Polymers Of Ethylene Glycol Research Articles

A comparison of ion channel current blockades caused by individual poly(ethylene glycol) molecules and polyoxometalate nanoclusters.

Proteinaceous nanometer-scale pores have been used to detect and physically characterize many different types of analytes at the single-molecule limit. The method is based on the ability to measure the transient reduction in the ionic channel conductance caused by molecules that partition into the pore. The distribution of blockade depth amplitudes and residence times of the analytes in the pore are used to physically and chemically characterize them. Here we compare the current blockade events caused by flexible linear polymers of ethylene glycol (PEGs) and structurally well-defined tungsten polyoxymetallate nanoparticles in the nanopores formed by Staphylococcus aureusα-hemolysin and Aeromonas hydrophila aerolysin. Surprisingly, the variance in the ionic current blockade depth values for the relatively rigid metallic nanoparticles is much greater than that for the flexible PEGs, possibly because of multiple charged states of the polyoxymetallate clusters.

Тhe Viscosity Study of Naftifine Hydrochloride Solution with a Combination of Polyethylene Glycols

Introduction. Naftifin hydrochloride is an antifungal drug from the allylamine group, which is used as a drug for external use in the treatment of onychomycosis. Quickly penetrates the skin and nails. It has antifungal, antibacterial and anti-inflammatory effects. It has a wide range of actions against many fungi that cause onychomycosis (dermatophytes, molds and yeast). In addition, it has an antibacterial effect in the ratio of gram-positive and gram-negative bacteria, reduces the risk of complicated course of the disease. It has a pronounced anti-inflammatory effect. Polyethylene glycols belong to the class of organic polymers of ethylene glycol. Polyethylene glycols are safe and widely used in pharmaceutical production, due to the variety of applications. The object of the study is a number of solutions of naftifin hydrochloride in different combinations and with different ratios of polyethylene glycols.Aim. The purpose of the work is to choose the optimal composition of the solution of naftifin hydrochloride. Achieve due to the viscosity of the prolonging action of the solution. Depending on the molecular weight of polyethylene glycol to determine the flow time of solutions. Choose among a number of samples with different ratios of polyethylene glycols, a solution with maximum viscosity.Materials and methods. To determine the viscosity of this solution, a capillary viscometry method was used on the vpzh-2 apparatus. «Exoderil» solution was chosen as a reference formulation.Results and discussion. Alternating different combinations of polyethylene glycol, we have increased the viscosity of the fluid naftifine hydrochloride, which has achieved a more accurate method of application of medicinal substances. During the study, it was determined that the solution «Exoderil» has a minimum viscosity, compared with all samples of the studied solutions.Сonclusion. The optimal viscosity of the solution of naftifin hydrochloride provides a prolonged action of the drug, due to a longer stay on the nail plate. Viscosity allows for more accurate application to the damaged nail, and reduces the loss of concentration of the active substance. Moisturizing properties of polyethylene glycols will help to reduce the severity of side effects (dryness, rarefaction), and provide a longer and more comfortable treatment of onychomycosis.

Macrogol hypersensitivity reactions during cleansing preparation for colon endoscopy

Macrogols are polymers of ethylene glycol (PEG) that are widely used as laxatives (higher-weight variants) or as excipients in pharmaceutical products (lower-weight variants), for example, as solvents in oral liquids and soft capsules. In colon endoscopy or surgery and in radiologic examinations of the large and small intestines, macrogols are used as osmotic laxatives to minimize fecal contamination. Generally, PEG preparations are well tolerated and safe, although the National Patient Safety Agency1 issued a report that alerted health care providers to the potential risk of adverse reaction to all oral bowel-cleansing preparations.

Pegylated Interferon-ALFA-2A (PEG-IFN-α-2A; PEGASYS) Therapy Renders High Clinical and Molecular Response Rates in Patients with Essential Thrombocythemia (ET) and Polycythemia VERA (PV)

Patients with high-risk essential thrombocythemia (ET) and polycythemia vera (PV) are typically managed with cytoreductive agents such as recombinant interferon-alpha (IFN-α), hydroxyurea (HU), and anagrelide (AG). Despite the significant activity of IFN-α in ET and PV, this agent is frequently hindered by poor tolerance and inconvenient dosing schedules. PEG-IFN-α is formulated by covalently attaching polymers of ethylene glycol to the native IFN-α molecule, resulting in decreased renal excretion and increased serum half-life that allows for weekly administration. On this basis, we are conducting a phase II study of subcutaneous PEG-IFN-α-2a (Pegasys) for patients with ET or PV. A total of 76 patients have been enrolled and treated thus far (36 ET, 40 PV). Median age is 53 years (range, 18–77), time from diagnosis to PEG-IFN-α-2a 49 months (range, 0–355), WBC count 8.7×109/L (range, 3.7–27.8), hemoglobin 13.5 g/dL (range, 8.9–18.8), and platelet count 554×109/L (range, 140–1641). Prior therapies (median 1; range 0–6) included HU (n=44), AG (n=29), IFN-α (n=11: 5 oral and 6 sc), imatinib (n=7), and dasatinib (n=1). PEG-IFN-α-2a was the initial therapy in 13 patients that refused therapy with HU. The JAK2 V617F mutation was detected in 20 (56%) of 36 ET and in 37 (92.5%) of 40 PV patients. Nine (12%) patients had abnormal cytogenetics. Initial starting dose of PEG-IFN-α-2a was 450 mcg/week, but that was modified to the current starting dose of 90 mcg/week. Dose modifications are allowed according to response or toxicity. Patients are currently receiving 450 mcg (n=1), 270 mcg (n=3), 180 mcg (n=14), 135 mcg (n=8), 90 mcg (n=27), and 45 mcg (n=7). After a median follow-up of 23 months (range, 2–38), 63 (85%) of 74 assessable patients have responded. The median time to response was 4 weeks (range, 0.5–26). Complete response (CR) was achieved by 60 (81%) patients (for ET: platelets <440×109/L, off HU and AG, in the absence of thromboembolic events; for PV: Hb <15 g/dL, off HU and AG, no phlebotomy, with disappearance of splenomegaly) whereas 3 (4%) patients (1 PV, 2 ET) had a partial response ([PR]; no phlebotomy, off HU and AG, but still palpable spleen). Of 5 assessable patients with abnormal karyotype at the start of the study, 2 reverted to diploid cytogenetics. The mutant JAK2 V617F to total JAK2 ratio was determined by quantitative pyrosequencing assay in all 76 patients prior to PEG-IFN-α-2a and was repeated at least once during therapy in 41 JAK2 V617F-positive patients. Overall, 23 (56%) had >10% reduction in JAK2 V617F expression, including 14 (34%) who had a >50% reduction. In 5 (11%) of the latter the mutant allele became undetectable. PEG-IFN-α-2a was well tolerated in most patients. Thirty-nine episodes of grade 3–4 toxicity were reported: neutropenia (n=15), elevated transaminases (n=5), infection (n=4), fatigue (n=3), pain (n=3), cardiac (n=2), and anemia, thrombocytopenia, depression, shortness of breath, pruritus, thrombosis, and dizziness in 1 case each. Sixteen (21%) patients were taken off study after a median of 8 months (range, 2–26) on PEG-IFN-α-2a but only 7 (9%) of them due to due to therapy-related toxicities: grade 3 neutropenia, anorexia, depression, ischemic retinopathy, dyspnea, confusion, and pruritic rash. In conclusion, PEG-IFN-α-2a therapy results in remarkable clinical activity with an acceptable toxicity profile in advanced, previously treated, patients with ET or PV. Clinical responses are frequently accompanied by significant reduction of JAK2 V617F allele burden, which becomes undetectable in a proportion of them, suggesting selective targeting of the malignant clone.

Hybrydowe uklady typu polimer hydrofilowy/montmorylonit

A literature review on hybrid systems consisted of hydrophilic polymer (cationic, anionic or nonionic one) and montmorillonite (MMT, Fig. 1 and 2) is presented. The methods of preparation, evaluation and applications directions are discussed. Preparation of such products let modify the functional properties of polymers. The hybrid systems based on polyacrylamide (PAAm) (Fig. 3-5), acrylamide copolymers, polyvinylpyrrolidone (PVP), poly(acrylic acid) (PAA) (Fig. 6), poly(ethylene oxide) (PEO), oligomers or polymers of ethylene glycol (Fig. 7) or polymer of natural origin - starch, containing montmorillonite were characterized in detail.

Pegylated Interferon-alfa-2a (PEG-IFN-α-2A; PEGASYS™) for Essential Thrombocythemia (ET) and Polycythemia Vera (PV): An Update of an Ongoing Phase II Study.

Therapy for patients with high-risk Philadelphia chromosome-negative myeloproliferative disorders (MPDs) involves the use of cytoreductive agents such as recombinant human interferon-alpha (IFN-α), hydroxyurea (HU), and anagrelide (AG). Despite the significant activity of IFN-α in MPDs, therapy with this agent is frequently hindered by poor tolerance and inconvenient dosing schedules. PEG-IFN-α is formulated by covalently attaching polymers of ethylene glycol to the native IFN-α molecule, which results in decreased renal excretion and increased serum half-life that allows for weekly administration with acceptable toxicity. Based on the superior pharmacokinetic profile of PEG-IFN-α-2a relative to conventional IFN-α, we designed a phase II study of subcutaneous PEG-IFN-α-2a (Pegasys) for patients with ET or PV. A total of 50 patients have been enrolled and treated thus far (22 ET, 28 PV). Median age is 53 years (range, 23–77) and time from diagnosis to PEG-IFN-α-2a 64 months (range, 1–348). Prior therapies (median 2; range 0–6) included HU (n=33), AN (n=22), phlebotomy (n=27), IFN-α (n=8: 5 oral and 3 sc), other (n=10). PEG-IFN-α-2a was the initial therapy in 4 patients. The JAK2 V617F mutation was detected in 11 (50%) of 22 ET and in 26 (93%) of 28 PV patients. Six (12%) patients had abnormal cytogenetics. Initial starting dose of PEG-IFN-α-2a was 450 mcg/week, but that was modified to the current starting dose of 90 mcg/week. Dose modifications are allowed according to response or toxicity. Patients are currently receiving 450 mcg (n=1), 360 mcg (n=1), 270 mcg (n=5), 180 mcg (n=11), 135 mcg (n=8), 90 mcg (n=9), and 45 mcg (n=5). After a median follow-up of 11 months (range, 2–28), 47 (94%) patients have responded. Complete response (CR) was achieved by 46 (92%) patients (for ET: platelets <440x109/L, off HU and AG, in the absence of thromboembolic events; for PV: Hb <15 g/dL, off HU and AG, no phlebotomy, with disappearance of splenomegaly) whereas 1 (2%) patient with PV had a partial response ([PR]; no phlebotomy, off HU and AG, but still palpable spleen). The mutant JAK2 V617F to total JAK2 ratio was determined by PCR (n=37) and by a quantitative pyrosequencing assay (n=30) prior to PEG-IFN-α-2a. JAK2 V617F mutational analysis was subsequently performed after 6 and 12 months into PEG-IFN-α-2a therapy in 20 and 10 patients, respectively. Nine (30%) of the 30 patients assessable for JAK2 V617V quantitation had >10% reduction in JAK2 V617F expression, including 2 (7%) in whom the mutant allele became undetectable. In addition, 4 (13%) patients had a 5%–10% reduction. JAK2 V617F quantitation has not been repeated yet in 9 patients. PEG-IFN-α-2a was well tolerated in most patients. Twenty-two episodes of grade 3–4 toxicity were reported, including neutropenia (n=11), elevated transaminases (n=4), and anemia, thrombocytopenia, depression, fatigue, infection, cardiac, and pain in 1 case each. Ten patients were taken off study, including 6 (12%) due to therapy-related toxicities: grade 3 neutropenia (n=1), fatigue (n=1), depression (n=1), ischemic retinopathy (n=1), dyspnea (n=1),and diarrhea (n=1). In summary, therapy with PEG-IFN-α-2a results in remarkable clinical activity and acceptable toxicity profile in patients with ET or PV. Significant reduction of JAK2 V617F allele burden occurred in a proportion of responders, suggesting selective targeting of the malignant clone.

Treatment with Pegylated Interferon-Alfa-2A (PEG-IFN-α-2A; PEGASYS™) for Patients with Essential Thrombocythemia (ET) and Polycythemia Vera (PV).

Patients (pts) with high-risk Philadelphia chromosome-negative myeloproliferative disorders (MPDs) are customarily treated with cytoreductive agents such as recombinant human interferon-alpha (IFN-α), hydroxyurea (HU), and anagrelide (AG). Despite the significant activity of IFN-α in MPDs, responses have been frequently limited by poor tolerance and inconvenient dosing schedules. PEG-IFN-α is formulated by covalently attaching polymers of ethylene glycol to the native IFN-α molecule, which results in increased serum half-life, decreased renal excretion, thus allowing for weekly administration while maintaining acceptable toxicity profile. Based on the superior pharmacokinetic and pharmacodynamic profile of PEG-IFN-α relative to IFN-α we designed a phase II study of subcutaneous (sc) PEG-IFN-α-2a (Pegasys™) for pts with ET and PV. A total of 23 pts have been enrolled so far (13 ET, 10 PV). First 3 pts received PEG-IFN-α-2a at 450mcg weekly but experienced toxicity and had to reduce the dose; next 3 pts started at 360mcg weekly and again had to reduce the dose due to toxicity; last 17 pts started at 270mcg weekly and tolerated therapy well. Dose modifications of 90 mcg are allowed according to response or toxicity. Median age is 54 years (range, 23 to 73), time from diagnosis to PEG-IFN-α-2a therapy 64 months (range, 1 to 282), Hb 13.5 g/dL (range, 8.9 to 18.5), WBC 5×109/L, (range, 4.3 to 49), platelets 592×109/L (range, 298 to 1000). All pts had prior therapies (median 2, range 1–6), including HU (n=17), AG (n=13), IFN-α (n=6: 4 oral and 2 sc), imatinib mesylate (n=2) and others (n=3). In addition, 8 PV pts had received phlebotomies. The JAK2 V617F mutation was detected in 6 (46%) of 13 ET pts and in 9 (90%) of 10 PV pts. All pts had diploid cytogenetics. After a median follow-up of 6 months (range, 1 to 15), 11 of 13 (85%) ET pts have achieved a complete response (platelets <440×109/L, off HU and AG, in the absence of thromboembolic events); 2 pts without response received less than 2 months of therapy so far. Six of 10 (60%) PV pts achieved complete remission (Hb <15 g/dL, off HU and AG, no phlebotomy, with disappearance of splenomegaly), 3 (30%) achieved partial response (no phlebotomy, off HU and AG, but still palpable spleen), and 1 have not responded so far (less than 3 months on the therapy), for overall response of 90%. The median time to response was 1.5 months (range, 0.5 to 5.6). While the first 6 pts on the study, that received high PEG-IFN-α-2a dose (450 or 360mcg weekly), experienced grade 3 toxicity, among last 17 pts that received 270mcg weekly, there were only 5 cases of grade 3 toxicity (anemia, increased liver function tests, and neutropenia x3) requiring dose reduction. However, to preserve pts quality of life, the dose of PEG-IFN-α-2a was also reduced for the persistent grade 2 toxicity (> 2 weeks). Overall, 17 pts (74%) reduced the dose so far, while 6 pts (all on 270mcg weekly) remain at the same initial dose. Only 2 pts (1 ET, 1 PV) discontinued therapy, due to retinal infiltrates and depression after 8 and 6 months on therapy, respectively. In summary, therapy with PEG-IFN-α-2a has an acceptable toxicity profile and significant activity in pts with ET and PV. Updated clinical and molecular results will be presented.

Pegylated Interferon Therapy for Patients with Philadelphia Chromosome-Negative Myeloproliferative Disorders

The conventional management of patients with high-risk Philadelphia chromosome-negative (Ph-negative) myeloproliferative disorders (MPDs) revolves around the administration of cytoreductive agents such as hydroxyurea, anagrelide, and recombinant human interferon alpha (IFN-alpha). IFN-alpha has shown significant activity in the treatment of chronic myelogenous leukemia (CML) and Ph-negative MDPs. However, the response rates of IFN-alpha therapy frequently have been hampered by high dropout rates due to side effects and inconvenient dosing schedules. Pegylated (PEG) IFN-alpha is formulated by covalently attaching polymers of ethylene glycol of large molecular weight to the native IFN-alpha molecule. Such chemical modification increases serum half-life, decreases renal excretion, and results in prolonged patient exposure to PEG-IFN-alpha, thus allowing for weekly administration while maintaining acceptable toxicity, tolerability, and activity profiles. The lack of adequate therapies for patients with MPDs and the superior pharmacokinetic and pharmacodynamic profile of PEG-IFN-alpha relative to standard IFN-alpha has prompted the investigation of the activity and safety of PEG-IFN-alpha in patients with essential thrombocythemia, polycythemia vera, and idiopathic myelofibrosis. We summarize the available data on the use of PEG-IFN-alpha in patients with Ph-negative MPDs.

Special Report: Reproductive and Developmental Toxicity of Ethylene Glycol and Its Ethers

Polymers of Ethylene Glycol are linked via ether linkages with various alcohols or via ester linkages to various fatty acids in many cosmetic ingredients. Ethylene Glycol, when reacted with an alkyl alcohol, forms an ethylene glycol monoalkyl ether. These compounds are metabolized in the human body by alcohol dehydrogenase and aldehyde dehydrogenase to form corresponding acetaldehyde and acetic acid derivatives. Data are presented that show reproductive and developmental toxicity is associated with metabolites of ethylene glycol monoalkyl ethers, but not with the monoalkyl ethers themselves. Further, it is suggested that the toxicity of these metabolites is inversely proportional to the length of the alkyl chain in the original alkyl ether. In the case of the compounds used in cosmetics, most have alcohols or fatty acids linked to polyethylene glycol chains, not a single Ethylene Glycol moiety. Where Ethylene Glycol is linked to a fatty acid by an ester linkage, the resulting compound is chemically different from the monoalkyl ethers. Where Ethylene Glycol is linked to an alcohol via an ether linkage, the alkyl chain is large and complex, suggesting little or no potential toxicity. Overall, it was found that metabolites of ethylene glycol monoalkyl ethers are reproductive and developmental toxins. In general, however, the metabolites of concern are not expected to be formed in cosmetic formulations that contain polymers of ethylene glycol.

The charge state of an ion channel controls neutral polymer entry into its pore.

Electrostatic potentials created by fixed or induced charges regulate many cellular phenomena including the rate of ion transport through proteinaceous ion channels. Nanometer-scale pores of these channels also play a critical role in the transport of charged and neutral macromolecules. We demonstrate here that, surprisingly, changing the charge state of a channel markedly alters the ability of nonelectrolyte polymers to enter the channel's pore. Specifically, we show that the partitioning of differently-sized linear nonelectrolyte polymers of ethylene glycol into the Staphylococcus aureus alpha-hemolysin channel is altered by the solution pH. Protonating some of the channel side chains decreases the characteristic polymer size (molecular weight) that can enter the pore by approximately 25% but increases the ionic current by approximately 15%. Thus, the "steric" and "electric" size of the channel change in opposite directions. The results suggest that effects due to polymer and channel hydration are crucial for polymer transport through such pores.

Contribution of water to free energy of hydrolysis of pyrophosphate.

The energy of hydrolysis of phosphate compounds varies depending on whether they are in solution or bound to the catalytic site of enzymes. With the purpose of simulating the conditions at the catalytic site, the observed equilibrium constant for pyrophosphate hydrolysis (Kobsd) was measured in aqueous mixtures of dimethyl sulfoxide, ethylene glycol, or polymers of ethylene glycol. The reaction was catalyzed by yeast inorganic pyrophosphatase at 30 degrees C. All the cosolvents used promoted a decrease of Kobsd. Polymers of ethylene glycol were more effective than dimethyl sulfoxide or ethylene glycol in decreasing Kobsd. The higher the molecular weight of the polymer, the lower the value of Kobsd. A decrease in Kobsd from 346 M (delta G degree obsd = -3.5 kcal mol-1) to 0.1 M (delta G degree obsd = 1.3 kcal mol-1) was observed after the addition of 50% (w/v) poly(ethylene glycol) 8000 to a solution containing 0.9 mM MgCl2 and 1 mM Pi at pH 8.0. The association constants of Pi and pyrophosphate for H+ and Mg2+ were measured in presence of different ethylene glycol concentrations in order to calculate the Keq for hydrolysis of different ionic species of pyrophosphate. A decrease in all the Keq was observed. The results are interpreted according to the concept that the energy of hydrolysis of phosphate compounds depends on the different solvation energies of reactants and products.

Electron spin resonance study on the mechanism of polyethylene glycol—membrane interaction

There is a growing interest in the application of cell fusion in various fields of modern bioiogy. Besides viruses, some chemicals are also effective in causing biological membranes to fuse. Among the most potent fusogens of this type appear to be polymers of ethylene glycol. Polyethylene glycol (PEG) has been used to fuse a great variety of cell types [l-3]. The wide applications of PEG-induced cell fusion stimulate research on the mechanism by which the polymer interacts with biological membranes. Most of the studies performed have been focussed on the effect of PEG on the organization of membrane phospholipids [4131. The molecular mechanism of PEG-membrane interaction and the sequence of events leading to cell fusion remain, however, not fully understood. Particularly little is known about the effect of PEG on the physica state of membrane proteins. Spin labels used in this study, 2,2,6,6-tetramethyl-4-maleimidopiperidine-I-oxyl (MSL) and 5-doxylstearic acid, were obtained from Syva (Palo Alto CA). Chromatographically pure egg yolk phosphatidylcholine and cholesterol were from Sigma (St Louis MO). Polyethylene glycol A4,6000 (PEG 6000) was supplied by Loba (Vienna). Human erythrocyte ghost membranes were prepared as in [14]. Protein spin-labeling with MSL and lipid spin-labeling with S-doxylstearic acid were performed as in [15].

Polyethylene glycol in aqueous solution: Solvent perturbation and gel filtration studies

As part of an investigation of the mechanism of precipitation of proteins by synthetic polymers, we measured the ability of oligomers and polymers of ethylene glycol to (a) alter the solubility of amino acids, (b) perturb the absorption spectra of aromatic amino acids, and (c) enhance the fluorescence of 1,8-anilinonaphthalene sulfonate (ANS). All of these effects increased with increasing degree of polymerization, up to a molecular weight of about 400. This trend can be partially attributed to the diminishing influence of the terminal OH groups. However, small analogs such as dioxane and dimethoxyethane (lacking OH groups) were much less effective than the polymers, suggesting a cooperative effect between neighboring ethoxide residues in the polymer. In contrast, the effectiveness of polyethylene glycol (PEG) as a protein-precipitating agent continued to increase with increasing size; polymers of molecular weight 4000–6000 were substantially more effective than their 10-fold smaller homologues. On exclusion chromatographic columns, the synthetic polymers eluted much earlier than did proteins of comparable molecular weight. This discrepancy diminished in 6 m guanidine where the proteins eluted much earlier, reflecting their conversion to random coils. In contrast, the elution of PEG was only slightly affected, suggesting a random coil configuration even in the absence of denaturant. PEG-20M, a mixture prepared by coupling 2 mol of PEG-6000 with an epoxide, was resolved into two components by exclusion chromatography on Sephadex G-100. The fast-eluting component (the coupled product) was unusually effective in enhancing ANS fluorescence and was shown to bind the dye with K a = 5.1 × 10 3, M −1 at 25 °C.

Time and mode of fusion of human fibroblasts treated with polyethylene glycol (PEG)

SOMATIC cell fusion has become a powerful tool in cell biology and genetics1–3 Until recently the standard reagent for increasing the rate of fusion in cultures of animal cells was inactivated Sendai virus4. In 1974 polymers of ethylene glycol (polyethylene glycol, PEG), over a wide range of molecular weights, were shown to be very effective, non-toxic chemical ‘fusogens’ for higher plant protoplasts5. They were then applied to fuse hen erythrocytes6 and these with yeast protoplasts7. Applied to mammalian, including human, cultured somatic cells they yielded hybrid cells capable of indefinite multiplication8,9. Applied to somatic cell protoplasts of two species of higher plants, they yielded hybrid protoplasts which regenerated, multiplied and developed into whole hybrid plants10. The list of cells and cell organelles fused has now expanded to include bacterial and fungal protoplasts and chloroplasts. It is reasonable to expect that PEG will induce the fusion of almost any two biological membranes and become an increasingly useful tool in their investigation6,11.

Relationship between membrane function and permeability. 3. Further evidence linking membrane transport and thromboplastin availability of the intact erythrocyte.

Summary Within a series of short straight‐chain compounds resembling glycerol in structure, the pattern of unmasking of erythrocyte ‘platelet factor 3’ (PF‐3) activity appeared to be related to a combination of cell penetrability, molecular weight and complement of hydroxyl groups. The same relationship held in a series of low molecular weight polymers of ethylene glycol. Moreover, propylene glycol and ethylene glycol monomethylether, at very low concentrations, were shown to delay glycerol‐induced erythrocyte PF‐3 enhancement. Among penetrating non‐electrolytes not having a structural similarity to glycerol, dimethylsulphoxide was the only compound that had a family of PF‐3 enhancement curves of the glycerol type.The glycerol induced PF‐3 enhancement curves with cow and sheep erythrocytes were similar to those of erythritol with human erythrocytes. Furthermore, the attainment of equilibrium of 14C erythritol between human erythrocyte and plasma compartments correlated temporally with unmasking of PF‐3 activity by erythritol solutions.The discussion attempts to relate these findings to new theoretical views which emphasize a close link between membrane transport and thromboplastin availability in the intact erythrocyte.