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At least 19 recordsLinked to original sources
PubMed1978

Comparison of 14C-labelled polyethylene glycol (PEG) with carrier PEG and 14C-PEG alone as a volume indicator in the human jejunum.

14C-labelled polyethylene glycol (PEG) (5 muCi/l) was used as a non-absorbable marker in human jejunum both with and without carrier PEG (5 g/l). Calculation of net water flux was virtually identical whether or not the carrier PEG was included in the perfusion solution. 14C-PEG alone is a satisfactory non-absorbable marker for perfusion studies in the human jejunum.

Biological Transport↗
PubMed1989

Differential changes in the urinary excretion of two orally administered polyethylene glycol markers (PEG 900 and PEG 4000) in rats after feeding various carbohydrate gelling agents.

The urinary excretion of two orally administered polyethylene glycol markers (PEG 900 and PEG 4000) was measured in rats after feeding various carbohydrate gelling agents. Pectin, guaran, methylcellulose, and carrageenan were added (20% wt/wt) to a fiber-free control diet and were fed for 4 wk prior to the experiment. Excretion of 3H-PEG 900 and 14C-PEG 4000 was measured over a period of 96 h after administration of the markers in the drinking water. In general, the ratio of PEG 4000 to PEG 900 in the urine increased after fiber feeding: from 0.20 in the controls to 0.31, 0.37, 0.29, or 0.27 (medians) in the pectin-, guaran-, methylcellulose-, or carrageenan-fed group, respectively. The pattern of excretion of the two PEG markers in rats fed the fiber-free diet differed from that in the polysaccharide-fed rats. Pectin and guaran, two polysaccharides readily fermented by intestinal bacteria, led to a higher excretion of PEG 4000 but an unaltered excretion of PEG 900, whereas methylcellulose and carrageenan, two polysaccharides more inert against microbial degradation, were associated with a lower excretion of PEG 900 with unchanged excretion of PEG 4000. The study shows that polysaccharides, which may be representative of the soluble portion of dietary fiber, can influence the intestinal permeability of larger molecules. The microbiologically degradable polysaccharides in particular may lead to an increased absorption of larger molecules.

Animals↗
PubMed1986

Safety evaluation of free radical scavengers PEG-catalase and PEG-superoxide dismutase.

Treatment with catalase and SOD (superoxide dismutase) could diminish the damage due to oxygen free radical formation, but these enzymes are rapidly removed from circulation. The covalent attachment of monomethoxypolyethylene glycol (PEG) to catalase and SOD extended their plasma half-lives. Toxicity of PEG-catalase and PEG-SOD was evaluated in mice and rats prior to their use as free radical scavengers. Rodents used in acute, subacute, and subchronic toxicologic studies could tolerate large doses of PEG-catalase and PEG-SOD without developing toxic signs. The conjugates did not affect survival rate, appearance, behavior, food intake, blood chemistry, hematology, or urinalysis. In general, body weight gains, organ weights, and histomorphology were also unaffected. Massive doses of PEG-catalase caused slight weight loss, splenic hypertrophy, and generalized splenic stimulation in mice. Massive doses of PEG-SOD resulted in vacuolation in splenic macrophages in rats. PEG-catalase and PEG-SOD circulated for 3 days and 8 days, respectively, in mice following i.v. or i.m. administration.

Animals↗
PubMed1991

Murine studies using polyethylene glycol-modified recombinant human interleukin 2 (PEG-IL-2): antitumor effects of PEG-IL2 alone and in combination with adoptive cellular transfer.

A polyethylene glycol-modified form of recombinant human IL-2 (PEG-IL-2) was tested for murine antitumor effects in vitro and in vivo. This PEG-IL-2 was demonstrated to retain the in vitro ability to support T cell proliferation, enhance a mixed lymphocyte reaction, and generate lymphokine-activated killer (LAK) cells. It was found to have a circulating half-life in mice 25 times longer than unmodified recombinant IL-2 (RIL-2). Serum levels were detected up to 60 h after a single intravenous injection. When given as a single, intravenous administration the antitumor effect of this material was similar to multiple, repeated bolus doses of RIL-2. PEG-IL-2 was also found to support the in vivo efficacy of adoptively transferred LAK cells and tumor infiltrating lymphocytes (TIL). Using a congenic TIL (Thy 1.1), persistence of adoptively transferred TIL was found to be prolonged with PEG-IL-2 compared to repeated boluses of RIL-2. Four days after transfer, twice as many Thy 1.1 TIL were recoverable from the lungs of mice given PEG-IL-2. These studies show that PEG-IL-2 is a modified lymphokine with significant antitumor activity in murine systems and is superior to bolus RIL-2 in enhancing the survival of adoptively transferred TIL.

Animals↗
PubMed1986

Intestinal permeability in small children during and after rotavirus diarrhoea assessed with different-size polyethyleneglycols (PEG 400 and PEG 1000).

The permeability properties of the small intestinal mucosa was investigated in nine previously healthy children with acute diarrhoea due to rotavirus. The investigation was performed after intake of a mixture in water of polyethyleneglycol molecules (PEG 400 and 1000) ranging from 282 to 1250 dalton in molecular weight. The 6-h urinary recovery of the PEGs was determined with high performance liquid chromatography and used to assess the permeability characteristics of the intestine. The patients served as their own controls and were investigated in the same manner after recovery 3-5 weeks later. A significantly lower urinary recovery of PEG was noted for all molecular sizes (326-1206 dalton) during acute diarrhoea in comparison with the results obtained after recovery (p less than 0.001-0.1). There was also a relatively lesser change in the urinary recovery of larger PEG molecules during infection, as reflected by a higher recovery ratio between 1074 and 370 dalton PEGs. The results indicate profound changes in the permeability characteristics of the intestine during acute rotavirus diarrhoea.

Diarrhea, Infantile↗
PubMed1985

Modelling of intestinal permeability in man to polyethylene glycols (PEG 400 and PEG 1000).

The intestinal permeability barrier was evaluated in four healthy individuals by the 6 h urinary recovery of a mixture of different-sized polyethylene glycols (PEG 400 and PEG 1000) after a liquid meal of probe molecules. The mixture of PEGs contained around 25 different PEG polymers, ranging from about 194 to 1294 dalton in size. Three models were employed to get a condensed formulation of the intestinal barrier, namely a filter function, describing exclusion of molecules due to the molecular weight, and two expressions for ultrafiltration through a pore due to the Stoke-Einstein radius. A factor reflecting unrestricted passage of probe molecules in the size-range used was also included in the mathematical expressions. It was found that a filter function showing half-maximum exclusion at 589-956 daltons (Da) PEG and a pore function yielding a pore-size of 8.0-8.5 A equally well described the intestinal barrier in the four subjects. The results are discussed in relation to structures of the intestinal epithelium that may restrict the passage of molecules.

Capillary Permeability↗
PubMed1986

Gastrointestinal permeability in children with cow's milk allergy: effect of milk challenge and sodium cromoglycate as assessed with polyethyleneglycols (PEG 400 and PEG 1000).

Sixteen children with immediate-type cow's milk allergy were challenged with increasing amounts of cow's milk. Gastrointestinal permeability was investigated before and after challenge by the 6-hr urinary recovery of a mixture of different-sized polyethyleneglycols (PEG 400 and PEG 1000). The results were related to clinical symptoms in the individual patients. The majority of the children displayed changed permeability characteristics after the challenge, both with respect to the maximum uptake of a small test molecule (usually 370 dalton PEG) and/or a large molecule (1074 dalton PEG), and to size-dependent exclusion of probe molecules. When corrected for the dose of milk taken, the children showing the most severe immediate-type symptoms also displayed the greatest alteration of permeability. Treatment with sodium cromoglycate (SCG) before the challenge diminished the effect on the uptake of probe molecules, usually decreased the severity of elicited symptoms, allowing about a ten-fold increase in the milk dose. Cow's milk challenge in healthy children caused only minor permeability changes, whereas challenge in the sensitized subjects significantly changed (increased or decreased) the recovery of a large test molecule. The difference between healthy and allergic subjects was most obvious when correcting for dose of milk ingested. We conclude that oral challenge with cow's milk in allergic subjects affects the mucosal barrier, and peroral treatment with SCG moderates immediate hypersensitivity reactions with respect to both tolerated antigen dose and intestinal permeability properties.

Administration, Oral↗
PubMed1977

Measurements of intestinal permeability using low molecular weight polyethylene glycols (PEG 400). I. Chemical analysis and biological properties of PEG 400.

A new approach to the measurement of intestinal permeability in man has been developed, using low molecular weight polyethylene glycol (PEG 400) as probe molecules. PEG 400 (range of molecular weight 232 to 594) is a mixture of water-soluble molecules of different sizes which can be extracted readily from biological fluids and analyzed by gas-liquid chromatography. PEG 400 is nontoxic, not degraded by intestinal bacteria, not metabolized after absorption, and rapidly excreted in urine. The different-sized molecular components cross the intestinal epithelium at different rates, allowing characterization of the passive permeability properties of the mucosa.

Animals↗
PubMed1985

Gastrointestinal permeability in atopic and non-atopic mothers, assessed with different-sized polyethyleneglycols (PEG 400 and PEG 1000).

Gastrointestinal permeability was compared in seventy-one women, forty-six allergic and twenty-five non-allergic according to case history, by measuring the 6-hr urinary recovery after an oral load of different-sized polyethyleneglycols (PEG 400 and PEG 1000). Further classification, atopic and non-atopic, was obtained by skin-prick tests to inhalant and food allergens in sixty-four of the seventy-one mothers. No significant differences were observed between allergic and non-allergic women, neither regarding the maximum recovery nor the recovery ratio between a large and a small molecule. The results do not lend support to the hypothesis of a persistently increased gut permeability in atopic subjects, which in turn could possibly imply an increased risk of intrauterine sensitization of the foetus of an atopic mother.

Adult↗
PubMed1990

The influence of fixation peg design on the shear stability of prosthetic implants.

The variety of fixation peg designs existing on prosthetic implants indicates uncertainty regarding the optimum design of fixation pegs for the reduction of stress and relative motion at the bone-implant interface. Fixation pegs have a number of important functions on a prosthesis, one of which is to reduce shear stress and shear displacement at the bone-implant interface. This is a parametric study intended to identify trends in the shear stability of prostheses incorporating a range of fixation peg designs. The parameters varied included the number of fixation pegs on a surface, the size of the pegs, and the aspect ratio (length/diameter) of the pegs. Mechanical tests were performed on urethane foam blocks with mechanical properties comparable to trabecular bone. The results indicated the following: (a) Fixation pegs act independently in resisting shearing force if they are spaced sufficiently far apart. (b) For any given shear displacement, smaller pegs generate a greater resistive shear force per unit of peg projected area in the direction of the applied load than larger pegs having the same aspect ratio. (c) Smaller diameter pegs cause the supporting material to yield at lower displacements. (d) Pegs with a high aspect ratio provide high shear stability with a minimum amount of bone removed, but may bend if the aspect ratio becomes excessive. (e) Smaller, slender pegs generate a greater resistive shear force at a given displacement per unit of peg volume than larger, lower aspect ratio pegs.(ABSTRACT TRUNCATED AT 250 WORDS)

Equipment Design↗
PubMed1992

PEG-SOD and myocardial protection. Studies in the blood- and crystalloid-perfused rabbit and rat hearts.

BACKGROUND: Polyethylene glycol, covalently linked to superoxide dismutase (PEG-SOD), has a long plasma half-life (greater than 30 hours) and has been proposed as an effective agent for reducing free radical-mediated injury ischemia and reperfusion. METHODS AND RESULTS: Using an isolated rabbit heart perfused with arterial blood from a support rabbit, we have demonstrated that pretreatment with PEG-SOD (30,000 units/kg, intravenous bolus, 12-24 hours before 60 minutes of normothermic global ischemia), combined with addition of PEG-SOD to the blood perfusion circuit (30,000 units/kg to the support rabbit) and inclusion of PEG-SOD (150 micrograms/ml) in a cardioplegic solution, enhanced the postischemic recovery of left ventricular developed pressure (LVDP) from 51 +/- 6 to 74 +/- 9 mm Hg (p less than 0.05; n = 9 per group). In further studies we showed that, whereas maximum protection was obtained when PEG-SOD was given as a combined pretreatment and additive to both the cardioplegic and the reperfusate solutions (postischemic LVDP recovery increased from 44 +/- 4% in the control group to 70 +/- 3% in the PEG-SOD group), the administration of PEG-SOD during pretreatment plus cardioplegia or during reperfusion alone also resulted in a significant improvement in postischemic function (62 +/- 7% and 60 +/- 3%, respectively). However, the use of PEG-SOD as a cardioplegic additive alone failed to afford protection (47 +/- 4% recovery of LVDP). In dose-response studies (with 0, 3,000, 6,000, 12,000, 30,000, or 60,000 units/kg; n = 8 per group), maximum recovery of LVDP was obtained with the administration of 12,000 units/kg of PEG-SOD. Studies of the plasma activity of PEG-SOD confirmed its long half-life and showed that the treatment with PEG-SOD either 1 hour or 12-24 hours before the study resulted in similar levels of plasma activity. In an attempt to assess any involvement of blood-borne elements in the protection afforded by PEG-SOD, studies were also carried out in the crystalloid-perfused rabbit heart, and no protection was observed. Similarly, no protection was observed at any one of a variety of doses in the crystalloid-perfused rat heart. CONCLUSIONS: PEG-SOD can afford protection in the blood-perfused rabbit heart; this protection is dose dependent and probably involves some action of PEG-SOD on blood-borne elements, possibly leukocytes.

Animals↗
PubMed1990

Repeat percutaneous endoscopic gastrostomy (PEG): an outpatient procedure.

Patients who have previously undergone percutaneous endoscopic gastrostomy (PEG) with subsequent PEG removal occasionally require elective repeat PEG. Adhesion of the stomach to the abdominal wall after the original PEG allows repeat PEG to be performed as an outpatient procedure and full-volume tube feeding to be started immediately. Elective repeat PEG was performed in ten patients. Repeat PEG was performed at the site of the original PEG in all cases. Six of the ten repeat PEGs were performed as an outpatient procedure. No complications were attributed to repeat PEG, and full-volume tube feedings were tolerated in all cases when attempted. To obviate the need for repeat PEG, we recommend immediate replacement after inadvertent PEG removal and avoiding elective removal of PEGs used in patients with long-term neurologic impairment for at least 6 months.

Ambulatory Surgical Procedures↗
PubMed1992

The uses and properties of PEG-linked proteins.

Poly(ethylene glycol) (PEG) is a water soluble polymer that when covalently linked to proteins, alters their properties in ways that extend their potential uses. PEG-modified conjugates are being exploited in many different fields. The improved pharmacological performance of PEG-proteins when compared with their unmodified counterparts prompted the development of this type of conjugate as a therapeutic agent. Enzyme deficiencies for which therapy with the native enzyme was inefficient (due to rapid clearance and/or immunological reactions) can now be treated with equivalent PEG-enzymes. PEG-adenosine deaminase has already obtained FDA approval. PEG-modified cytokines have been constructed and, interestingly, one of the conjugates, PEG-modified granulocyte-macrophage colony-stimulating factor, showed dissociation of two biological properties. This novel observation may open new horizons to the application of PEGylation technology. The biotechnology industry has also found PEG-proteins very useful because PEG-enzymes can act as catalysts in organic solvents, thereby opening the possibility of producing desired stereoisomers, as opposed to the racemic mixture usually obtained in classical organic synthesis. Covalent attachment of PEG to proteins requires activation of the hydroxyl terminal group of the polymer with a suitable leaving group that can be displaced by nucleophilic attack of the epsilon-amino terminal of lysine residues (other nucleophilic groups can also interact). Several chemical groups have been exploited to activate PEG, thereby giving rise to a variety of PEG-proteins. Some of these varieties retain part of the activating group as a coupling moiety between PEG and protein and others provide a direct linkage. For each particular application, different coupling methods provide distinct advantages.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Polyethylene glycol (PEG) modification of granulocyte-macrophage colony stimulating factor (GM-CSF) enhances neutrophil priming activity but not colony stimulating activity.

PEG-modified proteins have numerous advantages over their unmodified counterparts (increased half life, reduced antigenicity, improved solubility), but almost without exception, they show a modest to marked reduction in biological or enzymatic activity. However, while investigating a new protocol for the preparation of PEG-proteins, we compared PEG-modified and unmodified GM-CSF with respect to their polymorphonuclear neutrophil granulocyte (PMN) priming activities. PEG-GM-CSF was unexpectedly more active than GM-CSF in its ability to prime neutrophils to respond to the synthetic peptide n-formyl-methionyl-leucyl-phenylalanine (FMLP) with an oxidative burst (assessed both by nitroblue tetrazolium reduction and ferricytochrome c reduction). These results were in contrast to the findings for colony stimulating activity and with GM-CSF induced thymidine uptake, where the biological activity was unchanged or reduced. The enhanced neutrophil priming activity of PEG-GM-CSF was confirmed using FPLC fractionated PEG-modified GM-CSF. This showed changes in the bioactivity profile consistent with both the shift in protein elution profile and enhanced activity of the PEG-modified material (reflected in the increased area under the bioactivity curve). We also excluded a neutrophil priming action for PEG-modified fetal calf serum proteins, carrier proteins and 'irrelevant' cytokine, erythropoietin. The dissociation of the two bioactivities was confirmed using individual FPLC fractions. These results suggest the presence of differences in either binding, receptor/ligand processing or signal transduction for neutrophils versus progenitors, that are differentially affected by PEG-modification of GM-CSF. The demonstration that PEG-modification can partially dissociate two biological activities suggests the feasibility of using PEG-modification to produce proteins with subtly altered spectra of biological activity and hence new ranges of clinical applications.

Cells, Cultured↗