copolymer (Poloxamer 407) Aqueous Solutions

The gelation process of polyethylene oxidea -polypropylene oxideb -polyethylene oxidea copolymer (poloxamer 407) aqueous solutions is studied by means of FTIR spectroscopy, rheology, and differential scanning calorimetry (DSC). The C-O-C stretching bands of infrared spectra were found to shift toward higher wavenumbers with sol-gel transition, indicating that hydrogen bonding is not the driving force for gelation. Linear viscoelastic data provide an alternative method for gel point determination of these thermoreversible gels. The results obtained with this method are found to coincide with those obtained using DSC. Gel point temperatures determined by these methods are close to 14 degrees C for 25% (w/w) poloxamer 407 solutions and 10 degrees C for 30% (w/w) solutions. In gel state, the elastic modulus (G ') and dynamic viscosity (eta*) are found to be concentration and temperature independent for temperatures ranging from 20 to 35 degrees C. In light of our results, we suggest a mechanism of gelation based on micelles packing and entanglements.

Journal Article↗
PubMed1997

Studies on tumor-promoting activity of polyethylene: inhibitory activity of metabolic cooperation on polyethylene surfaces is markedly decreased by surface modification with collagen but not with RGDS peptide.

Tumor promotion activity of polyethylene (PE) was estimated in terms of the inhibitory potentials on the gap-junctional intercellular communication using the metabolic cooperation assay. The gap-junctional intercellular communication of test cells was inhibited on the PE film, but this inhibitory activity was markedly decreased when the surface of the PE film was immobilized with collagen. These results suggest that the in vivo tumor promotion activity of the untreated PE may be stronger than that of collagen-immobilized PE. On the other hand, surface modification with RGDS peptide, which is well known as the sequence of cell attachment domain in extracellular matrix proteins, did not reduce the promotion activity of PE film. In addition, neither modification with bovine serum albumin nor RGES peptide reduced the activity of PE film. These findings suggest that reduction of the inhibitory activity on gap-junctional intercellular communication by collagen immobilization is not simply due to improved cell adherence via the RGDS sequence but to some cell-cell recognition via collagen molecules essential for the gap-junctional intercellular communication.

Animals↗
PubMed1996

A colorimetric assay for estimation of polyethylene glycol and polyethylene glycolated protein using ammonium ferrothiocyanate.

A colorimetric method for quantitative assay of polyethylene glycol (PEG) described here is based on partitioning of a chromophore present in ammonium ferrothiocyanate reagent from an aqueous to a chloroform phase in the presence of PEG. The method is simple, reproducible, and can detect PEG in amounts as low as 5 microg. It gives a linear response over a range of 5-100 microg. The absence of any interference by proteins makes the assay equally suitable for the estimation of PEG in PEG-protein conjugates. The method was employed to monitor the separation profile of a mixture of free and PEG-5000 coupled to bovine serum albumin during purification through a gel filtration column. In this report we have also demonstrated for the first time an assay method which permits a critical evaluation of pharmacokinetic properties of any PEG-protein conjugate under in vivo conditions.

Animals↗
PubMed1976

Polyethylene glycol-induced mammalian cell hybridization: effect of polyethylene glycol molecular weight and concentration.

The effects of polyethylene glycol (PEG) molecular weight and concentration on mammalian cell hybridization were studied. The peak hybridization-inducing activity with all grades of PEG from 400-6000 was found to occur in the concentration range of 50-55%. However, changes in concentration were seen to have different quantitative effects with different grades of PEG. For monolayer fusions, PEG 1000 at 50% seems to be the optimal combination of PEG molecular weight and concentration, in terms of both efficiency of hybridization and relative insensitivity to dilution effects.

Cell Fusion↗
PubMed2001

Physicochemical and biomechanical examination of surfaces of retrieved polyethylene heads from total hip prostheses with rotating polyethylene head system.

In order to assess whether hydrodynamic lubrication occurs in total hip prostheses with a rotating polyethylene (PE) head system (R-THP), several physicochemical, morphological, and biomechanical tests were carried out. R-THPs have been used in more than 1000 patients since 1970, and 12 PE heads, retrieved from 10 patients after an average of 24.5 years since total hip arthroplasty (THA), were employed for the tests. The weight-bearing area of the PE surface was light yellow in color and considerably oxidized, but no wear scars were observed. In the non-weight-bearing area, in contrast, discoloration and oxidation were hard to detect. The weight-bearing surface of the PE head became smoother with time after THA, and the friction coefficient did not differ significantly from that of an unused PE head. The radial clearance between head and socket decreased at a temperature of 17 degrees C, which is equivalent to the difference between room temperature and the temperature of the human body. Scanning electron microscopy showed a fine undulating pattern, which suggested that hydrodynamic lubrication could occur in the rotating PE head system.

Adult↗
PubMed2004

Polyethylene glycol-polyamidoamine dendritic micelle as solubility enhancer and the effect of the length of polyethylene glycol arms on the solubility of pyrene in water.

Unimolecular dendritic micelles designed as solubility enhancers were obtained by coupling polyethylene glycol (PEG) to Starburst polyamidoamine (PAMAM) dendrimers. Micelles-750, -2000, and -5000 have a generation 3.0 dendrimer core (32 primary amine end groups) and PEG arms with molecular weights of 750, 2000, and 5000, respectively. The conjugate of dendrimer core and PEG was characterized by MALDI-TOF MS and 1H NMR. 1H NMR was also used to estimate the average number of PEG arms on each dendrimer molecule. A typical hydrophobic compound, pyrene, was sonicated in an excess amount together with micelles at 50 degrees C for 6 h to produce its saturated water solution. The change of the solubility of pyrene was monitored at 334 nm, its maximum adsorption wavelength, by UV-VIS spectra. Concentrated micelles tended to dissolve more pyrene. However, there is no obvious linear relationship between micelle type and the amount of pyrene entrapped within micelles. Micelle-2000 could solubilize more pyrene than micelle-750. It is hypothesized that micelle-5000 did not solubilize more pyrene than micelle-2000 because of the PEG shell disruption by adjacent interpenetration of individual micelles when PEG arm length increased.

Dendrites↗
PubMed2002

New formulation of chemical peeling agent: 30% salicylic acid in polyethylene glycol. Absorption and distribution of 14C-salicylic acid in polyethylene glycol applied topically to skin of hairless mice.

Salicylic acid is used in chemical peeling procedures. However, they have caused many side effects, even salicylism. To achieve a salicylic acid peeling that would be safer for topical use, we recently developed a new formulation consisting of 30% salicylic acid in polyethylene glycol (PEG) vehicle. In an extension of our previous research, we studied the absorption of 30% salicylic acid labeled with 14C in PEG vehicle applied topically to the intact and damaged skin of male hairless mice. An ointment containing 3 mg salicylic acid in 10 mg vehicle was applied to both groups. In animals with intact skin, 1 h after application the plasma concentration of radioactivity was 1665.1 ng eq/ml, significantly lower than the 21437.6 ng eq/ml observed in mice with damaged skin. Microautoradiograms of intact skin showed that the level of radioactivity in the cornified cell layer was similar at 6 h after application. However, in damaged skin, the overall level of radioactivity showed a decrease by 3 h after application. In the carcasses remaining after the treated intact and damaged skin had been removed, 0.09 and 11.38% of the applied radioactivity remained, respectively. These findings confirm that 30% salicylic acid in PEG vehicle is little absorbed through the intact skin of hairless mice, and suggest that salicylism related to absorption through the skin of quantities of topically applied salicylic acid is not likely to occur in humans with intact skin during chemical peeling with this preparation. This new preparation of 30% salicylic acid in PEG vehicle is believed to be safe for application as a chemical peeling agent.

Absorption↗
PubMed1988

Gastrointestinal permeability to polyethylene glycol: an evaluation of urinary recovery of an oral load of polyethylene glycol as a parameter of intestinal permeability in man.

The permeability of the gastrointestinal tract was investigated by means of polyethylene glycol (PEG), given orally. The PEG solutions contained oligomers with molecular weights from 414 to 1206. The urinary recovery of ingested PEG was determined by high performance liquid chromatography (HPLC). Considerable inter- and intra-individual variations in recovery were found in a reference group of 33 healthy subjects. Intake of food did not change the recovery of PEG, 6.11% (SEM 0.52, n = 13) compared with that for the reference group, 6.45% (SEM 0.39, n = 33). The PEG recovery in a group of ileostomy patients was 5.86% (SEM 0.62, n = 13). No correlation was found between PEG recovery and small bowel transit time. The lipophillic properties of PEG were determined by measuring the partition coefficients in 1-octanol/water and in methylhexanoate/water systems. From these results, correlated with the values for the hydrodynamic volumes of PEG, it was concluded that the intestinal permeation of PEG observed was probably determined by the hydrophillic/hydrophobic properties of the mucosal membrane, rather than by the presence of intercellular junctions or paracellular pores. The PEG molecules with molecular weights from 414 to 1206 were, therefore, not suitable as solitary probes for permeability studies in man.

Administration, Oral↗
PubMed1988

The 24-hour posttransfusion survival and lifespan of autologous baboon red cells treated with inositol hexaphosphate-polyethylene glycol or inositol hexaphosphate-adenosine triphosphate-polyethylene glycol to decrease oxygen affinity.

Baboon red cells were treated to reduce oxygen affinity by an osmotic-pulse procedure using dimethyl-sulfoxide. Inositol hexaphosphate (IHP) alone or IHP and adenosine triphosphate (ATP) were incorporated into the red cells in the presence of polyethylene glycol (PEG). The procedure produced variable increases in the red cell P50 value, i.e., the partial pressure of oxygen at which 50% of the hemoglobin was saturated. The effect of treatment of autologous baboon red cells on the 24-hour posttransfusion survival value and lifespan T50 value was measured using a double-label procedure. The data demonstrate that the increase in the P50 value of treated red cells was negatively correlated with the 24-hour posttransfusion survival value; the higher the P50 value, the poorer the 24-hour posttransfusion survival value. The 24-hour posttransfusion survival value for nontreated baboon red cells was 90% and the T50 value was 14 days. The IHP-ATP-PEG-treated red cells had significantly higher red cell ATP levels than did IHP-PEG-treated red cells. The 24-hour posttransfusion survival value was 68% for the IHP-ATP-PEG treated red cells and 52% for the IHP-PEG-treated red cells when the increase in P50 ranged from 10 to 20 mm Hg; the lifespan T50 value for both the IHP-ATP-PEG-treated red cells and the IHP-PEG-treated red cells was 15 days. Osmotic pulse treatment produced significant red cell injury manifested by the 24-hour posttransfusion survival value. However, modification of the RBC with IHP-PEG or IHP-ATP-PEG to decrease hemoglobin affinity for oxygen did not affect their lifespan.

Adenosine Triphosphate↗
PubMed1986

Preparation and evaluation of hemoglobin-polyethylene glycol conjugate (pyridoxalated polyethylene glycol hemoglobin) as an oxygen-carrying resuscitation fluid.

Human hemoglobin was pyridoxalated and subsequently coupled with the activated ester of polyethylene glycol (PEG) to provide an oxygen-carrying resuscitation fluid. The PEG conjugate of pyridoxalated hemoglobin (pyridoxalated PEG hemoglobin) has a longer half-life in the circulation (12.8 h) than does hemoglobin (2.2 h) when the solutions are exchange-transfused by approximately 60%. The P50 of pyridoxalated PEG hemoglobin, which is the partial pressure of oxygen at which one-half of the absorbed oxygen is released, was 21.3 +/- 1.4 mm Hg (mean +/- SD, n = 5) (37 degrees C, pH = 7.4), which is close to that of human whole blood (25.9 +/- 0.6 mm Hg). The colloidal osmotic pressure and the viscosity were 36.5 +/- 2.4 mm Hg (n = 5) and 2.6 +/- 0.4 cp (n = 5), respectively. The results indicate that the pyridoxalated PEG hemoglobin solution has favorable properties for use as an oxygen-carrying resuscitation fluid.

Animals↗
PubMed1980

Purification and characterization of polyethylene glycol dehydrogenase involved in the bacterial metabolism of polyethylene glycol.

Polyethylene glycol (PEG) dehydrogenase in crude extracts of a PEG 20,000-utilizing mixed culture was purified 24 times by precipitation with ammonium sulfate, solubilization with laurylbetaine, and chromatography with diethylamino-ethyl-cellulose, hydroxylapatite, and Sephadex G-200. The purified enzyme was confirmed to be homogeneous by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The molecular weight of the enzyme, which appeared to consist of four identical subunits, was 2.4 X 10(5). The enzyme was stable below 35 degrees C and in the pH range of 7.5 to 9.0. The optimum pH and temperature of the activity were around 8.0 and 60 degrees C, respectively. The enzyme did not require any metal ions for activity and oxidized various kinds of PEGs, among which PEG 6,000 was the most active substrate. The apparent Km values for tetraethylene glycol and PEG 6,000 were about 10.0 and 3.0 mM, respectively.

Alcohol Oxidoreductases↗
PubMed2006

Polyethylene glycol and a novel developed polyethylene glycol-nitric oxide normalize arteriolar response and oxidative stress in ischemia-reperfusion.

Polyethylene glycol (PEG) has been shown to repair cell membranes and, thus, inhibit free radical production in in vitro and in vivo models. We hypothesized that PEG and newly developed organic nitrate forms of PEG (PEG-NO) could repair endothelial dysfunction in ischemia-reperfusion (I/R) injury in the hamster cheek pouch visualized by intravital fluorescent microscopy. After treatments, we evaluated diameter and RBC velocity and flow in arterioles, as well as lipid peroxides in the systemic blood, perfused capillary length, vascular permeability, leukocyte adhesion, and amount of von Willebrand factor (vWF) in the blood after I/R injury. A control group was treated with 5,000- or 10,000-Da PEG, and three groups were treated with PG1 (1 NO molecule covalently bound to PEG, 5,170 Da), PG8 (8 NO molecules covalently bound to PEG, 11,860 Da), and PG16 (16 NO molecules covalently bound to PEG, 14,060 Da). All animals received 0.5 mg/0.5 ml. Lipid peroxides increased at 5 and 15 min of reperfusion, whereas diameter, RBC velocity, and blood flow decreased in arterioles after I/R injury. Vascular permeability, leukocyte adhesion, and vWF increased significantly. PEG and PG1 attenuated lipid peroxides and vasoconstriction during reperfusion and decreased leukocyte adhesion and vascular permeability. PG8 maintained lipid peroxides at normal levels, increased arteriolar diameter, flow, and perfused capillary length, and decreased vWF level and leukocyte adhesion (P < 0.05). PG16 was less effective than PG1 and PG8. In conclusion, PEG-NO shows promise as a compound that protects microvascular perfusion by normalizing the balance between NO level and excessive production of free radicals in endothelial cells during I/R injury.

Animals↗