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At least 109 records · Page 6Linked to original sources
PubMed1988

Comparative effects of ethylene glycol and ethylene glycol monomethyl ether exposure on hematopoiesis and histopathology in B6C3F1 mice.

Ethylene Glycol (EG) or Ethylene Glycol Monomethyl Ether (EGMME) was administered by gavage to both sexes of B6C3F1 mice for 4 consecutive days at total doses of 200, 400, and 1000 mg/kg body weight. Bone marrow parameters were examined on days 1, 5, and 14 after the final treatment. Exposure to EG produced hypocellularity and suppression of granulocyte-macrophage progenitor (CFU-C) colony formation in both sexes on days 1 and 5 postexposure. Values returned to normal by day 14 in the female mice but not in the males. Erythropoiesis, as measured by 59Fe incorporation and quantitation of erythroid precursors in culture (CFU-E), revealed no effect in female mice and affected male mice at the high dose only. In contrast, EGMME exposure in female mice resulted in inhibition of erythropoiesis. There was also a pronounced effect on white blood cells with decreased peripheral counts, and decreases in the number of CFU-C's cultured from marrow cells. The effect of EGMME was also seen at the lower dose levels and was sustained through the 14-day evaluation period. In addition, EGMME caused a 20% decrease in testicular weight, which was shown microscopically to be a segmented degeneration of seminiferous tubules, an effect not found with EG. This study demonstrates that EGMME is more myelotoxic in mice than EG and that pancytopenia is more pronounced in males, while erythropoiesis is more affected in females.

Animals↗
PubMed2002

Modification of capillary electrophoresis capillaries by poly(hydroxyethyl methacrylate), poly(diethylene glycol monomethacrylate) and poly(triethylene glycol monomethacrylate).

Modification of capillary electrophoresis (CE) capillaries by poly(hydroxyethyl methacrylate) (poly(HEMA), poly(diethylene glycol monomethacrylate) (poly(DEGMA) and poly(triethylene glycol monomethacrylate) (poly(TEGMA), was studied. Methods based on physical adsorption of the modifier and on its chemical binding were compared on the basis of the electroosmotic flow (EOF) reproducibility, the EOF dependence on the pH, the symmetry of the peak of positively charged tyramine, the stability of the coating and the separation of standard and milk proteins in the modified capillaries. Reproducible coatings were obtained by chemical binding of the polymers to the capillary walls and by coating with a solution of a polymer, as also demonstrated by the atomic force microscopy.

Adsorption↗
PubMed2002

Effect of poly(ethylene glycol) molecular weight on tensile and swelling properties of oligo(poly(ethylene glycol) fumarate) hydrogels for cartilage tissue engineering.

This study was designed to determine the effect of changes in poly(ethylene glycol) (PEG) molecular weight on swelling and mechanical properties of hydrogels made from a novel polymer, oligo(poly(ethylene glycol) fumarate) (OPF), recently developed in our laboratory. Properties of hydrogels made from OPF with initial PEG molecular weights of 860, 3900, and 9300 were examined. The PEG 3900 formulation had a tensile modulus of 23.1 +/- 12.4 kPa and percent elongation at fracture of 53.2 +/- 13.7%; the PEG 9300 formulation had similar tensile properties (modulus: 16.5 +/- 4.6 kPa, elongation: 76.0 +/- 26.4%). However, the PEG 860 gels had a significantly higher modulus (89.5 +/- 50.7 kPa) and a significantly smaller percent elongation at fracture (30.1 +/- 6.4%), when compared with other formulations. Additionally, there were significant differences in percent swelling between each of the formulations. Molecular weight between crosslinks (M(c)) and mesh size were calculated for each OPF formulation. M(c) increased from 2010 +/- 116 g/mol with PEG 860 to 6250 +/- 280 g/mol with PEG 9300. Mesh size calculations showed a similar trend (76 +/- 2 A for PEG 860 to 160 +/- 6 A for PEG 9300). It was also found that these hydrogels could be laminated if a second layer was added before the first had completely crosslinked. Mechanical testing of these laminated gels revealed that the presence of an interfacial area did not significantly alter their tensile properties. These results suggest that the material properties of OPF-based hydrogels can be altered by changing the molecular weight of PEG used in synthesis and that multilayered OPF hydrogel constructs can be produced, with each layer having distinct mechanical properties.

Absorption↗
PubMed2005

Effect of the covalent modification with poly(ethylene glycol) on alpha-chymotrypsin stability upon encapsulation in poly(lactic-co-glycolic) microspheres.

The effectiveness of the covalent modification of alpha-chymotrypsin with methoxy poly(ethylene glycol) (PEG) to afford its stabilization during encapsulation in poly(lactic-co-glycolic) acid (PLGA) microspheres by a solid-in-oil-in-water method was investigated. alpha-Chymotrypsin was chemically modified with PEG (M(w) = 5000) using molar ratios of PEG-to-chymotrypsin ranging from 0.4 to 96. Various conjugates were obtained and the amount of PEG modification was determined by capillary electrophoresis. In this investigation, only those conjugates with PEG/chymotrypsin molar ratios between approximately 1 and 8 were considered because higher levels of modification caused protein instability even before encapsulation. The stability and functionality of the chymotrypsin formulations were investigated before encapsulation by measuring enzyme kinetics, thermal stability, and tertiary structure intactness, and after the initial lyophilization process by determining the secondary structure content. These stability parameters were related to select ones after encapsulation in PLGA microspheres (specifically, the amount of insoluble aggregates, residual enzyme activity, and magnitude of protein structural perturbations). The results show that the more stable the protein conformation before encapsulation was, the higher was the retention of the specific activity after encapsulation. In contrast, no relationship was found between the protein stability before encapsulation and the magnitude of encapsulation-induced protein aggregation. Even the lowest level of modification (PEG-to-chymotrypsin molar ratio of 0.7) drastically reduced the amount of insoluble aggregates from 18% for the nonmodified protein to 4%. The results demonstrate that PEG modification was able to largely prevent chymotrypsin aggregation and activity loss upon solid-in-oil-in-water encapsulation in PLGA microspheres. It is demonstrated that it is essential to optimize the degree of protein modification to ascertain protein stability upon encapsulation.

Capsules↗
PubMed1987

A comparison of developmental toxicity evident at term to postnatal growth and survival using ethylene glycol monoethyl ether, ethylene glycol monobutyl ether and ethanol.

This study was designed to compare an abbreviated evaluation of uterine contents at term (teratology probe) with a modified Chernoff-Kavlock assay (postnatal study), [Chernoff N, Kavlock RJ: J Toxicol Environ Health 10:541-550, 1982]. Mice were intubated during gestation and were evaluated for signs of toxicity. In the teratology probe, uterine contents were examined at term. In the postnatal study, offspring were examined and weighed through day 22 postpartum. Ethylene glycol monoethyl ether (EGEE) produced embryo lethality and malformations, and decreased fetal weight at a dose level which was not maternally toxic in the teratology probe. In the postnatal study, EGEE decreased litter size and neonatal body weight; while litter size continued to decrease beyond the neonatal period, body weights of surviving pups were not significantly different from control. Pups exposed prenatally to EGEE developed kinked tail which was not apparent in fetuses or neonates. Maternally toxic dose levels of ethylene glycol monobutyl ether and ethanol were associated with increased embryo lethality in teratology probe studies. In postnatal studies, there were no significant effects on pup growth or survival at maternally toxic dose levels. Preliminary conclusions regarding maternal and developmental toxicity were comparable based on the teratology probe or postnatal study. Both assays measure litter size and offspring weight, but the teratology probe measures resorption incidence which may be a more sensitive index of prenatal death than number of live born. Neither fetal weight nor neonatal weight reliably predict permanent alteration of growth. A postnatal study permits detection of internal malformations or functional defects which reduce postnatal survival and gross abnormalities which appear postnatally.

Animals↗
PubMed1996

Degradation behaviour of block copolymers containing poly(lactic-glycolic acid) and poly(ethylene glycol) segments.

The degradation behaviour of a new class of multi-block copolymers containing poly(D,L-lactic-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) segments was studied under conditions mimicking those found in biological fluids. The dissolution times of the new PLGA-PEG multi-block copolymers mainly depend on the length of the PEG segments present in their structure, i.e., on their PEG content on a weight/weight basis. At higher PEG contents, partially degraded PLGA segments are brought in solution by attached PEG segments. In all cases, the dissolution rates decrease by increasing the total surface area of the specimens tested.

Adsorption↗
PubMed1986

A subchronic dermal exposure study of diethylene glycol monomethyl ether and ethylene glycol monomethyl ether in the male guinea pig.

Diethylene glycol monomethyl ether (DEGME) has been selected as a replacement anti-icing additive for ethylene glycol monomethyl ether (EGME) in Navy jet aircraft fuel. This experiment was performed to determine whether DEGME produced similar toxicity to EGME following dermal exposure. Male guinea pigs were dermally exposed to 1.00, 0.20, 0.04, or 0 (control) g/kg/day DEGME for 13 weeks, 5 days/week, 6 hr/day. Another group of animals was similarly exposed to 1.00 g/kg/day EGME. Body weights as well as testicular and splenic weights were reduced as a result of exposure to EGME, DEGME-exposed animals exhibited decreased splenic weight in the high- and medium-dose (1.00 and 0.20 g/kg/day) exposure groups only. Hematologic changes in EGME-exposed animals included mild anemia with increased erythrocytic mean corpuscular volumes and a lymphopenia with increased neutrophils. Similar hematological changes were not observed in any animals exposed to DEGME. Serum creatine kinase activity was increased in animals exposed to EGME, and serum lactate dehydrogenase activity was increased in EGME and 1.00 g/kg/day DEGME-exposed animals. In general, DEGME produced minimal toxicological changes following dermal exposure, whereas the toxicological changes observed following similar exposure to EGME were much more profound.

Administration, Topical↗
PubMed1990

Reproductive effects of diethylene glycol and diethylene glycol monoethyl ether in Swiss CD-1 mice assessed by a continuous breeding protocol.

Diethylene glycol (DEG) and diethylene glycol monoethyl ether (DEGEE) were evaluated for reproductive toxicity in CD-1 mice using a continuous breeding protocol. Compounds were administered in the drinking water at 0, 0.35, 1.75, and 3.5% w/v (DEG) or 0, 0.25 1.25, and 2.5% w/v (DEGEE). Exposure of the breeding pairs to 3.5% DEG for 14 weeks produced statistically significant decreases in the number of litters per pair, live pups per litter, proportion of pups born alive, and live pup weight. There was also a significant increase in the cumulative days to litter and a significant decrease in the number of pairs producing the third, fourth, and fifth litters for the 3.5% DEG-exposed mice. A crossover mating trial of the F0 mice to determine the affected sex was inconclusive, but suggested that offspring development was compromised in females exposed to 3.5% DEG. Slight maternal (F0) toxicity was noted for the 3.5 DEG group (7% decrease in body weight). The F1 generation, at 3.5% DEG, had decreased body weights at birth and exhibited poor postnatal survival. At the intermediate dose of DEG, body weights of both sexes were depressed at weaning, at onset of mating, and at necropsy. However, no adverse effects on reproduction were observed. DEGEE had no effect on reproduction in the F0 or F1 generation mice despite a 34% decrease in cauda epididymal sperm motility in the F1 males at 2.5% DEGEE. Other signs of toxicity observed in these F1 mice included increased relative liver weights. These data indicate that DEG is a reproductive toxicant in Swiss mice affecting fertility and reproductive performance, albeit at high doses (equivalent to 6.1 g/kg/day). However, its monoethyl derivative, DEGEE, is without adverse effects on fertility and reproductive performance.

Animals↗
PubMed1992

The effect of ethylene glycol monomethyl ether and diethylene glycol monomethyl ether on hepatic gamma-glutamyl transpeptidase.

In this paper, we determined whether ethylene glycol monomethyl ether (EGME) and diethylene glycol monomethyl ether (diEGME) induce hepatic gamma-glutamyl transpeptidase activity. Male adult Wistar rats weighing 220 g were used as experimental animals. EGME (100, 300 mg/kg per day) and diEGME (500, 1000, 2000 mg/kg per day) were administered by gavage for 1, 2 or 5 days or 4 weeks. In the 4-week study, experimental animals were administered EGME or diEGME once a day orally, 5 days/week. EGME treatment increased the serum gamma-glutamyl transpeptidase (GGT) level significantly, however, diEGME did not. The activities of three other enzymes (SGOT, SGPT and ALP) in serum were not altered by EGME or diEGME treatment and thus there was no biochemical indices of hepatic damage by EGME or diEGME. EGME treatment increased the GGT activities in the liver and lungs. Of the organs examined, the induction of GGT was the greatest in the liver. The inducibility in the liver was 216% for the 5-day treatment and 460% for the 4-week treatment. A dose-dependent increase of hepatic microsomal GGT activity by EGME was observed. On the other hand, renal GGT activities were declined to 72% and 60% of control by the 5-day and 4-week EGME treatments, respectively. DiEGME did not affect the GGT activities in any of the tissues except those of the brain. In the histochemical study, most hepatocytes at the periportal zones were stained with GGT staining after the 4-week treatment. However, the hepatocytes at the central zones were negative.

Animals↗
PubMed2005

Preparation and evaluation of poly(polyethylene glycol methyl ether acrylate-co-polyethylene glycol diacrylate) monolith for protein analysis.

A poly(polyethylene glycol methyl ether acrylate-co-polyethylene glycol diacrylate) monolith was prepared by UV-initiated polymerization. Methanol and ethyl ether were selected as porogens from a variety of organic solvents to achieve the desirable characteristics of the monolith. The preparation of the monolith could be achieved within 10 min. The monolith was macroscopically homogeneous, had low flow resistance, and did not swell or shrink significantly in tetrahydrofuran. Inverse size-exclusion data indicate that the monolith had a total porosity of 75.4% and an internal porosity of 9.1%. The monolith could be used for size-exclusion separation of peptides, although it could not separate proteins with molecular masses between 10 and 100 K due to its unique pore size distribution. It was found to resist adsorption of proteins in capillary liquid chromatography when using 100 mM phosphate buffer (pH 7.0) containing 0.5 M NaCl. Complete recovery of both acidic and basic proteins was achieved. The monolith can be used for applications in which inert materials are required for protein analysis.

Acrylates↗
PubMed2005

Mixed micelles made of poly(ethylene glycol)-phosphatidylethanolamine conjugate and d-alpha-tocopheryl polyethylene glycol 1000 succinate as pharmaceutical nanocarriers for camptothecin.

Micelles from the mixture of poly(ethylene glycol)-phosphatidyl ethanolamine conjugate (PEG-PE) and d-alpha-tocopheryl polyetheyene glycol 1000 succinate (TPGS) were prepared loaded with the poorly soluble anticancer drug camptothecin (CPT). The solubilization of CPT by the mixed micelles was more efficient than with earlier described micelles made of PEG-PE alone. CPT-loaded mixed micelles were stable upon storage and dilution and firmly retained the incorporated drug. The cytotoxicity of the CPT-loaded mixed micelles against various cancer cells in vitro was remarkably higher than that of the free drug. PEG-PE/TPGS mixed micelles may serve as pharmaceutical nanocarriers with improved solubilization capacity for poorly soluble drugs.

Animals↗
PubMed2006

Diethylene glycol monomethyl ether, ethylene glycol monomethyl ether and the metabolite, 2-methoxyacetic acid affect in vitro chondrogenesis.

Diethylene glycol monomethyl ether (DEGME), ethylene glycol monomethyl ether (EGME) and their common metabolite, methoxyacetic acid (MAA) have been associated with adverse reproductive effects. The objective of this research is to investigate the effects of DEGME, EGME and MAA on in vitro chondrogenesis and the mechanisms by which these effects occur. Micromass cultures were exposed to DEGME, EGME or MAA for 5 days and proteoglycan abundance and cell proliferation determined. Longer-term 9- and 14-day cultures were exposed to MAA and apoptosis analyzed. All three chemicals decreased proteoglycan abundance and cell proliferation at the highest dose tested (100 microL/mL). However, only MAA showed a dose-dependent effect for both parameters at 0.01, 10, and 100 microL/mL. Furthermore, micromass cultures show an increase in apoptotic cells which when treated with MAA suggest that cell death could result from induced apoptosis. These results suggest that effects of DEGME and EGME are the result of generalized toxicity, but their metabolite MAA induces mitochondrial-mediated apoptosis during in vitro chondrogenesis.

Acetates↗
PubMed2003

Polystyrene nanoparticles based on poly(butyl methacrylate-g-methoxypoly(ethylene glycol)) and poly(methyl methacrylate-g-methoxypoly(ethylene glycol)) graft copolymers.

The solubilization of styrene by poly(butyl methacrylate-g-methoxypoly(ethylene glycol)) and poly(methyl methacrylate-g-methoxypoly(ethylene glycol)) graft copolymers has been examined. From turbidity measurements the solubility limit of the monomer in the micelles was obtained and the distribution coefficients were evaluated. Dynamic light scattering revealed that below the solubility limit, solubilization leads to a slight increase in micelle size, while above the solubility limit, there is a dramatic increase in particle size and turbidity as oil-in-water emulsions are formed through coalescence of monomer-swollen micelles. Polymerizations carried out below the solubility limit using the graft copolymer micelles as templates resembled microemulsion polymerizations in nature and led to very fine sterically stabilized polystyrene latex particles. Through careful control of the monomer concentration and the polymerization temperature it was possible to obtain spherical nanosize latex particles with similar size to those of the micelle precursors (10 nm) up to 11% monomer by weight. Polymerizations above the solubility limit, on the other hand, showed similarities with emulsion polymerizations and resulted in larger particles with higher polydispersity.

Emulsions↗
PubMedDate not supplied

Accelerated clearance of polyethylene glycol-modified proteins by anti-polyethylene glycol IgM.

Tumor therapy by the preferential activation of a prodrug at tumor cells targeted with an antibody-enzyme conjugate may allow improved treatment efficacy with reduced side effects. We examined antibody-mediated clearance of poly(ethylene glycol)-modified beta-glucuronidase (betaG-sPEG) as a method to reduce serum concentrations of enzyme and minimize systemic prodrug activation. Enzyme-linked immunosorbent assay and immunoblot analysis of two monoclonal antibodies generated by immunization of BALB/c mice with an antibody-betaG-sPEG conjugate showed that mAb 1E8 (IgG1) bound betaG and betaG-sPEG whereas mAb AGP3 (IgM) bound poly(ethylene glycol). Neither antibody affected the betaG activity. mAb 1E8 and AGP3 were modified with 36 and 208 galactose residues (1E8-36G and AGP3-208G) with retention of 72 and 48% antigen-binding activity, respectively, to target immune complexes to the asialoglycoprotein receptor on liver cells. mAb 1E8 and AGP3 cleared betaG-PEG from the circulation of mice as effectively as 1E8-36G and AGP3-208G, respectively. mAb AGP3, however, cleared betaG-sPEG more completely and rapidly than 1E8, reducing the serum concentration of betaG-sPEG by 38-fold in 8 h. AGP3 also reduced the concentration of an antibody-betaG-sPEG conjugate in blood by 280-fold in 2 h and 940-fold in 24 h. AGP3-mediated clearance did not produce obvious damage to liver, spleen, or kidney tissues. In addition, AGP3 clearance of betaG-sPEG before administration of BHAMG, a glucuronide prodrug of p-hydroxyaniline mustard, prevented toxicity associated with systemic activation of the prodrug based on mouse weight and blood cell numbers. AGP3 should be generally useful for accelerating the clearance of PEG-modified proteins as well as for improving the tumor/blood ratios of antibody-betaG-PEG conjugates for glucuronide prodrug therapy of cancer.

Aniline Mustard↗
PubMed2002

QSAR modeling of the adult and developmental toxicity of glycols, glycol ethers and xylenes to Hydra attenuata.

Autocorrelation descriptors encoding lipophilicity, molar refractivity, the H-bonding acceptor ability and H-bonding donor ability of the molecules were used to describe glycols, glycol ethers, and xylenes characterized by their adult and developmental toxicities to Hydra attenuata. A PLS regression analysis was employed to derive a QSAR model allowing to simulate both endpoints. Comparisons were made with classical regression analyses using the 1-octanol/water partition coefficient as molecular descriptor.

Age Factors↗
PubMed1998

Comparison of topical therapy for striae alba (20% glycolic acid/0.05% tretinoin versus 20% glycolic acid/10% L-ascorbic acid).

BACKGROUND: Topical treatment of striae rubra with 0.1% tretinoin and laser treatment of striae rubra and alba with the 585-nm pulsed dye laser are proven therapeutic options. However, little efficacy has been shown for treatment of striae alba topically, and the laser is currently not a suitable treatment option for darker ethnic skin types. OBJECTIVE: The purpose of this study was to demonstrate that selected commercial topical agents can improve the appearance of striae alba. METHODS: Ten patients of varying skin types (I-V) having straie distensae alba on the abdomen or thighs were selected to evaluate the effectiveness of two topical treatment regimens. Patients were placed on daily topical application of 20% glycolic acid (MD Forte) to the entire treatment area. In addition, the patients applied 10% L-ascorbic acid, 2% zinc sulfate, and 0.5% tyrosine to half to the treatment area and 0.05% tretinoin emollient cream (Renova) to the other half of the treatment area. The creams were applied on a daily basis for 12 weeks. Improvement was evaluated at 4 and 12 weeks in an objective unblinded fashion at the follow-up visits, a objective blinded fashion by visual grading at the conclusion of the study, and in an objective blinded fashion with profilometry. Additionally, histopathologic analysis was performed. RESULTS: Analysis of these data reveals: 1) both regimens can improve the appearance of stretch marks; 2) these topical therapy regimens are safe and effective in study patients with minimal irritation; 3) elastin content within the reticular and papillary dermis can increase with topical 20% glycolic acid combined with 0.05% tretinoin emollient cream therapy; 4) both regimens increased epidermal thickness and decreased papillary dermal thickness in treated stretch marks when compared with untreated stretch marks; 5) combined epidermal and papillary dermal thickness in stretch marks treated with either topical regimen approaches that of normal skin; and 6) profilometry can objectively measure differences in skin texture associated with striae treatments when compared to controls, however, it is not sensitive enough to justify comparison or quantitative improvements between similarly effective treatments.

Abdomen↗
PubMed1986

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

The safety and efficacy of a conjugate of pyridoxalated hemoglobin and polyethylene glycol (pyridoxalated PEG hemoglobin) were evaluated after administration to rats. The LD50 (lethal dose for 50% survival of group) of pyridoxalated polyethylene glycol (PEG) hemoglobin was greater than 200 ml/kg. Any pro- or anticoagulation activity was not demonstrated in in vitro coagulation tests. One day after 70% exchange-transfusion with pyridoxalated PEG hemoglobin, slight elevations of the serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase, and blood urea nitrogen values, which were 101.7 +/- 22.6 IU/L, 33.3 +/- 7.2 IU/L, and 23.1 +/- 1.4 mg/dl, respectively, were observed. However, these values were in the normal range after 3 days. With greater than 90% exchange-transfusion, all rats exchange-transfused with pyridoxalated PEG hemoglobin survived for greater than 2 weeks in contrast to the death of all the rats exchange-transfused with stroma-free hemoglobin or albumin.

Animals↗
PubMed1991

In vitro studies of water activity and bacterial growth inhibition of sucrose-polyethylene glycol 400-hydrogen peroxide and xylose-polyethylene glycol 400-hydrogen peroxide pastes used to treat infected wounds.

Water activity and bacterial growth inhibition have been studied in formulations comprising either sucrose or xylose along with polyethylene glycol 400 and hydrogen peroxide. The pastes are chemically stable for 6 months if stored at 2 to 8 degrees C and have been shown to lower water activity to levels below those essential for bacterial growth and to be bactericidal even when diluted up to 50% with serum. Of the organisms tested, Staphylococcus aureus proved the least susceptible to the bactericidal effects of these pastes, and candida and gram-negative organisms proved the most susceptible. Pastes without hydrogen peroxide were less rapidly bactericidal than pastes with hydrogen peroxide, while polyethylene glycol 400 itself was found to have considerable antimicrobial activity. It is suggested that sucrose paste may be of benefit as a treatment for infected and malodorous wounds.

Animals↗