Size fractionation of double-stranded DNA by precipitation with polyethylene glycol

PubMed Central

Lis, John T.; Schleif, Robert

1975-01-01

We show that DNA molecules of differing molecular mass are separable by selective precipitation with polyethylene glycol (PEG†). Higher molecular mass DNA precipitates at lower PEG concentrations than lower molecular mass DNA. Double-stranded DNA can be fractionated at least in the range of 3 × 107 to 1 × 105 daltons. The effects of PEG concentration, sodium chloride concentration, DNA concentration, pH, divalent ions, precipitation time, and centrifugal force have been determined. These studies show PEG precipitation offers a size fractionation method for DNA which is convenient, of high capacity, and applicable over a wide range of conditions. However, resolution is not high and separation of two species approaches 100% only if they differ in molecular mass by at least a factor of two. Images PMID:236548

Coating solid dispersions on microneedles via a molten dip coating method: development and in vitro evaluation for transdermal delivery of a water insoluble drug

PubMed Central

Ma, Yunzhe; Gill, Harvinder S.

2014-01-01

This study demonstrates for the first time the ability to coat solid dispersions on microneedles as a means to deliver water-insoluble drugs through the skin. Polyethylene glycol (PEG) was selected as the hydrophilic matrix, and lidocaine base was selected as the model hydrophobic drug to create the solid dispersion. First, thermal characterization and viscosity measurements of the PEG-lidocaine mixture at different mass fractions were performed. The results show that lidocaine can remain stable at temperatures up to ~130 °C, and that viscosity of the PEG-lidocaine molten solution increases as the mass fraction of lidocaine decreases. Differential scanning calorimetry demonstrated that at lidocaine mass fraction less than or equal to 50%, lidocaine is well dispersed in the PEG-lidocaine mixture. Uniform coatings were obtained on microneedle surfaces. In vitro dissolution studies in porcine skin showed that microneedles coated with PEG-lidocaine dispersions resulted in significantly higher delivery of lidocaine in just 3 min compared to 1 h topical application of 0.15 g EMLA®, a commercial lidocaine-prilocaine cream. In conclusion, the molten coating process we introduce here offers a practical approach to coat water-insoluble drugs on microneedles for transdermal delivery. PMID:25213295

Effects of PEG4000 template on sol-gel synthesis of porous cerium titanate photocatalyst

NASA Astrophysics Data System (ADS)

Zhang, Wenjie; Tao, Yingjie; Li, Chuanguo

2018-04-01

Porous cerium titanate was synthesized by sol-gel method, using polyethylene glycol (PEG4000) as template agent. Brannerite structured CeTi2O6 in monoclinic system is the major substance formed in the materials. Formation of CeO2 and rutile TiO2 depends on the amount of PEG4000. The addition of PEG4000 leads to production of fine particles in the samples, but it does not apparently affect the band gap energy. Pore volume of the cerium titanate sample continuously increases with rising PEG4000 amount. The sample obtained using 3.5 g PEG4000 has BET surface area of 16.2 m2/g and pore volume of 0.0232 cm3/g. The addition of PEG4000 can obviously promote photocatalytic activity of cerium titanate, which can be proven by both enhanced production of hydroxyl radical and ofloxacin degradation efficiency. As much as 95.2% of the initial ofloxacin molecules are removed from the solution after 50 min of photocatalytic degradation on the cerium titanate obtained using 3.5 g PEG4000, while only 48.4% ofloxacin is removed on cerium titanate obtained without PEG4000.

Measuring intestinal fluid transport in vitro: Gravimetric method versus non-absorbable marker.

PubMed

Whittamore, Jonathan M; Genz, Janet; Grosell, Martin; Wilson, Rod W

2016-04-01

The gut sac is a long-standing, widely used in vitro preparation for studying solute and water transport, and calculation of these fluxes requires an accurate assessment of volume. This is commonly determined gravimetrically by measuring the change in mass over time. While convenient this likely under-estimates actual net water flux (Jv) due to tissue edema. We evaluated whether the popular in vivo volume marker [(14)C]-PEG 4000, offers a more representative measure of Jvin vitro. We directly compared these two methods in five teleost species (toadfish, flounder, rainbow trout, killifish and tilapia). Net fluid absorption by the toadfish intestine based on PEG was significantly higher, by almost 4-fold, compared to gravimetric measurements, compatible with the latter under-estimating Jv. Despite this, PEG proved inconsistent for all of the other species frequently resulting in calculation of net secretion, in contrast to absorption seen gravimetrically. Such poor parallelism could not be explained by the absorption of [(14)C]-PEG (typically <1%). We identified a number of factors impacting the effectiveness of PEG. One was adsorption to the surface of sample tubes. While it was possible to circumvent this using unlabelled PEG 4000, this had a deleterious effect on PEG-based Jv. We also found sequestration of PEG within the intestinal mucus. In conclusion, the short-comings associated with the accurate representation of Jv by gut sac preparations are not overcome by [(14)C]-PEG. The gravimetric method therefore remains the most reliable measure of Jv and we urge caution in the use of PEG as a volume marker. Copyright © 2016 Elsevier Inc. All rights reserved.

Lipolysis of the semi-solid self-emulsifying excipient Gelucire 44/14 by digestive lipases.

PubMed

Fernandez, Sylvie; Rodier, Jean-David; Ritter, Nicolas; Mahler, Bruno; Demarne, Frédéric; Carrière, Frédéric; Jannin, Vincent

2008-08-01

Gelucire 44/14 is a semi-solid self-emulsifying excipient used for the oral delivery of poorly water-soluble drugs. It is composed of C8-C18 acylglycerols and PEG-32 esters, all of which are potential substrates for digestive lipases. Here we studied the lipolysis of Gelucire 44/14 by porcine pancreatic extracts, human pancreatic juice and several purified digestive lipases. Human pancreatic lipase (HPL), the main lipase involved in the digestion of triacylglycerols, did not show any significant activity on Gelucire 44/14 or on either of its individual compounds, C8-C18 acylglycerols and PEG-32 esters. Other pancreatic lipases such as human pancreatic lipase-related protein 2 (HPLRP2) showed low activity on Gelucire 44/14 although the highest activity of HPLRP2 was that observed on the C8-C18 acylglycerol fraction, which accounts for 20% (w/w) of Gelucire 44/14. In addition, HPLRP2 showed low activities on the PEG-32 esters, whether these were tested individually or mixed together. Carboxyl ester hydrolase (CEH) showed high activity on Gelucire 44/14, and the highest activities of CEH were those recorded on the total PEG-32 ester fraction and on each individual PEG-32 ester, except for PEG-32 monostearate. The highest activity of all the enzymes tested was that of dog gastric lipase (DGL) on Gelucire 44/14, although DGL showed low activity on the PEG-32 ester fraction and on each individual PEG-32 ester. We compared the lipolysis of Gelucire 44/14 with that of Labrasol, another self-emulsifying excipient, which is liquid at room temperature. Human pancreatic juice showed similar rates of activity on both Gelucire 44/14 and Labrasol. This finding means that these excipients are hydrolyzed in vivo during pancreatic digestion, mainly by CEH in the case of Gelucire 44/14 and by both HPLRP2 and CEH in that of Labrasol, whereas HPL showed very low activities on each of these two excipients. This is the first time the effects of PEG and acyl chain length on the lipolytic activity of digestive lipases on PEG esters have been investigated.

Microstructural effects in drug release by solid and cellular polymeric dosage forms: A comparative study.

PubMed

Blaesi, Aron H; Saka, Nannaji

2017-11-01

In recent studies, we have introduced melt-processed polymeric cellular dosage forms to achieve both immediate drug release and predictable manufacture. Dosage forms ranging from minimally-porous solids to highly porous, open-cell and thin-walled structures were prepared, and the drug release characteristics investigated as the volume fraction of cells and the excipient molecular weight were varied. In the present study, both minimally-porous solid and cellular dosage forms consisting of various weight fractions of Acetaminophen drug and polyethylene glycol (PEG) excipient are prepared and analyzed. Microstructures of the solid forms and the cell walls range from single-phase solid solutions of the excipient and a small amount of drug molecules to two-phase composites of the excipient and tightly packed drug particles. Results of dissolution experiments show that the minimally-porous solid forms disintegrate and release drug by slow surface erosion. The erosion rate decreases as the drug weight fraction is increased. By contrast, the open-cell structures disintegrate rapidly by viscous exfoliation, and the disintegration time is independent of drug weight fraction. Drug release models suggest that the solid forms erode by convective mass transfer of the faster-eroding excipient if the drug volume fraction is small. At larger drug volume fractions, however, the slower-eroding drug particles hinder access of the free-flowing fluid to the excipient, thus slowing down erosion of the composite. Conversely, the disintegration rate of the cellular forms is limited by diffusion of the dissolution fluid into the excipient phase of the thin cell walls. Because the wall thickness is of the order of the drug particle size, and the particles are enveloped by the excipient during melt-processing, the drug particles cannot hinder diffusion through the excipient across the walls. Thus the disintegration time of the cellular forms is mostly unaffected by the volume fraction of drug in the walls. Copyright © 2017 Elsevier B.V. All rights reserved.

Photoactivated Composite Biomaterial for Soft Tissue Restoration in Rodents and in Humans

PubMed Central

Nahas, Zayna; Reid, Branden; Coburn, Jeannine M.; Axelman, Joyce; Chae, Jemin J.; Guo, Qiongyu; Trow, Robert; Thomas, Andrew; Hou, Zhipeng; Lichtsteiner, Serge; Sutton, Damon; Matheson, Christine; Walker, Patricia; David, Nathaniel; Mori, Susumu; Taube, Janis M.; Elisseeff, Jennifer H.

2015-01-01

Soft tissue reconstruction often requires multiple surgical procedures that can result in scars and disfiguration. Facial soft tissue reconstruction represents a clinical challenge because even subtle deformities can severely affect an individual’s social and psychological function. We therefore developed a biosynthetic soft tissue replacement composed of poly(ethylene glycol) (PEG) and hyaluronic acid (HA) that can be injected and photocrosslinked in situ with transdermal light exposure. Modulating the ratio of synthetic to biological polymer allowed us to tune implant elasticity and volume persistence. In a small-animal model, implanted photocrosslinked PEG-HA showed a dose-dependent relationship between increasing PEG concentration and enhanced implant volume persistence. In direct comparison with commercial HA injections, the PEG-HA implants maintained significantly greater average volumes and heights. Reversibility of the implant volume was achieved with hyaluronidase injection. Pilot clinical testing in human patients confirmed the feasibility of the transdermal photocrosslinking approach for implantation in abdomen soft tissue, although an inflammatory response was observed surrounding some of the materials. PMID:21795587

Tough stimuli-responsive supramolecular hydrogels with hydrogen-bonding network junctions.

PubMed

Guo, Mingyu; Pitet, Louis M; Wyss, Hans M; Vos, Matthijn; Dankers, Patricia Y W; Meijer, E W

2014-05-14

Hydrogels were prepared with physical cross-links comprising 2-ureido-4[1H]-pyrimidinone (UPy) hydrogen-bonding units within the backbone of segmented amphiphilic macromolecules having hydrophilic poly(ethylene glycol) (PEG). The bulk materials adopt nanoscopic physical cross-links composed of UPy-UPy dimers embedded in segregated hydrophobic domains dispersed within the PEG matrix as comfirmed by cryo-electron microscopy. The amphiphilic network was swollen with high weight fractions of water (w(H2O) ≈ 0.8) owing to the high PEG weight fraction within the pristine polymers (w(PEG) ≈ 0.9). Two different PEG chain lengths were investigated and illustrate the corresponding consequences of cross-link density on mechanical properties. The resulting hydrogels exhibited high strength and resilience upon deformation, consistent with a microphase separated network, in which the UPy-UPy interactions were adequately shielded within hydrophobic nanoscale pockets that maintain the network despite extensive water content. The cumulative result is a series of tough hydrogels with tunable mechanical properties and tractable synthetic preparation and processing. Furthermore, the melting transition of PEG in the dry polymer was shown to be an effective stimulus for shape memory behavior.

Molar mass fractionation in aqueous two-phase polymer solutions of dextran and poly(ethylene glycol).

PubMed

Zhao, Ziliang; Li, Qi; Ji, Xiangling; Dimova, Rumiana; Lipowsky, Reinhard; Liu, Yonggang

2016-06-24

Dextran and poly(ethylene glycol) (PEG) in phase separated aqueous two-phase systems (ATPSs) of these two polymers, with a broad molar mass distribution for dextran and a narrow molar mass distribution for PEG, were separated and quantified by gel permeation chromatography (GPC). Tie lines constructed by GPC method are in excellent agreement with those established by the previously reported approach based on density measurements of the phases. The fractionation of dextran during phase separation of ATPS leads to the redistribution of dextran of different chain lengths between the two phases. The degree of fractionation for dextran decays exponentially as a function of chain length. The average separation parameters, for both dextran and PEG, show a crossover from mean field behavior to Ising model behavior, as the critical point is approached. Copyright © 2016 Elsevier B.V. All rights reserved.

Combination could be another tool for bowel preparation?

PubMed Central

Soh, Jae Seung; Kim, Kyung-Jo

2016-01-01

Optimal bowel preparation increases the cecal intubation rate and detection of neoplastic lesions while decreasing the procedural time and procedural-related complications. Although high-volume polyethylene glycol (PEG) solution is the most frequently used preparation for bowel cleansing, patients are often unwilling to take PEG solution due to its large volume, poor palatability, and high incidence of adverse events, such as abdominal bloating and nausea. Other purgatives include osmotic agents (e.g., sodium phosphate, magnesium citrate, and sodium sulfate), stimulant agents (e.g., senna, bisacodyl, and sodium picosulfate), and prokinetic agents (e.g., cisapride, mosapride, and itopride). A combination of PEG with an osmotic, stimulant, or prokinetic agent could effectively reduce the PEG solution volume and increase patients’ adherence. Some such solutions have been found in several published studies to not be inferior to PEG alone in terms of bowel cleansing quality. Although combination methods showed similar efficacy and safety, the value of these studies is limited by shortcomings in study design. New effective and well-tolerated combination preparations are required, in addition to rigorous new validated studies. PMID:26973388

Clonazepam release from bioerodible hydrogels based on semi-interpenetrating polymer networks composed of poly(epsilon-caprolactone) and poly(ethylene glycol) macromer.

PubMed

Cho, C S; Han, S Y; Ha, J H; Kim, S H; Lim, D Y

1999-04-30

Poly(ethylene glycol)(PEG) macromers terminated with acrylate groups and semi-interpenetrating polymer networks (SIPNs) composed of poly(epsilon-caprolactone)(PCL) and PEG macromer were synthesized to obtain a bioerodible hydrogel. Polymerization of PEG macromer resulted in the formation of cross-linked gels due to the multifunctionality of macromer. Glass transition temperature (Tg) and melting temperature (Tm) of PEG networks and PCL in the SIPNs were inner-shifted, indicating an interpenetration of PCL and PEG chains. Water content in the SIPNs increased with increasing PEG weight fraction due to the hydrophilicity of PEG. The amount of clonazepam (CNZ) released from the SIPNs increased with higher content in the SIPNs, lower drug loading, lower concentration of PEG macromer during the SIPNs preparation, and higher molecular weight of PEG. In particular, a combination with low PEG content and low CNZ solubility in water led to long-term constant release from these matrices in vitro and in vivo. Copyright.

Asymmetrical flow field-flow fractionation for the analysis of PEG-asparaginase.

PubMed

John, C; Herz, T; Boos, J; Langer, K; Hempel, G

2016-01-01

Monomethoxypolyethylene glycol L-asparaginase (PEG-ASNASE) is the PEGylated version of the enzyme L-asparaginase (ASNASE). Both are used for remission induction in acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). The treatment control is generally carried out by performing activity assays, though methods to determine the actual enzyme rather than its activity are rare. Using asymmetrical flow field-flow fractionation (AF4) offered the chance to develop a method capable of simultaneously measuring PEG-ASNASE and PEG. A method validation was performed in accordance with FDA guidelines for PEG-ASNASE from non-biological solutions. The method unfolded a linearity of 15-750 U/mL with coefficients of correlation of r(2)>0.99. The coefficients of variation (CV) for within-run and between-run variability were 1.18-10.15% and 2.43-8.73%, respectively. Furthermore, the method was used to perform stability tests of the product Oncaspar® (PEG-ASNASE) and estimation of the molecular weight by multi-angle light scattering (MALS) of stressed samples to correlate them with the corresponding activity. The findings indicate that Oncaspar® stock solution should not be stored any longer than 24 h at room temperature and cannot be frozen in pure aqueous media. The validated method might be useful for the pharmaceutical industry and its quality control of PEG-ASNASE production. Copyright © 2015 Elsevier B.V. All rights reserved.

Bowel preparations for colonoscopy: an RCT.

PubMed

Di Nardo, Giovanni; Aloi, Marina; Cucchiara, Salvatore; Spada, Cristiano; Hassan, Cesare; Civitelli, Fortunata; Nuti, Federica; Ziparo, Chiara; Pession, Andrea; Lima, Mario; La Torre, Giuseppe; Oliva, Salvatore

2014-08-01

The ideal preparation regimen for pediatric colonoscopy remains elusive, and available preparations continue to represent a challenge for children. The aim of this study was to compare the efficacy, safety, tolerability, and acceptance of 4 methods of bowel cleansing before colonoscopy in children. This randomized, investigator-blinded, noninferiority trial enrolled all children aged 2 to 18 years undergoing elective colonoscopy in a referral center for pediatric gastroenterology. Patients were randomly assigned to receive polyethylene glycol (PEG) 4000 with simethicon (PEG-ELS group) or PEG-4000 with citrates and simethicone plus bisacodyl (PEG-CS+Bisacodyl group), or PEG 3350 with ascorbic acid (PEG-Asc group), or sodium picosulfate plus magnesium oxide and citric acid (NaPico+MgCit group). Bowel cleansing was evaluated according to the Boston Bowel Preparation Scale. The primary end point was overall colon cleansing. Tolerability, acceptability, and compliance were also evaluated. Two hundred ninety-nine patients were randomly allocated to the 4 groups. In the per-protocol analysis, PEG-CS+Bisacodyl, PEG-Asc, and NaPico+MgCit were noninferior to PEG-ELS in bowel-cleansing efficacy of both the whole colon (P = .910) and colonic segments. No serious adverse events occurred in any group. Rates of tolerability, acceptability, and compliance were significantly higher in the NaPico+MgCit group. Low-volume PEG preparations (PEG-CS+Bisacodyl, PEG-Asc) and NaPico+MgCit are noninferior to PEG-ELS in children, representing an attractive alternative to high-volume regimens in clinical practice. Because of the higher tolerability and acceptability profile, NaPico+MgCit would appear as the most suitable regimen for bowel preparation in children. Copyright © 2014 by the American Academy of Pediatrics.

Low-volume plus ascorbic acid vs high-volume plus simethicone bowel preparation before colonoscopy

PubMed Central

Pontone, Stefano; Angelini, Rita; Standoli, Monica; Patrizi, Gregorio; Culasso, Franco; Pontone, Paolo; Redler, Adriano

2011-01-01

AIM: To investigate the effectiveness of low-volume plus ascorbic acid [polyethylene glycol plus ascorbic acid (PEG + Asc)] and high-volume plus simethicone [polyethylene glycol plus simethicone (PEG + Sim)] bowel preparations. METHODS: A total of one hundred and forty-four outpatients (76 males), aged from 20 to 84 years (median age 59.5 years), who attended our Department, were divided into two groups, age and sex matched, and underwent colonoscopy. Two questionnaires, one for patients reporting acceptability and the other for endoscopists evaluating bowel cleansing effectiveness according to validated scales, were completed. Indications, timing of examination and endoscopical findings were recorded. Biopsy forceps were used as a measuring tool in order to determine polyp endoscopic size estimation. Difficulty in completing the preparation was rated in a 5-point Likert scale (1 = easy to 5 = unable). Adverse experiences (fullness, cramps, nausea, vomiting, abdominal pain, headache and insomnia), number of evacuations and types of activities performed during preparation (walking or resting in bed) were also investigated. RESULTS: Seventy-two patients were selected for each group. The two groups were age and sex matched as well as being comparable in terms of medical history and drug therapies taken. Fourteen patients dropped out from the trial because they did not complete the preparation procedure. Ratings of global bowel cleansing examinations were considered to be adequate in 91% of PEG + Asc and 88% of PEG + Sim patients. Residual Stool Score indicated similar levels of amount and consistency of residual stool; there was a significant difference in the percentage of bowel wall visualization in favour of PEG + Sim patients. In the PEG + Sim group, 12 adenomas ≤ 10 mm diameter (5/left colon + 7/right colon) vs 9 (8/left colon + 1/right colon) in the PEG + Asc group were diagnosed. Visualization of small lesions seems to be one of the primary advantages of the PEG + Sim preparation. CONCLUSION: PEG + Asc is a good alternative solution as a bowel preparation but more improvements are necessary in order to achieve the target of a perfect preparation. PMID:22180711

Low-volume plus ascorbic acid vs high-volume plus simethicone bowel preparation before colonoscopy.

PubMed

Pontone, Stefano; Angelini, Rita; Standoli, Monica; Patrizi, Gregorio; Culasso, Franco; Pontone, Paolo; Redler, Adriano

2011-11-14

To investigate the effectiveness of low-volume plus ascorbic acid [polyethylene glycol plus ascorbic acid (PEG + Asc)] and high-volume plus simethicone [polyethylene glycol plus simethicone (PEG + Sim)] bowel preparations. A total of one hundred and forty-four outpatients (76 males), aged from 20 to 84 years (median age 59.5 years), who attended our Department, were divided into two groups, age and sex matched, and underwent colonoscopy. Two questionnaires, one for patients reporting acceptability and the other for endoscopists evaluating bowel cleansing effectiveness according to validated scales, were completed. Indications, timing of examination and endoscopical findings were recorded. Biopsy forceps were used as a measuring tool in order to determine polyp endoscopic size estimation. Difficulty in completing the preparation was rated in a 5-point Likert scale (1 = easy to 5 = unable). Adverse experiences (fullness, cramps, nausea, vomiting, abdominal pain, headache and insomnia), number of evacuations and types of activities performed during preparation (walking or resting in bed) were also investigated. Seventy-two patients were selected for each group. The two groups were age and sex matched as well as being comparable in terms of medical history and drug therapies taken. Fourteen patients dropped out from the trial because they did not complete the preparation procedure. Ratings of global bowel cleansing examinations were considered to be adequate in 91% of PEG + Asc and 88% of PEG + Sim patients. Residual Stool Score indicated similar levels of amount and consistency of residual stool; there was a significant difference in the percentage of bowel wall visualization in favour of PEG + Sim patients. In the PEG + Sim group, 12 adenomas ≤ 10 mm diameter (5/left colon + 7/right colon) vs 9 (8/left colon + 1/right colon) in the PEG + Asc group were diagnosed. Visualization of small lesions seems to be one of the primary advantages of the PEG + Sim preparation. PEG + Asc is a good alternative solution as a bowel preparation but more improvements are necessary in order to achieve the target of a perfect preparation.

Chemical modification of protein A chromatography ligands with polyethylene glycol. I: Effects on IgG adsorption equilibrium, kinetics, and transport.

PubMed

Weinberg, Justin; Zhang, Shaojie; Crews, Gillian; Carta, Giorgio; Przybycien, Todd

2018-04-20

Chemical modification of Protein A (ProA) chromatography ligands with polyethylene glycol (PEGylation) has been proposed as a strategy to increase the process selectivity and resin robustness by providing the ligand with a steric repulsion barrier against non-specific binding. This article comprises a comprehensive study of IgG adsorption and transport in Repligen CaptivA PriMAB resin with PEGylated ProA ligands that are modified using 5.2 and 21.5 kDa PEG chains. We studied the impact of the molecular weight of the PEG as well as the extent of PEGylation for the 5.2 kDa PEG modification. In all cases, PEGylation of ProA ligands decreases the resin average pore size, particle porosity, and static binding capacity for IgG proportional to the volume of conjugated PEG in the resin. Resin batch uptake experiments conducted in bulk via a stirred-tank system and with individual resin particles under confocal laser scanning microscopy suggests that PEGylation introduces heterogeneity into IgG binding kinetics: a fraction of the IgG binding sites are transformed from typical fast association kinetic behavior to slow kinetic behavior. pH gradient elution experiments of an IgG molecule on the modified resins show an increase in IgG elution pH for all modified resins, implying a decrease in IgG-ProA binding affinity on modification. Despite losses in static binding capacity for all resins with PEGylated ligands, the loss of dynamic binding capacity at 10% breakthrough (DBC 10% ) ranged more broadly from almost 0-47% depending on the PEG molecular weight and the extent of PEGylation. Minimal losses in DBC 10% were observed with a low extent of PEGylation with a smaller molecular weight PEG, while higher losses were observed at higher extents of PEGylation and with higher molecular weight PEG due to decreased static binding capacity and increased mass transfer resistance. This work provides insight into the practical implications for resin performance if PEGylation is considered as a strategy for selectivity enhancement in affinity chromatography with macromolecular ligands. Copyright © 2018 Elsevier B.V. All rights reserved.

High- versus low-volume polyethylene glycol plus laxative versus sennosides for colonoscopy preparation in children.

PubMed

Kierkus, Jaroslaw; Horvath, Andrea; Szychta, Monika; Woynarowski, Marek; Wegner, Agnieszka; Wiernicka, Anna; Dadalski, Maciej; Teisseyre, Mikolaj; Dziechciarz, Piotr

2013-08-01

Many protocols of bowel preparation are available for use in children; however, none of them is commonly accepted. The aim of the study was to evaluate the efficacy and acceptability of high-volume polyethylene glycol (PEG) versus low-volume PEG combined with bisacodyl (BPEG) versus sennosides for colonoscopy preparation in children. Participants ages 10 to 18 years were randomly assigned to receive either PEG 60 or PEG 30 mL kg⁻¹ day⁻¹ plus oral bisacodyl 10 to 15 mg/day or sennosides 2 mg kg⁻¹ day⁻¹ for 2 days. A blinded assessment of bowel cleansing was made by the endoscopist according to the Aronchick and Ottawa scales. Patient acceptability was evaluated with the visual-analog scale. Analysis was done on an available case analysis basis. Of 240 patients enrolled in the study 234 patients were available for analysis of the efficacy of colon cleansing. There were no significant differences found among the 3 groups for the proportions of participants with excellent/good (PEG: 35/79, BPEG: 26/79, sennosides 25/76) and poor/inadequate (PEG: 20/79, BPEG: 28/79, sennosides 28/76) bowel preparation evaluated with the Aronchick scale and for the mean Ottawa total score (PEG: 5.47 ± 3.63, BPEG: 6.22 ± 3.3, sennosides: 6.18 ± 3.53). Acceptability of bowel cleansing protocol was similar in all of the groups (P = 0.8). All 3 cleansing methods showed similar efficacy and tolerability; however, none of them was satisfactory.

Bio-orthogonal coupling on PEG-modified quantum dots (Conference Presentation)

NASA Astrophysics Data System (ADS)

Zhan, Naiqian; Palui, Goutam; Mattoussi, Hedi

2017-02-01

We have designed two sets of aldehyde- and azide-modified ligands; these ligands also present lipoic acid anchors and PEG hydrophilic moieties (LA-PEG-CHO and LA-PEG-azide). We combined this design with a photoligation strategy to prepare QDs with good control over the fraction of intact reactive groups per nanocrystal. We first applied the extremely efficient hydrazone coupling ligation to react the QD with hydrozinopyridine, which produces a well-defined absorption feature at 354 nm ascribed to the hydrazone chromophore. We exploited this signature to measure the number of aldehyde groups per QD when the fraction of LA-PEG-CHO per nanocrystal was varied, by comparing the optical signature at 354 with the molar extinction coefficient of the chromophore. This allowed us to extract an estimate for the number of LA-PEG ligand per QDs for a few distinct size nanocrystals. We further complemented these findings with the use of NMR spectroscopy to estimate of the ligand density using well defined signatures of the terminal protons of the ligands, and found a good agreement between the two techniques. We then showed that bio-orthogonal reactions based on CLICK and hydrazone coupling can be achieved using QDs presenting a mixture of azide and CHO functions. We anticipate that this strategy could be applied other nanoparticles such as those of Au and metals and semiconductor nanocrystals.

Same-day 2-L PEG-citrate-simethicone plus bisacodyl vs split 4-L PEG: Bowel cleansing for late-morning colonoscopy

PubMed Central

de Leone, Annalisa; Tamayo, Darina; Fiori, Giancarla; Ravizza, Davide; Trovato, Cristina; De Roberto, Giuseppe; Fazzini, Linda; Dal Fante, Marco; Crosta, Cristiano

2013-01-01

AIM: To evaluate the efficacy, tolerability, acceptability and feasibility of bisacodyl plus low volume polyethyleneglycol-citrate-simeticone (2-L PEG-CS) taken the same day as compared with conventional split-dose 4-L PEG for late morning colonoscopy. METHODS: Randomised, observer-blind, parallel group, comparative trial carried out in 2 centres. Out patients of both sexes, aged between 18 and 85 years, undergoing colonoscopy for diagnostic investigation, colorectal cancer screening or follow-up were eligible. The PEG-CS group received 3 bisacodyl tablets (4 tablets for patients with constipation) at bedtime and 2-L PEG-CS in the morning starting 5 h before colonoscopy. The control group received a conventional 4-L PEG formulation given as split regimen; the morning dose was taken with the same schedule of the low volume preparation. The Ottawa Bowel Preparation Scale (OBPS) score was used as the main outcome measure. RESULTS: A total of 164 subjects were enrolled and 154 completed the study; 78 in the PEG-CS group and 76 in the split 4-L PEG group. The two groups were comparable at baseline. The OBPS score in the PEG-CS group (3.09 ± 2.40) and in the PEG group (2.39 ± 2.55) were equivalent (difference +0.70; 95%CI: -0.09-1.48). This was confirmed by the rate of successful bowel cleansing in the PEG-CS group (89.7%) and in the PEG group (92.1%) (difference -2.4%; 95%CI: -11.40- 6.70). PEG-CS was superior in terms of mucosa visibility compared to PEG (85.7% vs 72.4%, P = 0.042). There were no significant differences in caecum intubation rate, time to reach the caecum and withdrawal time between the two groups. The adenoma detection rate was similar (PEG-CS 43.6% vs PEG 44.7%). No serious adverse events occurred. No difference was found in tolerability of the bowel preparations. Compliance was equal in both groups: more than 90% of subjects drunk the whole solution. Willingness to repeat the same bowel preparations was about 90% for both regimes. CONCLUSION: Same-day PEG-CS is feasible, effective as split-dose 4-L PEG for late morning colonoscopy and does not interfere with work and daily activities the day before colonoscopy. PMID:24044042

Same-day 2-L PEG-citrate-simethicone plus bisacodyl vs split 4-L PEG: Bowel cleansing for late-morning colonoscopy.

PubMed

de Leone, Annalisa; Tamayo, Darina; Fiori, Giancarla; Ravizza, Davide; Trovato, Cristina; De Roberto, Giuseppe; Fazzini, Linda; Dal Fante, Marco; Crosta, Cristiano

2013-09-16

To evaluate the efficacy, tolerability, acceptability and feasibility of bisacodyl plus low volume polyethyleneglycol-citrate-simeticone (2-L PEG-CS) taken the same day as compared with conventional split-dose 4-L PEG for late morning colonoscopy. Randomised, observer-blind, parallel group, comparative trial carried out in 2 centres. Out patients of both sexes, aged between 18 and 85 years, undergoing colonoscopy for diagnostic investigation, colorectal cancer screening or follow-up were eligible. The PEG-CS group received 3 bisacodyl tablets (4 tablets for patients with constipation) at bedtime and 2-L PEG-CS in the morning starting 5 h before colonoscopy. The control group received a conventional 4-L PEG formulation given as split regimen; the morning dose was taken with the same schedule of the low volume preparation. The Ottawa Bowel Preparation Scale (OBPS) score was used as the main outcome measure. A total of 164 subjects were enrolled and 154 completed the study; 78 in the PEG-CS group and 76 in the split 4-L PEG group. The two groups were comparable at baseline. The OBPS score in the PEG-CS group (3.09 ± 2.40) and in the PEG group (2.39 ± 2.55) were equivalent (difference +0.70; 95%CI: -0.09-1.48). This was confirmed by the rate of successful bowel cleansing in the PEG-CS group (89.7%) and in the PEG group (92.1%) (difference -2.4%; 95%CI: -11.40- 6.70). PEG-CS was superior in terms of mucosa visibility compared to PEG (85.7% vs 72.4%, P = 0.042). There were no significant differences in caecum intubation rate, time to reach the caecum and withdrawal time between the two groups. The adenoma detection rate was similar (PEG-CS 43.6% vs PEG 44.7%). No serious adverse events occurred. No difference was found in tolerability of the bowel preparations. Compliance was equal in both groups: more than 90% of subjects drunk the whole solution. Willingness to repeat the same bowel preparations was about 90% for both regimes. Same-day PEG-CS is feasible, effective as split-dose 4-L PEG for late morning colonoscopy and does not interfere with work and daily activities the day before colonoscopy.

A mild transient decrease of peripheral red blood cell counts induced by a suprapharmacological dose of pegylated human megakaryocyte growth and development factor in rats.

PubMed

Harada, K; Ide, Y; Tazunoki, Y; Imai, A; Yanagida, M; Kikuchi, Y; Imai, A; Ishii, H; Kawahara, J; Izumi, H; Kusaka, M; Tokiwa, T

1999-07-01

Previous studies have shown that pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) at suprapharmacological dose induces a mild transient decrease of red blood cell counts according to thrombopoiesis in normal mice. To unravel the mechanism underlying this mild transient decrease of red blood cells, we have studied the effect of PEG-rHuMGDF on the circulating plasma and blood volume, and the serum biochemical parameters of anaemia and splenectomy. Also, we have performed histological studies of the bone marrow and the spleen of PEG-rHuMGDF-treated rats. PEG-rHuMGDF (300 microg kg(-1)]) or vehicle was subcutaneously administered to rats once a day for up to five days. From day 6 after the start of PEG-rHuMGDF administration, the platelet counts and plateletcrit levels were significantly increased, reaching peak values on day 10, and recovering to normal by day 20. The red blood cell counts and the haematocrit levels were significantly decreased on day 6 to 13. The decreases in red blood cell levels and haematocrit produced by PEG-rHuMGDF treatment were mild and had recovered by day 15. The plasma and blood volumes were significantly increased on day 10 in PEG-rHuMGDF-treated rats. No alteration of the serum biochemical parameters for anaemia, iron or total bilirubin, were observed on day 10. The histological examination on day 10 revealed a marked increase in megakaryocytes and a slight decrease in erythropoiesis in the bone marrow of rats that received PEG-rHuMGDF (300 microg kg(-1)). There was also a slight increase in splenic megakaryocytes and erythropoiesis. The decrease of red blood cells by PEG-rHuMGDF was not affected by splenectomy. These results suggest that the mild transient decrease of red blood cells induced by PEG-rHuMGDF treatment for up to five days is based mainly on the increases in the plasma and blood volume. These events are secondary changes due to the regulation of the excess production of megakaryocytes in the marrow and the peripheral platelets.

Determining equilibrium osmolarity in poly(ethylene glycol)/chondrotin sulfate gels mimicking articular cartilage.

PubMed

Sircar, S; Aisenbrey, E; Bryant, S J; Bortz, D M

2015-01-07

We present an experimentally guided, multi-phase, multi-species polyelectrolyte gel model to make qualitative predictions on the equilibrium electro-chemical properties of articular cartilage. The mixture theory consists of two different types of polymers: poly(ethylene gylcol) (PEG), chondrotin sulfate (ChS), water (acting as solvent) and several different ions: H(+), Na(+), Cl(-). The polymer chains have covalent cross-links whose effect on the swelling kinetics is modeled via Doi rubber elasticity theory. Numerical studies on equilibrium polymer volume fraction and net osmolarity (difference in the solute concentration across the gel) show a complex interplay between ionic bath concentrations, pH, cross-link fraction and the average charge per monomer. Generally speaking, swelling is aided due to a higher average charge per monomer (or a higher particle fraction of ChS, the charged component of the polymer), low solute concentration in the bath, a high pH or a low cross-link fraction. A peculiar case arises at higher values of cross-link fraction, where it is observed that increasing the average charge per monomer leads to gel deswelling. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dissipative particle dynamics parameterization and simulations to predict negative volume excess and structure of PEG and water mixtures

NASA Astrophysics Data System (ADS)

Kacar, Gokhan

2017-12-01

We report the results of dissipative particle dynamics (DPD) parameterization and simulations of a mixture of hydrophilic polymer, PEG 400, and water which are known to exhibit negative volume excess property upon mixing. The addition of a Morse potential to the conventional DPD potential mimics the hydrogen bond attraction, where the parameterization takes the internal chemistry of the beads into account. The results indicate that the mixing of PEG and water are maintained by the influence of hydrogen bonds, and the mesoscopic structure is characterized by the trade-off of enthalpic and entropic effects.

Colloidal Mechanisms of Gold Nanoparticle Loss in Asymmetric Flow Field-Flow Fractionation.

PubMed

Jochem, Aljosha-Rakim; Ankah, Genesis Ngwa; Meyer, Lars-Arne; Elsenberg, Stephan; Johann, Christoph; Kraus, Tobias

2016-10-07

Flow field-flow fractionation is a powerful method for the analysis of nanoparticle size distributions, but its widespread use has been hampered by large analyte losses, especially of metal nanoparticles. Here, we report on the colloidal mechanisms underlying the losses. We systematically studied gold nanoparticles (AuNPs) during asymmetrical flow field-flow fractionation (AF4) by systematic variation of the particle properties and the eluent composition. Recoveries of AuNPs (core diameter 12 nm) stabilized by citrate or polyethylene glycol (PEG) at different ionic strengths were determined. We used online UV-vis detection and off-line elementary analysis to follow particle losses during full analysis runs, runs without cross-flow, and runs with parts of the instrument bypassed. The combination allowed us to calculate relative and absolute analyte losses at different stages of the analytic protocol. We found different loss mechanisms depending on the ligand. Citrate-stabilized particles degraded during analysis and suffered large losses (up to 74%). PEG-stabilized particles had smaller relative losses at moderate ionic strengths (1-20%) that depended on PEG length. Long PEGs at higher ionic strengths (≥5 mM) caused particle loss due to bridging adsorption at the membrane. Bulk agglomeration was not a relevant loss mechanism at low ionic strengths ≤5 mM for any of the studied particles. An unexpectedly large fraction of particles was lost at tubing and other internal surfaces. We propose that the colloidal mechanisms observed here are relevant loss mechanisms in many particle analysis protocols and discuss strategies to avoid them.

Revealing thermal behavior of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) and its polyethylene glycol blends thin films: Effect of 3-Hydroxyhexanoate comonomer content

NASA Astrophysics Data System (ADS)

Chen, Yujing; Noda, Isao; Jung, Young Mee

2018-06-01

The 3-hydroxyhexanoate (HHx) molar fraction has a great effect on the property of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHx). In the present study, we investigated the influence of HHx comonomer molar fraction on the thermal property of PHBHx with 3.9 mol% (PHBHx3.9) and 13 mol% HHx (PHBHx13) comonomer content and their polyethylene glycol (PEG) blends in thin films by temperature-dependent infrared-reflection absorbance spectroscopy (IRRAS) and two-dimensional correlation (2D-COS) analysis. 2D-COS analysis demonstrated that there are two distinct amorphous bands of Cdbnd O stretching of PHBHx13 during the heating process, respectively at 1752 and 1760 cm-1, while PHBHx3.9 only shows one amorphous band at 1756 cm-1. This is due to the increase of HHx content from 3.9 mol % to 13 mol % increases the amorphous state of PHBHx. Furthermore, with incorporation of 30 wt% PEG, an additional amorphous band at 1746 cm-1 was observed in the case of 70/30 PHBHx3.9/PEG during the heating process, while this band was absent in the case of 70/30 PHBHx13/PEG, suggesting that the influence of PEG on PHBH3.9 is different from PHBHx13.

The effect of epsilon-caproyl/D,L-lactyl unit composition on the hydrolytic degradation of poly(D,L-lactide-ran-epsilon-caprolactone)-poly(ethylene glycol)-poly(D,L-lactide-ran-epsilon-caprolactone).

PubMed

Cho, Hanjin; An, Jeongho

2006-02-01

The degradation of P(DLAX-ran-CLY)-b-PEG-b-P(DLAX-ran-CLY)s ( P(DLAX-ran-CLY): Poly(D,L-lactide-ran-epsilon-caprolactone), PEG: Poly(ethylene glycol), X: D,L-lactyl unit fraction, Y: epsilon-caproyl unit fraction) is investigated. The fraction of DLA in the both end blocks is varied while the overall molecular weight and molecular weight of PEG are kept constant. DSC, XRD and GPC are employed to track the degradation process up to 200 days. Also the change in the surface and cross-sectional morphology is provided by SEM micro-photographs. The result of water absorption and weight loss characterization reveals that the incorporation of DLA in the polyester block could be an effective tool to facilitate degradation as well as water absorption. By tracking the change of molecular weight and polydispersity, chain scission and transport or removal of degraded product from the specimen were found to play a complex role in overall degradation.

Water structure in polyethylene glycols for preservation of wooden artefacts. A NIR-FT-Raman spectroscopic investigation

NASA Astrophysics Data System (ADS)

Christensen, M.; Nielsen, O. F.; Jensen, P.; Schnell, U.

2005-02-01

The interaction between polyethylene glycol (PEG) and water in mixtures has been investigated with a particular emphasis on the existence of 'free' water with a tetragonal bulk-like water structure. PEG is used in museum preservation of wooden objects, where free water must be avoided due to the danger of further microbial growth, contractile capillary forces and aqueous transport in wooden archaeological artefacts. A NIR-FT-Raman instrument with excitation at 1064 nm was used for this investigation. The OH stretch region around 3200 cm-1 shows changes in intensity with changing water content and the R(νbar)-function was applied in order to observe free water in the 100-300 cm-1 region. Mixtures of PEG and water were investigated with water contents ranging from 0 to 90% volume. It was found that free water appears around 28-32% volume in a PEG 600 mixture.

Nanoparticle Delivery Of RNAi Therapeutics For Ocular Vesicant Injury

DTIC Science & Technology

2014-12-01

micellar nanoparticles stabilized with disulfide crosslinking, hypothesizing that PEG corona on micellar nanoparticles could reduce toxicity while...micelles. This is analogous to micelle assembly, where the shape control is governed by the volume ratio of the hydrophilic ( corona ) to...self-assembly of the complexes between siRNA and LPEI-g-PEG copolymer carriers. The PEG corona and reversibly crosslinked core of the micelles enable

Bioprinting 3D cell-laden hydrogel microarray for screening human periodontal ligament stem cell response to extracellular matrix.

PubMed

Ma, Yufei; Ji, Yuan; Huang, Guoyou; Ling, Kai; Zhang, Xiaohui; Xu, Feng

2015-12-22

Periodontitis is an inflammatory disease negatively affecting up to 15% of adults worldwide. Periodontal ligament stem cells (PDLSCs) hold great promises for periodontal tissue regeneration, where it is necessary to find proper extracellular matrix (ECM) materials (e.g., composition, concentration). In this study, we proposed a bioprinting-based approach to generate nano-liter sized three-dimensional (3D) cell-laden hydrogel array with gradient of ECM components, through controlling the volume ratio of two hydrogels, such as gelatin methacrylate (GelMA) and poly(ethylene glycol) (PEG) dimethacrylate. The resulting cell-laden array with a gradient of GelMA/PEG composition was used to screen human PDLSC response to ECM. The behavior (e.g., cell viability, spreading) of human PDLSCs in GelMA/PEG array were found to be depended on the volume ratios of GelMA/PEG, with cell viability and spreading area decreased along with increasing the ratio of PEG. The developed approach would be useful for screening cell-biomaterial interaction in 3D and promoting regeneration of functional tissue.

Dynamics of gold nanoparticles in synthetic and biopolymer solutions

NASA Astrophysics Data System (ADS)

Kohli, Indermeet

Soft matter systems of colloidal particles, polymers, amphiphiles and liquid crystals are ubiquitous in our everyday life. Food, plastics, soap and even human body is comprised of soft materials. Research conducted to understand the behavior of these soft matter systems at molecular level is essential for many interdisciplinary fields of study as well as important for many technological applications. We used gold nanoparticles (Au NPs) to investigate the length-scale dependent dynamics in semidilute poly(ethylene glycol) (PEG)-water, bovine serum albumin (BSA)-phosphate buffer, dextran and particulate solutions. In case of PEG-water solutions, fluctuation correlation spectroscopy was used to measure the diffusion coefficients (D) of the NPs as a function of their radius, Ro (2.5-10 nm), PEG volume fraction, φ (0-0.37) and molecular weight, Mw (5 kg/mol and 35 kg/mol). Our results indicate that the radius of gyration, Rg of the polymer chain is the crossover length scale for the NPs experiencing nanoviscosity or macroviscosity. In BSA-phosphate buffer solutions, we observed a monolayer formation at the NP surface with a thickness of 3.8 nm. The thickness of the adsorbed layer was independent of NP size. Best fit was obtained by the anticooperative binding model with the Hill coefficient of n = 0.63. Dissociation constant (KD) increased with particle size indicating stronger interaction of BSA with smaller sized NPs. We also contrasted the diffusion of gold nanoparticles (AuNPs) in crowded solutions of randomly branched polymer (dextran) and rigid, spherical particles (silica) to understand the roles played by the probe size and structure of the crowding agent in determining the probe diffusion. AuNPs of two different sizes (2.5 nm & 10 nm), dextran of molecular weight 70 kDa and silica particles of radius 10 nm were used. Our results indicated that the AuNP diffusion can be described using the bulk viscosity of the matrix and hydrodynamically dextran behaved similar to soft colloid. In all situations, we observed normal diffusion except for 2.5 nm sized AuNP particles in dextran solution at higher volume fraction. This was caused by transient trapping of particles within the random branches. The results showed the importance of macromolecular architecture in determining the transport properties in intracellular matrix and in cells with spiny dendrites.

Online open-tubular fractionation scheme coupled with push-pull perfusion sampling for profiling extravasation of gold nanoparticles in a mouse tumor model.

PubMed

Su, Cheng-Kuan; Tseng, Po-Jen; Lin, Meng-Han; Chiu, Hsien-Ting; del Vall, Andrea; Huang, Yu-Fen; Sun, Yuh-Chang

2015-07-10

The extravasation of administered nano-drug carriers is a critical process for determining their distributions in target and non-target organs, as well as their pharmaceutical efficacies and side effects. To evaluate the extravasation behavior of gold nanoparticles (AuNPs), currently the most popular drug delivery system, in a mouse tumor model, in this study we employed push-pull perfusion (PPP) as a means of continuously sampling tumor extracellular AuNPs. To facilitate quantification of the extravasated AuNPs through inductively coupled plasma mass spectrometry, we also developed a novel online open-tubular fractionation scheme to allow interference-free determination of the sampled extracellular AuNPs from the coexisting biological matrix. After optimizing the flow-through volume and flow rate of this proposed fractionation scheme, we found that (i) the system's temporal resolution was 7.5h(-1), (ii) the stability presented by the coefficient of variation was less than 10% (6-h continuous measurement), and (iii) the detection limits for the administered AuNPs were in the range 0.057-0.068μgL(-1). Following an intravenous dosage of AuNPs (0.3mgkg(-1) body weight), in vivo acquired profiles indicated that the pegylated AuNPs (PEG-AuNPs) had greater tendency toward extravasating into the tumor extracellular space. We also observed that the accumulation of nanoparticles in the whole tumor tissues was higher for PEG-AuNPs than for non-pegylated ones. Overall, pegylation appears to promote the extravasation and accumulation of AuNPs for nano-drug delivery applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Simethicone improves bowel cleansing with low-volume polyethylene glycol: a multicenter randomized trial.

PubMed

Zhang, Shenghong; Zheng, Danping; Wang, Jinping; Wu, Jianwei; Lei, Pingguang; Luo, Qi; Wang, Liping; Zhang, Beiping; Wang, Hong; Cui, Yi; Chen, Minhu

2018-04-01

 For bowel preparation, using a reduced volume of polyethylene glycol (PEG) solution without influencing its effectiveness would be preferable. While simethicone shows great potential as an adjunctive agent, data on its use are limited. We aimed to clarify whether simethicone added to low-volume PEG solution improved bowel cleansing. PATIENTS AND METHODS : Consecutive adult patients registered for colonoscopy were recruited from seven medical centers in South China between 15 April and 15 July 2015 and prospectively randomized into two groups: 2 L PEG (conventional group) and 2 L PEG plus simethicone (simethicone group). The primary endpoint was the effectiveness of bowel cleansing according to the Boston Bowel Preparation Scale (BBPS). Secondary endpoints included cecal intubation time, adenoma detection rate (ADR), patient safety and compliance, and adverse events. RESULTS : We included 290 and 289 patients in the conventional and simethicone groups, respectively, for analysis. The proportion with acceptable bowel cleansing (BBPS ≥ 6) was significantly higher in the simethicone group than in the conventional group (88.2 % vs. 76.6 %; P  < 0.001). The mean (SD) BBPS score was significantly lower in the conventional group (6.5 [1.8] vs. 7.3 [1.7]; P  < 0.001), as was the bubble score (2.5 [0.7] vs. 2.8 [0.5]; P  < 0.001). The average cecal intubation time was significantly shorter in the simethicone group (6.3 [3.1] vs. 7.5 [5.1] minutes; P  < 0.001). The ADR in the right colon was higher in the simethicone group than in the conventional group (16.6 % vs. 10.3 %; P  = 0.03). Safety and compliance, including the taste, smell, and dosage of PEG, were similar for both groups.  Simethicone added to low-volume PEG solution improves bowel-cleansing efficacy, with similar safety and compliance, shorter cecal intubation time, and higher ADR. © Georg Thieme Verlag KG Stuttgart · New York.

Development of an alternative low salt bovine hide preservation using PEG and crude glycerol, part 1: evaluation of PEG molecular weight fractions

USDA-ARS?s Scientific Manuscript database

Brine curing using sodium chloride is widely used for the short-term preservation of cattle hides. Due to economics and efficiency, it has become the traditional method of hide preservation used by meat packers, hide processors, and tanners worldwide. But brine curing is known to cause serious efflu...

Stimulation of colonic motility by oral PEG electrolyte bowel preparation assessed by MRI: comparison of split vs single dose

PubMed Central

Marciani, L; Garsed, K C; Hoad, C L; Fields, A; Fordham, I; Pritchard, S E; Placidi, E; Murray, K; Chaddock, G; Costigan, C; Lam, C; Jalanka-Tuovinen, J; De Vos, W M; Gowland, P A; Spiller, R C

2014-01-01

Background Most methods of assessing colonic motility are poorly acceptable to patients. Magnetic resonance imaging (MRI) can monitor gastrointestinal motility and fluid distributions. We predicted that a dose of oral polyethylene glycol (PEG) and electrolyte solution would increase ileo-colonic inflow and stimulate colonic motility. We aimed to investigate the colonic response to distension by oral PEG electrolyte in healthy volunteers (HVs) and to evaluate the effect of single 2 L vs split (2 × 1 L) dosing. Methods Twelve HVs received a split dose (1 L the evening before and 1 L on the study day) and another 12 HVs a single dose (2 L on the main study day) of PEG electrolyte. They underwent MRI scans, completed symptom questionnaires, and provided stool samples. Outcomes included small bowel water content, ascending colon motility index, and regional colonic volumes. Key Results Small bowel water content increased fourfold from baseline after ingesting both split (p = 0.0010) and single dose (p = 0.0005). The total colonic volume increase from baseline was smaller for the split dose at 35 ± 8% than for the single dose at 102 ± 27%, p = 0.0332. The ascending colon motility index after treatment was twofold higher for the single dose group (p = 0.0103). Conclusions & Inferences Ingestion of 1 and 2 L PEG electrolyte solution caused a rapid increase in the small bowel and colonic volumes and a robust rise in colonic motility. The increase in both volumes and motility was dose dependent. Such a challenge, being well-tolerated, could be a useful way of assessing colonic motility in future studies. PMID:25060551

Polyethylene glycol powder solution versus senna for bowel preparation for colonoscopy in children.

PubMed

Terry, Natalie A; Chen-Lim, Mei Lin; Ely, Elizabeth; Jatla, Muralidhar; Ciavardone, Denise; Esch, Salina; Farace, Lisa; Jannelli, Frances; Puma, Anita; Carlow, Dean; Mamula, Petar

2013-02-01

Safety and effectiveness of large-volume polyethylene glycol-based solution (PEG-ES) have been documented, but the taste and volume can be barriers to successful colonoscopy preparation. Efficacy and safety of small-volume electrolyte-free (PEG-P) preparation (Miralax) for colonoscopy preparation have been rarely studied, although presently used at many pediatric centers. The primary objective of the present study was to determine whether PEG-P results in a more efficacious and safe colonoscopy preparation as compared with senna. The study design was prospective, randomized, and single-blinded. Patients ages 6 to 21 years were randomized to a 2-day clean-out regimen of PEG-P at a dose of 1.5 g/kg divided twice per day for 2 days versus senna 15 mL daily (ages 6-12) or 30 mL daily (ages 12-21) for 2 days. Both preparations required 1 day of clear liquids whereas senna preparation required an additional day of full liquid diet. A blinded endoscopist graded the quality of preparation with a standardized cleanliness tool (Aronchick scale). Serum chemistry panels were obtained. Patients or parents rated symptoms and ease of preparation. The anticipated number of subjects was 166; however, the interim analysis demonstrated inferiority of senna preparation. Thirty patients were evaluated in the present study. Of the patients in the PEG-P arm, 88% (14/16) received an excellent/good score compared with 29% (4/14), with the senna preparation (P = 0.0022). Both preparations were well-tolerated by patient-graded ease of preparation. Demographics and laboratory values did not differ significantly across the 2 groups. No serious adverse events were noted. PEG-P is an effective colonoscopy preparation whereas senna preparation was insufficient. Both were well-tolerated and appear safe in a pediatric population.

Delivery of kinesin spindle protein targeting siRNA in solid lipid nanoparticles to cellular models of tumor vasculature

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ying, Bo; Campbell, Robert B., E-mail: robert.campbell@mcphs.edu

2014-04-04

Highlights: • siRNA-lipid nanoparticles are solid particles not lipid bilayers with aqueous core. • High, but not low, PEG content can prevent nanoparticle encapsulation of siRNA. • PEG reduces cellular toxicity of cationic nanoparticles in vitro. • PEG reduces zeta potential while improving gene silencing of siRNA nanoparticles. • Kinesin spindle protein can be an effective target for tumor vascular targeting. - Abstract: The ideal siRNA delivery system should selectively deliver the construct to the target cell, avoid enzymatic degradation, and evade uptake by phagocytes. In the present study, we evaluated the importance of polyethylene glycol (PEG) on lipid-based carriermore » systems for encapsulating, and delivering, siRNA to tumor vessels using cellular models. Lipid nanoparticles containing different percentage of PEG were evaluated based on their physical chemical properties, density compared to water, siRNA encapsulation, toxicity, targeting efficiency and gene silencing in vitro. siRNA can be efficiently loaded into lipid nanoparticles (LNPs) when DOTAP is included in the formulation mixture. However, the total amount encapsulated decreased with increase in PEG content. In the presence of siRNA, the final formulations contained a mixed population of particles based on density. The major population which contains the majority of siRNA exhibited a density of 4% glucose, and the minor fraction associated with a decreased amount of siRNA had a density less than PBS. The inclusion of 10 mol% PEG resulted in a greater amount of siRNA associated with the minor fraction. Finally, when kinesin spindle protein (KSP) siRNA was encapsulated in lipid nanoparticles containing a modest amount of PEG, the proliferation of endothelial cells was inhibited due to the efficient knock down of KSP mRNA. The presence of siRNA resulted in the formation of solid lipid nanoparticles when prepared using the thin film and hydration method. LNPs with a relatively modest amount of PEG can sufficiently encapsulate siRNA, improve cellular uptake and the efficiency of gene silencing.« less

Polyethylene Glycol Based Graphene Aerogel Confined Phase Change Materials with High Thermal Stability.

PubMed

Fu, Yang; Xiong, Weilai; Wang, Jianying; Li, Jinghua; Mei, Tao; Wang, Xianbao

2018-05-01

Polyethylene glycol (PEG) based graphene aerogel (GA) confined shaped-stabilized phase change materials (PCMs) are simply prepared by a one-step hydrothermal method. Three-dimensional GA inserted by PEG molecule chains, as a supporting material, obtained by reducing graphene oxide sheets, is used to keep their stabilized shape during a phase change process. The volume of GA is obviously expended after adding PEG, and only 9.8 wt% of GA make the composite achieve high energy efficiency without leakage during their phase change because of hydrogen bonding widely existing in the GA/PEG composites (GA-PCMs). The heat storage energy of GA-PCMs is 164.9 J/g, which is 90.2% of the phase change enthalpy of pure PEG. In addition, this composite inherits the natural thermal properties of graphene and thus shows enhanced thermal conductivity compared with pure PEG. This novel study provides an efficient way to fabricate shape-stabilized PCMs with a high content of PEG for thermal energy storage.

Elucidation of the Structure Formation of Polymer-Conjugated Proteins in Solution and Block Copolymer Templates

NASA Astrophysics Data System (ADS)

Ferebee, Rachel L.

The broader technical objective of this work is to contribute to the development of enzyme-functionalized nanoporous membranes that can function as autonomous and target selective dynamic separators. The scientific objective of the research performed within this thesis is to elucidate the parameters that control the mixing of proteins in organic host materials and in block copolymers templates in particular. A "biomimetic" membrane system that uses enzymes to selectively neutralize targets and trigger a change in permeability of nanopores lined with a pH-responsive polymer has been fabricated and characterized. Mechanical and functional stability, as well as scalability, have been demonstrated for this system. Additional research has focused on the role of polymeric ligands on the solubility characteristics of the model protein, Bovine Serum Albumin (BSA). For this purpose BSA was conjugated with poly(ethylene glycol) (PEG) ligands of varied degree of polymerization and grafting density. Combined static and dynamic light scattering was used (in conjunction with MALDI-TOF) to determine the second virial coefficient in PBS solutions. At a given mass fraction PEG or average number of grafts, the solubility of BSA-PEG conjugates is found to increase with the degree of polymerization of conjugated PEG. This result informs the synthesis of protein-conjugate systems that are optimized for the fabrication of block copolymer blend materials with maximum protein loading. Blends of BSA-PEG conjugates and block copolymer (BCP) matrices were fabricated to evaluate the dispersion morphology and solubility limits in a model system. Electron microscopy was used to evaluate the changes in lamellar spacing with increased filling fraction of BSA-PEG conjugates.

Miscibility and crystallization behavior of poly (3-hydroxybutyrate) and poly (ethylene glycol) blends studied by positron annihilation spectroscopy

NASA Astrophysics Data System (ADS)

Abdel-Hady, E. E.; Abdel-Hamed, M. O.; Hammam, A. M.

2011-01-01

Positron annihilation Lifetime (PAL) spectroscopy has been used to study the effect of PEG concentrations on the free volume properties of PHB. The data revealed that the ortho-positronium (o-Ps) lifetime τPs increases with 20% increase in concentration, decrease as the concentration increases to 40%, then rapid increase at 50% concentration of PEG. The o-Ps intensity, I3, shows a linear dependence as the concentration increases with a discontinuity at 20% concentration of PEG. Furthermore, the results presented and discussed in this work show that the PHB and PEG are miscible up to 40% of PEG but greater than 40%, the blend is immiscible. In addition, the mechanical properties of PHB are well improved by the addition of PEG with a low concentration up to 20%, while at higher concentration the blend becomes waxy.

Randomised clinical trial: Polyethylene glycol 3350 with sports drink vs. polyethylene glycol with electrolyte solution as purgatives for colonoscopy--the incidence of hyponatraemia.

PubMed

Matro, R; Daskalakis, C; Negoianu, D; Katz, L; Henry, C; Share, M; Kastenberg, D

2014-09-01

Polyethylene glycol 3350 plus sports drink (PEG-SD) is a hypo-osmotic purgative commonly used for colonoscopy, though little safety data are available. To evaluate the effect of PEG-SD on serum sodium (Na) and other electrolytes compared with PEG-electrolyte solution (PEG-ELS). We performed a single center, prospective, randomised, investigator-blind comparison of PEG-ELS to PEG-SD in out-patients undergoing colonoscopy. Laboratories were obtained at baseline and immediately before and after colonoscopy. The primary endpoint was development of hyponatraemia (Na <135 mmol/L) the day of colonoscopy. Changes in electrolyte levels were computed as the difference between the lowest value on the day of colonoscopy and baseline. Purgative tolerance and efficacy were assessed. A total of 389 patients were randomised; 364 took purgative and had baseline and day of colonoscopy labs (180 PEG-SD, 184 PEG-ELS). The groups were well matched except for a higher fraction of women and Blacks in PEG-ELS. Seven patients (3.9%) in PEG-SD and four patients (2.2%) in PEG-ELS developed hyponatraemia (OR = 1.82, 95% CI: 0.45-8.62, P = 0.376). Changes in electrolytes from baseline were small but significantly worse with PEG-SD for sodium, potassium and chloride (P = 0.001, 0.012, 0.001, respectively). Preparation completion, adverse events, and overall colon cleansing were similar between the groups, but PEG-ELS had more excellent preparations (52% vs. 30%; P = 0.001). Greater, but very modest, electrolyte changes occur with PEG-SD. Hyponatraemia is infrequent with both purgatives. A significant increase in hyponatraemia was not identified for PEG-SD vs. PEG-ELS, but the sample size may have been inadequate to identify a small, but clinically important difference. ClinicalTrials.gov identifier NCT01299779. © 2014 John Wiley & Sons Ltd.

Validation of polyethylene glycol 3350 as a poorly absorbable marker for intestinal perfusion studies.

PubMed

Schiller, L R; Santa Ana, C A; Porter, J; Fordtran, J S

1997-01-01

Polyethylene glycol (PEG) has been used as a poorly absorbable marker in intestinal perfusion studies, but there is controversy about the absorbability of PEG, particularly when glucose-sodium cotransport is occurring. Total intestinal perfusion studies were done in five normal humans using three solutions containing 1 g/liter PEG 3350 and designed to produce low rates of water absorption, high rates of water absorption, or high rates of glucose-sodium cotransport. Water absorption rates were calculated by traditional nonabsorbable marker equations and by a novel balance technique in which absorption was taken as the difference between the volumes of solution infused and recovered during steady-state conditions. Effluent PEG recovery was 99 +/- 4%, 109 +/- 2%, and 104 +/- 6% of the amount infused with each solution. Water absorption rates measured by use of PEG concentrations were similar to those calculated by the balance technique (r = 0.99). The complete recovery of PEG confirms the poor absorbability of PEG 3350, and the excellent agreement between techniques validates PEG as a poorly absorbed marker, even when glucose-sodium cotransport is occurring.

Effect of polyethylene glycol on the liquid–liquid phase transition in aqueous protein solutions

PubMed Central

Annunziata, Onofrio; Asherie, Neer; Lomakin, Aleksey; Pande, Jayanti; Ogun, Olutayo; Benedek, George B.

2002-01-01

We have studied the effect of polyethylene glycol (PEG) on the liquid–liquid phase separation (LLPS) of aqueous solutions of bovine γD-crystallin (γD), a protein in the eye lens. We observe that the phase separation temperature increases with both PEG concentration and PEG molecular weight. PEG partitioning, which is the difference between the PEG concentration in the two coexisting phases, has been measured experimentally and observed to increase with PEG molecular weight. The measurements of both LLPS temperature and PEG partitioning in the ternary γD-PEG-water systems are used to successfully predict the location of the liquid–liquid phase boundary of the binary γD-water system. We show that our LLPS measurements can be also used to estimate the protein solubility as a function of the concentration of crystallizing agents. Moreover, the slope of the tie-lines and the dependence of LLPS temperature on polymer concentration provide a powerful and sensitive check of the validity of excluded volume models. Finally, we show that the increase of the LLPS temperature with PEG concentration is due to attractive protein–protein interactions. PMID:12391331

Mean platelet volume in pseudoexfoliation syndrome and glaucoma.

PubMed

Türkcü, Fatih Mehmet; Yüksel, Harun; Sahin, Alparslan; Cinar, Yasin; Yüksel, Hatice; Cingü, Kürşat; Sahin, Muhammed; Yildirim, Adnan; Çaça, Ihsan

2014-01-01

Pseudoexfoliation (PEX) syndrome (PES) is characterized by the widespread deposition of abnormal extracellular fibrillary material on many ocular and extraocular tissues. The objective of this study was to evaluate the association among PES, PEX glaucoma (PEG), and mean platelet volume (MPV). Forty patients with PES (mean age 62.6 ± 7.8 years), 31 with PEG (mean age 65.9 ± 6.6 years), and 37 healthy individuals (control group) (mean age 64.0 ± 7.1 years) were included in the study. The MPV of the 3 groups were compared. Age and sex distribution were similar among groups (p>0.05). Mean MPV in PES, PEG, and control groups were 9.59 ± 0.94 fl, 9.53 ± 0.80 fl, and 7.7 ± 0.67 fl, respectively. In the PEX group, MPV values were significantly higher than in the control group (p<0.05). However, there was no difference between the PES and PEG groups (p>0.05). The MPV values in both groups with PEX were higher than those in the healthy group.

Antitumoral activity and toxicity of PEG-coated and PEG-folate-coated pH-sensitive liposomes containing ¹⁵⁹Gd-DTPA-BMA in Ehrlich tumor bearing mice.

PubMed

Soares, Daniel Crístian Ferreira; Cardoso, Valbert Nascimento; de Barros, André Luís Branco; de Souza, Cristina Maria; Cassali, Geovanni Dantas; de Oliveira, Mônica Cristina; Ramaldes, Gilson Andrade

2012-01-23

In the present study, PEG-coated pH-sensitive and PEG-folate-coated pH-sensitive liposomes containing the ¹⁵⁹Gd-DTPA-BMA were prepared and radiolabeled through neutron activation technique, aiming to study the in vivo antitumoral activity and toxicity on mice bearing a previously-developed solid Ehrlich tumor. The treatment efficacy was verified through tumoral volume increase and histomorphometry studies. The toxicity of formulations was investigated through animal weight variations, as well as hematological and biochemical tests. The results showed that after 31 days of treatment, animals treated with radioactive formulations had a lower increase in tumor volume and a significantly higher percentage of necrosis compared with controls revealed by histomorphometry studies. Furthermore, mice treated with radioactive formulations exhibited lower weight gain without significant hematological or biochemical changes, except for toxicity to hepatocytes which requires more detailed studies. From the results obtained to date, we believe that the radioactive formulations can be considered potential therapeutic agents for cancer. Copyright © 2011 Elsevier B.V. All rights reserved.

Preparation before colonoscopy: a randomized controlled trial comparing different regimes.

PubMed

Jansen, Sita V; Goedhard, Jelle G; Winkens, Bjorn; van Deursen, Cees Th B M

2011-10-01

A good bowel preparation is essential for optimal visualization of the large intestine. Several preparations with a difference in composition and volume are available. We compared five methods for bowel cleansing quality and patients' acceptability. Adult ambulatory outpatients scheduled for elective colonoscopy were randomized to receive 4-l polyethylene glycol (PEG) solution (Klean-prep), 2-l PEG solution+ascorbic acid (Moviprep), or a sodium phosphate (NaP) solution, Phosphoral. Patients with the PEG solutions were also randomized to receive simethicone (Aeropax), to investigate whether this improves the bowel cleansing efficacy. Before colonoscopy patients completed a questionnaire about the acceptability and tolerability of the preparation. Endoscopists blinded to the type of preparation gave a bowel cleansing score. Data were available for 461 patients. 2-l PEG+ascorbic acid was noninferior to 4-l PEG in bowel cleansing quality of rectosigmoid and colon. NaP was noninferior to 4-l PEG in bowel cleansing quality of rectosigmoid but inferior for the whole colon. Compliance was significantly less in the group with 4-l PEG compared with the 2-l PEG and NaP group. No difference was found for abdominal cramps. Taste was significantly better in the 2-l PEG group. Simethicone did not improve the bowel cleansing quality. 2-l PEG+ascorbic acid was noninferior to the 4-l PEG solution in bowel cleansing quality and was better in taste and compliance. NaP was inferior to 4-l PEG in bowel cleansing quality. Addition of simethicone gave no improvement.

The "New Polyethylene Glycol Dilemma": Polyethylene Glycol Impurities and Their Paradox Role in mAb Crystallization.

PubMed

Hildebrandt, Christian; Joos, Lea; Saedler, Rainer; Winter, Gerhard

2015-06-01

Polyethylene glycols (PEG) represent the most successful and frequently applied class of excipients used for protein crystallization. PEG auto-oxidation and formation of impurities such as peroxides and formaldehydes that foster protein drug degradation is known. However, their effect on mAb crystallization has not been studied in detail before. During the present study, a model IgG1 antibody (mAb1) was crystallized in PEG solutions. Aggregate formation was observed during crystallization and storage that was ascribed to PEG degradation products. Reduction of peroxide and formaldehyde levels prior to crystallization by vacuum and freeze-drying was investigated for its effect on protein degradation. Vacuum drying was superior in removal of peroxides but inferior in reducing formaldehyde residues. Consequently, double purification allowed extensive removal of both impurities. Applying of purified PEG led to 50% lower aggregate fractions. Surprisingly, PEG double purification or addition of methionine prior to crystallization prevented crystal formation. With increased PEG concentration or spiking with peroxides and formaldehydes, crystal formation could be recovered again. With these results, we demonstrate that minimum amounts of oxidizing impurities and thus in consequence chemically altered proteins are vital to initiate mAb1 crystallization. The present study calls PEG as good precipitant for therapeutic biopharmaceuticals into question. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Radioprotective effect of polyethylene glycol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shaeffer, J.; Schellenberg, K.A.; Seymore, C.H.

1986-07-01

Polyethylene glycol of molecular weight 400 (PEG-400) had a radioprotective effect of about 20% against lethality when given ip 20 min prior to single or fractionated X-ray doses to the head and neck. Dose modification factors (DMF) based on LD50/15 values ranged from 1.14 to 1.24. A similar DMF of 1.12 based on LD50/30 values was obtained using single doses of whole-body X irradiation. Mice given head and neck irradiation had significantly reduced rectal temperatures (31.3 +/- 3.0/sup 0/C) 9 days post irradiation compared with unirradiated controls (35.4 +/- 0.6/sup 0/C). No such reduction was observed when PEG-400 was givenmore » with radiation (36.3 +/- 0.9/sup 0/C). PEG-400 also lessened, but not significantly, the frequency of shivering in irradiated animals. Histopathologic examination of the oral structures demonstrated only marginal protection by PEG-400. Estimation of the alpha/beta ratio from LD50 data on head and neck-irradiated mice yielded values of 4.4 +/- 1.9 (95% confidence limits) Gy without PEG-400 and 7.9 +/- 1.4 Gy with PEG-400. Since it is a non-thiol radioprotector, PEG-400 may be more useful when combined with more conventional thiol-containing radioprotectors.« less

A Study on the Impact of Poly(3-hexylthiophene) Chain Length and Other Applied Side-Chains on the NO2 Sensing Properties of Conducting Graft Copolymers

PubMed Central

Kepska, Kinga

2018-01-01

The detection and concentration measurements of low concentrations of nitrogen dioxide (NO2) are important because of its negative effects on human health and its application in many fields of industry and safety systems. In our approach, conducting graft copolymers based on the poly(3-hexylthiophene) (P3HT) conducting polymer and other side-chains, polyethylene glycol (PEG) and dodec-1-en, grafted on a poly(methylhydrosiloxane) backbone, were investigated. The grafts containing PEG (PEGSil) and dodec-1-en (DodecSil) in two variants, namely, fractions with shorter (hexane fraction -H) and longer (chloroform fraction -CH) side-chains of P3HT, were tested as receptor structures in NO2 gas sensors. Their responses to NO2, within the concentration range of 1–20 ppm, were investigated in an nitrogen atmosphere at different operating temperatures—room temperature (RT) = 25 °C, 50 °C, and 100 °C. The results indicated that both of the copolymers with PEG side-chains had higher responses to NO2 than the materials with dodec-1-en side-chains. Furthermore, the results indicated that, in both cases, H fractions were more sensitive than CH fractions. The highest response to 1 ppm of NO2, from the investigated graft copolymers, had PEGSil H, which indicated a response of 1330% at RT and 1980% at 100 °C. The calculated lower-limit of the detection of this material is lower than 300 ppb of NO2 at 100 °C. This research indicated that graft copolymers of P3HT had great potential for low temperature NO2 sensing, and that the proper choice of other side-chains in graft copolymers can improve their gas sensing properties. PMID:29558448

Quantifying the density of surface capping ligands on semiconductor quantum dots

NASA Astrophysics Data System (ADS)

Zhan, Naiqian; Palui, Goutam; Merkl, Jan-Philip; Mattoussi, Hedi

2015-03-01

We have designed a new set of coordinating ligands made of a lipoic acid (LA) anchor and poly(ethylene glycol) (PEG) hydrophilic moiety appended with a terminal aldehyde for the surface functionalization of QDs. This ligand design was combined with a recently developed photoligation strategy to prepare hydrophilic CdSe-ZnS QDs with good control over the fraction of intact aldehyde (-CHO) groups per nanocrystal. We further applied the efficient hydrazone ligation to react aldehyde-QDs with 2-hydrazinopyridine (2-HP). This covalent modification produces QD-conjugates with a well-defined absorption feature at 350 nm ascribed to the hydrazone chromophore. We exploited this unique optical signature to accurately measure the number of aldehyde groups per QD when the fraction of LA-PEG-CHO per nanocrystal was varied. This allowed us to extract an estimate for the number of LA-PEG ligands per QD. These results suggest that hydrazone ligation has the potential to provide a simple and general analytical method to estimate the number of surface ligands for a variety of nanocrystals such as metal, metal oxide and semiconductor nanocrystals.

Effects of macromolecular crowding on the structure of a protein complex: A small-angle scattering study of superoxide dismutase

DOE PAGES

Rajapaksha, Ajith; Stanley, Christopher B.; Todd, Brian A.

2015-02-17

Macromolecular crowding can alter the structure and function of biological macromolecules. We used small angle scattering (SAS) to measure the change in size of a protein complex, superoxide dismutase (SOD), induced by macromolecular crowding. Crowding was induced using 400 MW polyethylene glycol (PEG), triethylene glycol (TEG), methyl- -glucoside ( -MG) and trimethylamine N-oxide (TMAO). Parallel small angle neutron scattering (SANS) and small angle x-ray scattering (SAXS) allowed us to unambiguously attribute apparent changes in radius of gyration to changes in the structure of SOD. For a 40% PEG solution, we find that the volume of SOD was reduced by 9%.more » Considering the osmotic pressure due to PEG, this deformation corresponds to a highly compressible structure. SAXS done in the presence of TEG suggests that for further deformation beyond a 9% decrease in volume the resistance to deformation may increase dramatically.« less

Chemical Interactions of Polyethylene Glycols (PEG) and Glycerol with Protein Functional Groups: Applications to PEG, Glycerol Effects on Protein Processes

PubMed Central

Knowles, DB; Shkel, Irina A; Phan, Noel M; Sternke, Matt; Lingeman, Emily; Cheng, Xian; Cheng, Lixue; O’Connor, Kevin; Record, M. Thomas

2015-01-01

Here we obtain the data needed to predict chemical interactions of polyethylene glycols (PEGs) and glycerol with proteins and related organic compounds, and thereby interpret or predict chemical effects of PEGs on protein processes. To accomplish this we determine interactions of glycerol and tetraEG with >30 model compounds displaying the major C, N, and O functional groups of proteins. Analysis of these data yields coefficients (α-values) quantifying interactions of glycerol, tetraEG and PEG end (-CH2OH) and interior (-CH2OCH2-) groups with these groups, relative to interactions with water. TetraEG (strongly) and glycerol (weakly) interact favorably with aromatic C, amide N, and cationic N, but unfavorably with amide O, carboxylate O and salt ions. Strongly unfavorable O and salt anion interactions help make both small and large PEGs effective protein precipitants. Interactions of tetraEG and PEG interior groups with aliphatic C are quite favorable, while interactions of glycerol and PEG end groups with aliphatic C are not. Hence tetraEG and PEG 300 favor unfolding of the DNA-binding domain of lac repressor (lacDBD) while glycerol, di- and mono-ethylene glycol are stabilizers. Favorable interactions with aromatic and aliphatic C explain why PEG400 greatly increases the solubility of aromatic hydrocarbons and steroids. PEG400-steroid interactions are unusually favorable, presumably because of simultaneous interactions of multiple PEG interior groups with the fused ring system of the steroid. Using α-values reported here, chemical contributions to PEG m-values can be predicted or interpreted in terms of changes in water-accessible surface area (ΔASA), and separated from excluded volume effects. PMID:25962980

Kinetic Assembly of Near-IR Active Gold Nanoclusters using Weakly Adsorbing Polymers to Control Size

PubMed Central

Tam, Jasmine M.; Murthy, Avinash K.; Ingram, Davis R.; Nguyen, Robin; Sokolov, Konstantin V.; Johnston, Keith P.

2013-01-01

Clusters of metal nanoparticles with an overall size less than 100 nm and high metal loadings for strong optical functionality, are of interest in various fields including microelectronics, sensors, optoelectronics and biomedical imaging and therapeutics. Herein we assemble ~5 nm gold particles into clusters with controlled size, as small as 30 nm and up to 100 nm, which contain only small amounts of polymeric stabilizers. The assembly is kinetically controlled with weakly adsorbing polymers, PLA(2K)-b-PEG(10K)-b-PLA(2K) or PEG (MW = 3350), by manipulating electrostatic, van der Waals (VDW), steric, and depletion forces. The cluster size and optical properties are tuned as a function of particle volume fractions and polymer/gold ratios to modulate the interparticle interactions. The close spacing between the constituent gold nanoparticles and high gold loadings (80–85% w/w gold) produce a strong absorbance cross section of ~9×10−15 m2 in the NIR at 700 nm. This morphology results from VDW and depletion attractive interactions that exclude the weakly adsorbed polymeric stabilizer from the cluster interior. The generality of this kinetic assembly platform is demonstrated for gold nanoparticles with a range of surface charges from highly negative to neutral, with the two different polymers. PMID:20361735

Effects of cold plasma treatment on alfalfa seed growth under simulated drought stress

NASA Astrophysics Data System (ADS)

Jinkui, FENG; Decheng, WANG; Changyong, SHAO; Lili, ZHANG; Xin, TANG

2018-03-01

The effect of different cold plasma treatments on the germination and seedling growth of alfalfa (Medicago sativa L.) seeds under simulated drought stress conditions was investigated. Polyethyleneglycol-6000 (PEG 6000)with the mass fraction of 0% (purified water), 5%, 10%, and 15% were applied to simulate the drought environment. The alfalfa seeds were treated with 15 different power levels ranged between 0-280 W for 15 s. The germination potential, germination rate, germination index, seedling root length, seedling height, and vigor index were investigated. Results indicated significant differences between treated with proper power and untreated alfalfa seeds. With the increase of treatment power, these indexes mentioned above almost presented bimodal curves. Under the different mass fractions of PEG 6000, results showed that the lower power led to increased germination, and the seedlings presented good adaptability to different drought conditions. Meanwhile, higher power levels resulted in a decreased germination rate. Seeds treated with 40 W resulted in higher germination potential, germination rate, seedling height, root length, and vigor index. Vigor indexes of the treated seeds under different PEG 6000 stresses increased by 38.68%, 43.91%, 74.34%, and 39.20% respectively compared to CK0-0, CK5-0, CK10-0, and CK15-0 (the control sample under 0%, 5%, 10%, and 15% PEG 6000). Therefore, 40 W was regarded as the best treatment in this research. Although the trend indexes of alfalfa seeds treated with the same power were statistically the same under different PEG 6000 stresses, the cold plasma treatment had a significant effect on the adaptability of alfalfa seeds in different drought environments. Thus, this kind of treatment is worth implementing to promote seed growth under drought situations.

Preparation and in vivo evaluation of multifunctional ⁹⁰Y-labeled magnetic nanoparticles designed for cancer therapy.

PubMed

Radović, Magdalena; Calatayud, María Pilar; Goya, Gerardo Fabián; Ibarra, Manuel Ricardo; Antić, Bratislav; Spasojević, Vojislav; Nikolić, Nadežda; Janković, Drina; Mirković, Marija; Vranješ-Đurić, Sanja

2015-01-01

Two different types of magnetic nanoparticles (MNPs) were synthesized in order to compare their efficiency as radioactive vectors, Fe₃O₄-Naked (80 ± 5 nm) and polyethylene glycol 600 diacid functionalized Fe₃O₄(Fe₃O₄-PEG600) MNPs (46 ± 0.6 nm). They were characterized based on the external morphology, size distribution, and colloidal and magnetic properties. The obtained specific power absorption value for Fe₃O₄-PEG600 MNPs was 200 W/g, indicated their potential in hyperthermia based cancer treatments. The labeling yield, in vitro stability and in vivo biodistribution profile of (90) Y-MNPs were compared. Both types of MNPs were (90)Y-labeled in reproducible high yield (>97%). The stability of the obtained radioactive nanoparticles was evaluated in saline and human serum media in order to optimize the formulations for in vivo use. The biodistribution in Wistar rats showed different pharmacokinetic behaviors of nanoparticles: a large fraction of both injected MNPs ended in the liver (14.58%ID/g for (90)Y-Fe₃O₄-Naked MNPs and 19.61%ID/g for (90)Y-Fe₃O₄-PEG600 MNPs) whereas minor fractions attained in other organs. The main difference between the two types of MNPs was the higher accumulation of (90)Y-Fe₃O₄-Naked MNPs in the lungs (12.14%ID/g vs. 2.00%ID/g for (90)Y-Fe₃O₄-PEG600 MNPs) due to their in vivo agglomeration. The studied radiolabeled magnetic complexes such as (90)Y-Fe₃O₄-PEG600 MNPs constitute a great promise for multiple diagnostic-therapeutic uses combining, for example, MRI-magnetic hyperthermia and regional radiotherapy. © 2014 Wiley Periodicals, Inc.

Preparation and thermal properties of mineral-supported polyethylene glycol as form-stable composite phase change materials (CPCMs) used in asphalt pavements.

PubMed

Jin, Jiao; Lin, Feipeng; Liu, Ruohua; Xiao, Ting; Zheng, Jianlong; Qian, Guoping; Liu, Hongfu; Wen, Pihua

2017-12-05

Three kinds of mineral-supported polyethylene glycol (PEG) as form-stable composite phase change materials (CPCMs) were prepared to choose the most suitable CPCMs in asphalt pavements for the problems of asphalt pavements rutting diseases and urban heat islands. The microstructure and chemical structure of CPCMs were characterized by SEM, FT-IR and XRD. Thermal properties of the CPCMs were determined by TG and DSC. The maximum PEG absorption of diatomite (DI), expanded perlite (EP) and expanded vermiculite (EVM) could reach 72%, 67% and 73.6%, respectively. The melting temperatures and latent heat of CPCMs are in the range of 52-55 °C and 100-115 J/g, respectively. The results show that PEG/EP has the best thermal and chemical stability after 100 times of heating-cooling process. Moreover, crystallization fraction results show that PEG/EP has slightly higher latent heats than that of PEG/DI and PEG/EVM. Temperature-adjusting asphalt mixture was prepared by substituting the fine aggregates with PEG/EP CPCMs. The upper surface maximum temperature difference of temperature-adjusting asphalt mixture reaches about 7.0 °C in laboratory, and the surface peak temperature reduces up to 4.3 °C in the field experiment during a typical summer day, indicating a great potential application for regulating pavement temperature field and alleviating the urban heat islands.

Period of an Interrupted Pendulum

NASA Astrophysics Data System (ADS)

Miller, Bradley E.

2002-11-01

While demonstrating a classic conservation-of-energy problem to my AP Physics students, I became curious about the periodic motion that ensued for certain initial conditions. The original problem consists of releasing a mass at the end of a string from an initial position horizontal to the plane of a table. The string comes in contact with a peg some distance below the point where the string is attached at the top. One is asked to find what minimum fraction of the string's length should the peg be placed to have the mass complete a circle about the peg. However, when the mass is released from much lower heights, the system undergoes periodic motion that can be thought of as an interrupted pendulum.

Evaluation of the biocompatibility of a coating material for an implantable bladder volume sensor.

PubMed

Kim, Su-Jin; Lee, Dong-Sup; Kim, In-Gul; Sohn, Dong-Wan; Park, Jung-Yul; Choi, Bum-Kyoo; Kim, Sae-Woong

2012-03-01

As the applications for implantable medical devices have increased, the need for biocompatible packaging materials has become important. Recently, we reported an implantable sensor for real-time monitoring of the changes in bladder volume, which necessitated finding a safe coating material for use in bladder tissue. At present, materials like polyethylene glycol (PEG), polydimethylsiloxane (PDMS) and parylene-C are used in biomedical devices or as coating materials, owing to their excellent safety in various medical fields. However, few studies have assessed their safety in bladder tissue, therefore, we evaluated the biocompatibility of PEG, PDMS and parylene-C in the bladder. All three materials turned out to be safe in in vitro tests of live/dead staining and cell viability. In vivo tests with hematoxylin and eosin and immunofluorescence staining with MAC387 showed no persistent inflammation. Therefore, we consider that the three materials are biocompatible in bladder tissue. Despite this safety, however, PEG has biodegradable characteristics and thus is not suitable for use as packaging. We suggest that PDMS and parylene-C can be used as safe coating materials for the implantable bladder volume sensor reported previously. Copyright © 2012. Published by Elsevier B.V.

Downstream processing of antibodies: single-stage versus multi-stage aqueous two-phase extraction.

PubMed

Rosa, P A J; Azevedo, A M; Ferreira, I F; Sommerfeld, S; Bäcker, W; Aires-Barros, M R

2009-12-11

Single-stage and multi-stage strategies have been evaluated and compared for the purification of human antibodies using liquid-liquid extraction in aqueous two-phase systems (ATPSs) composed of polyethylene glycol 3350 (PEG 3350), dextran, and triethylene glycol diglutaric acid (TEG-COOH). The performance of single-stage extraction systems was firstly investigated by studying the effect of pH, TEG-COOH concentration and volume ratio on the partitioning of the different components of a Chinese hamster ovary (CHO) cells supernatant. It was observed that lower pH values and high TEG-COOH concentrations favoured the selective extraction of human immunoglobulin G (IgG) to the PEG-rich phase. Higher recovery yields, purities and percentage of contaminants removal were always achieved in the presence of the ligand, TEG-COOH. The extraction of IgG could be enhanced using higher volume ratios, however with a significant decrease in both purity and percentage of contaminants removal. The best single-stage extraction conditions were achieved for an ATPS containing 1.3% (w/w) TEG-COOH with a volume ratio of 2.2, which allowed the recovery of 96% of IgG in the PEG-rich phase with a final IgG concentration of 0.21mg/mL, a protein purity of 87% and a total purity of 43%. In order to enhance simultaneously both recovery yield and purity, a four stage cross-current operation was simulated and the corresponding liquid-liquid equilibrium (LLE) data determined. A predicted optimised scheme of a counter-current multi-stage aqueous two-phase extraction was hence described. IgG can be purified in the PEG-rich top phase with a final recovery yield of 95%, a final concentration of 1.04mg/mL and a protein purity of 93%, if a PEG/dextran ATPS containing 1.3% (w/w) TEG-COOH, 5 stages and volume ratio of 0.4 are used. Moreover, according to the LLE data of all CHO cells supernatant components, it was possible to observe that most of the cells supernatant contaminants can be removed during this extraction step leading to a final total purity of about 85%.

Concentration dependence of lipopolymer self-diffusion in supported bilayer membranes

PubMed Central

Zhang, Huai-Ying; Hill, Reghan J.

2011-01-01

Self-diffusion coefficients of poly(ethylene glycol)2k-derivatized lipids (DSPE-PEG2k-CF) in glass-supported DOPC phospholipid bilayers are ascertained from quantitative fluorescence recovery after photobleaching (FRAP). We developed a first-order reaction–diffusion model to ascertain the bleaching constant, mobile fraction and lipopolymer self-diffusion coefficient Ds at concentrations in the range c ≈ 0.5–5 mol%. In contrast to control experiments with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(7-nitro-2-1,3-benzoxadiazol-4-yl) (ammonium salt) (DOPE-NBD) in 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), the lipopolymer self-diffusion coefficient decreases monotonically with increasing concentration, without a distinguishing mushroom-to-brush transition. Our data yield a correlation Ds = D0/(1 + αc), where D0 ≈ 3.36 µm2 s−1 and α ≈ 0.56 (with c expressed as a mole percent). Interpreting the dilute limit with the Scalettar–Abney–Owicki statistical mechanical theory for transmembrane proteins yields an effective disc radius ae ≈ 2.41 nm. On the other hand, the Bussell–Koch–Hammer theory, which includes hydrodynamic interactions, yields ae ≈ 2.92 nm. As expected, both measures are smaller than the Flory radius of the 2 kDa poly(ethylene glycol) (PEG) chains, RF ≈ 3.83 nm, and significantly larger than the nominal radius of the phospholipid heads, al ≈ 0.46 nm. The diffusion coefficient at infinite dilution D0 was interpreted using the Evans–Sackmann theory, furnishing an inter-leaflet frictional drag coefficient bs ≈ 1.33 × 108 N s m−3. Our results suggest that lipopolymer interactions are dominated by the excluded volume of the PEG-chain segments, with frictional drag dominated by the two-dimensional bilayer hydrodynamics. PMID:20504804

High-molecular-weight polyethylene glycol inhibits myocardial ischemia-reperfusion injury in vivo.

PubMed

Xu, Xianyao; Philip, Jennifer L; Razzaque, Md Abdur; Lloyd, James W; Muller, Charlie M; Akhter, Shahab A

2015-02-01

Cardiac ischemia-reperfusion (I-R) injury remains a significant problem as there are no therapies available to minimize the cell death that can lead to impaired function and heart failure. We have shown that high-molecular-weight polyethylene glycol (PEG) (15-20 kD) can protect cardiac myocytes in vitro from hypoxia-reoxygenation injury. In this study, we investigated the potential protective effects of PEG in vivo. Adult rats underwent left anterior descending artery occlusion for 60 minutes followed by 48 hours or 4 weeks of reperfusion. One milliliter of 10% PEG solution or phosphate-buffered saline (PBS) control (n = 10 per group) was administered intravenously (IV) immediately before reperfusion. Fluorescein-labeled PEG was robustly visualized in the myocardium 1 hour after IV delivery. The PEG group had significant recovery of left ventricular ejection fraction at 4 weeks versus a 25% decline in the PBS group (P < .01). There was 50% less LV fibrosis in the PEG group versus PBS with smaller peri-infarct and remote territory fibrosis (P < .01). Cell survival signaling was upregulated in the PEG group with increased Akt (3-fold, P < .01) and ERK (4-fold, P < .05) phosphorylation compared to PBS controls at 48 hours. PEG also inhibited apoptosis as measured by TUNEL-positive nuclei (56% decrease, P < .02) and caspase 3 activity (55% decrease, P < .05). High-molecular-weight PEG appears to have a significant protective effect from I-R injury in the heart when administered IV immediately before reperfusion. This may have important clinical translation in the setting of acute coronary revascularization and myocardial protection in cardiac surgery. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Small volume isosmotic polyethylene glycol electrolyte balanced solution (PMF-100) in treatment of chronic nonorganic constipation.

PubMed

Corazziari, E; Badiali, D; Habib, F I; Reboa, G; Pitto, G; Mazzacca, G; Sabbatini, F; Galeazzi, R; Cilluffo, T; Vantini, I; Bardelli, E; Baldi, F

1996-08-01

The present multicenter double-blind placebo-controlled trial evaluates the therapeutic effectiveness of small-volume daily doses of an isosmotic polyethylene glycol (PEG) electrolyte solution in the treatment of chronic nonorganic constipation. After a complete diagnostic investigation, patients still constipated at the end of a four-week placebo-treatment run-in period were enrolled and randomized to receive either placebo or PEG solution 250 ml twice a day for the following eight weeks. Patients were assessed at four and eight weeks of treatment, and they reported frequency and modality of evacuation, use of laxatives, and relevant symptoms daily on a diary card. Oroanal and segmental large-bowel transit times were assessed with radiopaque markers during the fourth week of the run-in period and the last week of the treatment period. During the study period, dietary fiber and liquids were standardized and laxatives were allowed only after five consecutive days without a bowel movement. Of the 55 patients enrolled, five dropped out, three because of adverse events and two for reasons unrelated to therapy; another two were excluded from the efficacy analysis because of protocol violation. Of the remaining 48 patients (37 women, age 42 +/- 15 years, mean +/- SD), 23 were assigned to placebo and 25 to PEG treatment. In comparison to placebo, PEG solution induced a statistically significant increase in weekly bowel frequency at four weeks and at the end of the study (PEG: 4.8 +/- 2.3 vs placebo: 2.8 +/- 1.6; P < 0.002) and a significant decrease in straining at defecation (P < 0.01), stool consistency (P < 0.02), and use of laxatives (P < 0.03). Oroanal, left colon, and rectal transit times were significantly shortened by PEG treatment. There was no difference between controls and PEG-treated patients as far as abdominal symptoms and side effects were concerned. In conclusion, PEG solution at 250 ml twice a day is effective in increasing bowel frequency, accelerating colorectal transit times, and improving difficult evacuation in patients with chronic nonorganic constipation and is devoid of significant side effects.

Bursting Bubbles and Bilayers

PubMed Central

Wrenn, Steven P.; Dicker, Stephen M.; Small, Eleanor F.; Dan, Nily R.; Mleczko, Michał; Schmitz, Georg; Lewin, Peter A.

2012-01-01

This paper discusses various interactions between ultrasound, phospholipid monolayer-coated gas bubbles, phospholipid bilayer vesicles, and cells. The paper begins with a review of microbubble physics models, developed to describe microbubble dynamic behavior in the presence of ultrasound, and follows this with a discussion of how such models can be used to predict inertial cavitation profiles. Predicted sensitivities of inertial cavitation to changes in the values of membrane properties, including surface tension, surface dilatational viscosity, and area expansion modulus, indicate that area expansion modulus exerts the greatest relative influence on inertial cavitation. Accordingly, the theoretical dependence of area expansion modulus on chemical composition - in particular, poly (ethylene glyclol) (PEG) - is reviewed, and predictions of inertial cavitation for different PEG molecular weights and compositions are compared with experiment. Noteworthy is the predicted dependence, or lack thereof, of inertial cavitation on PEG molecular weight and mole fraction. Specifically, inertial cavitation is predicted to be independent of PEG molecular weight and mole fraction in the so-called mushroom regime. In the “brush” regime, however, inertial cavitation is predicted to increase with PEG mole fraction but to decrease (to the inverse 3/5 power) with PEG molecular weight. While excellent agreement between experiment and theory can be achieved, it is shown that the calculated inertial cavitation profiles depend strongly on the criterion used to predict inertial cavitation. This is followed by a discussion of nesting microbubbles inside the aqueous core of microcapsules and how this significantly increases the inertial cavitation threshold. Nesting thus offers a means for avoiding unwanted inertial cavitation and cell death during imaging and other applications such as sonoporation. A review of putative sonoporation mechanisms is then presented, including those involving microbubbles to deliver cargo into a cell, and those - not necessarily involving microubbles - to release cargo from a phospholipid vesicle (or reverse sonoporation). It is shown that the rate of (reverse) sonoporation from liposomes correlates with phospholipid bilayer phase behavior, liquid-disordered phases giving appreciably faster release than liquid-ordered phases. Moreover, liquid-disordered phases exhibit evidence of two release mechanisms, which are described well mathematically by enhanced diffusion (possibly via dilation of membrane phospholipids) and irreversible membrane disruption, whereas liquid-ordered phases are described by a single mechanism, which has yet to be positively identified. The ability to tune release kinetics with bilayer composition makes reverse sonoporation of phospholipid vesicles a promising methodology for controlled drug delivery. Moreover, nesting of microbubbles inside vesicles constitutes a truly “theranostic” vehicle, one that can be used for both long-lasting, safe imaging and for controlled drug delivery. PMID:23382772

Bursting bubbles and bilayers.

PubMed

Wrenn, Steven P; Dicker, Stephen M; Small, Eleanor F; Dan, Nily R; Mleczko, Michał; Schmitz, Georg; Lewin, Peter A

2012-01-01

This paper discusses various interactions between ultrasound, phospholipid monolayer-coated gas bubbles, phospholipid bilayer vesicles, and cells. The paper begins with a review of microbubble physics models, developed to describe microbubble dynamic behavior in the presence of ultrasound, and follows this with a discussion of how such models can be used to predict inertial cavitation profiles. Predicted sensitivities of inertial cavitation to changes in the values of membrane properties, including surface tension, surface dilatational viscosity, and area expansion modulus, indicate that area expansion modulus exerts the greatest relative influence on inertial cavitation. Accordingly, the theoretical dependence of area expansion modulus on chemical composition-- in particular, poly (ethylene glyclol) (PEG)--is reviewed, and predictions of inertial cavitation for different PEG molecular weights and compositions are compared with experiment. Noteworthy is the predicted dependence, or lack thereof, of inertial cavitation on PEG molecular weight and mole fraction. Specifically, inertial cavitation is predicted to be independent of PEG molecular weight and mole fraction in the so-called mushroom regime. In the "brush" regime, however, inertial cavitation is predicted to increase with PEG mole fraction but to decrease (to the inverse 3/5 power) with PEG molecular weight. While excellent agreement between experiment and theory can be achieved, it is shown that the calculated inertial cavitation profiles depend strongly on the criterion used to predict inertial cavitation. This is followed by a discussion of nesting microbubbles inside the aqueous core of microcapsules and how this significantly increases the inertial cavitation threshold. Nesting thus offers a means for avoiding unwanted inertial cavitation and cell death during imaging and other applications such as sonoporation. A review of putative sonoporation mechanisms is then presented, including those involving microbubbles to deliver cargo into a cell, and those--not necessarily involving microubbles--to release cargo from a phospholipid vesicle (or reverse sonoporation). It is shown that the rate of (reverse) sonoporation from liposomes correlates with phospholipid bilayer phase behavior, liquid-disordered phases giving appreciably faster release than liquid-ordered phases. Moreover, liquid-disordered phases exhibit evidence of two release mechanisms, which are described well mathematically by enhanced diffusion (possibly via dilation of membrane phospholipids) and irreversible membrane disruption, whereas liquid-ordered phases are described by a single mechanism, which has yet to be positively identified. The ability to tune release kinetics with bilayer composition makes reverse sonoporation of phospholipid vesicles a promising methodology for controlled drug delivery. Moreover, nesting of microbubbles inside vesicles constitutes a truly "theranostic" vehicle, one that can be used for both long-lasting, safe imaging and for controlled drug delivery.

Use of Powder PEG-3350 as a Sole Bowel Preparation: Clinical Case Series of 245 Patients.

PubMed

Arora, Manish; Okolo, Patrick I

2008-07-01

To assess the efficacy of low-volume powder polyethylene glycol (PEG)-3350 as a sole bowel preparation for colonoscopy. This case series examined 245 consecutive patients (a mixture of inpatients and outpatients undergoing screening colonoscopy) at a hospital endoscopy center over a 2-year period. The patients received powder PEG-3350 in the amount of 204 g dissolved in 32 oz of water and taken in 3 divided doses 1 hour apart with 8 oz of water in between each dose. Colon preparation scores (CPS) were used to assess the quality of colon cleansing. The results obtained from the 245 patients were collated and compared to those of patients receiving sodium phosphate, the historical control. The mean CPS was calculated to be 3.43, with a standard deviation of 1.12. Of the 245 patients, 92 were scored with a grade of 4, and 5 patients had incomplete colonoscopies secondary to failure of bowel preparation (CPS=0). Among the remaining patients, 22 and 26 were graded as poor (CPS=1) or fair (CPS=2) bowel preparations, respectively. The low-volume powder PEG-3350 formula used in our case series showed effective colon cleansing and may be considered for use as a sole bowel preparation.

Use of Powder PEG-3350 as a Sole Bowel Preparation

PubMed Central

Arora, Manish

2008-01-01

Objective: To assess the efficacy of low-volume powder polyethylene glycol (PEG)-3350 as a sole bowel preparation for colonoscopy. Methods: This case series examined 245 consecutive patients (a mixture of inpatients and outpatients undergoing screening colonoscopy) at a hospital endoscopy center over a 2-year period. The patients received powder PEG-3350 in the amount of 204 g dissolved in 32 oz of water and taken in 3 divided doses 1 hour apart with 8 oz of water in between each dose. Colon preparation scores (CPS) were used to assess the quality of colon cleansing. The results obtained from the 245 patients were collated and compared to those of patients receiving sodium phosphate, the historical control. Results: The mean CPS was calculated to be 3.43, with a standard deviation of 1.12. Of the 245 patients, 92 were scored with a grade of 4, and 5 patients had incomplete colonoscopies secondary to failure of bowel preparation (CPS=0). Among the remaining patients, 22 and 26 were graded as poor (CPS=1) or fair (CPS=2) bowel preparations, respectively. Conclusion: The low-volume powder PEG-3350 formula used in our case series showed effective colon cleansing and may be considered for use as a sole bowel preparation. PMID:21960925

Enhanced the performance of graphene oxide/polyimide hybrid membrane for CO2 separation by surface modification of graphene oxide using polyethylene glycol

NASA Astrophysics Data System (ADS)

Wu, Li-guang; Yang, Cai-hong; Wang, Ting; Zhang, Xue-yang

2018-05-01

Polyethylene glycol (PEG) with different molecular weights was first used to modify graphene oxide (GO) samples. Subsequently, polyimide (PI) hybrid membranes containing modified-GO were fabricated via in situ polymerization. The separation performance of these hybrid membranes was evaluated using permeation experiments for CO2 and N2 gases. The morphology characterization showed that PEG with suitable molecular weight could be successfully grafted on the GO surface. PEG modification altered the surface properties of GO and introduced defective structures onto GO surface. This caused strong surface polarity and high free volume of membranes containing PEG-modified GO, thereby improving the separation performance of membranes. The addition of PEG-GO with low molecular weight effectively increased gas diffusion through hybrid membranes. The hybrid membranes containing PEG-GO with large molecular weight had high solubility performance for CO2 gas due to the introduction of numerous polar groups into polymeric membranes. With the loading content of modified GO, the CO2 gas permeability of hybrid membranes initially increased but eventually decreased. The optimal content of modified GO in membranes reached 3.0 wt%. When too much PEG added (exceeding 30 g), some impurities formed on GO surface and some aggregates appeared in the resulting hybrid membrane, which depressed the membrane performance.

A dual-action, low-volume bowel cleanser administered the day before colonoscopy: results from the SEE CLEAR II study.

PubMed

Katz, Philip O; Rex, Douglas K; Epstein, Michael; Grandhi, Nav K; Vanner, Stephen; Hookey, Lawrence C; Alderfer, Vivian; Joseph, Raymond E

2013-03-01

Optimal bowel preparation is vital for the efficacy and safety of colonoscopy. The inconvenience, discomfort, required consumption of large volumes of product, and potential adverse effects associated with some bowel preparations deter patients from colonoscopy and may provide inadequate cleansing. A dual-action, non-phosphate, natural orange-flavored, low-volume preparation containing sodium picosulfate and magnesium citrate (P/MC) is currently being reviewed for bowel cleansing. This was a phase 3, randomized, multicenter, assessor-blinded, prespecified non-inferiority, head-to-head study to investigate the efficacy, safety, and tolerability of day-before administration of P/MC vs. 2L polyethylene glycol solution and two 5-mg bisacodyl tablets (2L PEG-3350 and bisacodyl tablets (HalfLytely and Bisacodyl Tablets Bowel Prep Kit)) in adult patients preparing for colonoscopy (SEE CLEAR II Study). The primary objective of the study was to demonstrate the non-inferiority of P/MC to 2L PEG-3350 and bisacodyl tablets in overall colon cleansing using a modified Aronchick scale. In addition, efficacy in the ascending, mid (transverse and descending), and recto-sigmoid segments of colon was evaluated using a modified Ottawa scale. Patient acceptability and tolerability of the bowel preparations were assessed via a standard questionnaire. Safety was assessed based on the monitoring of adverse events (AEs) and meaningful findings on clinical evaluations including physical examinations, vital sign measurements, and electrocardiograms (ECGs). A total of 603 patients were randomized to receive either P/MC (n = 300) or 2L PEG-3350 and bisacodyl tablets (n = 303). Based on the Aronchick scale, successful overall cleansing was similar in patients receiving P/MC (83.0%) and patients receiving 2L PEG-3350 and bisacodyl tablets (79.7%). P/MC demonstrated non-inferiority to 2L PEG-3350 and bisacodyl tablets in overall cleansing of the colon, as measured by the Aronchick scale. Similarly, the efficacy of P/MC, as measured by the Ottawa scale, was non-inferior to 2L PEG-3350 and bisacodyl tablets in cleansing the ascending, mid, and recto-sigmoid segments of the colon. Patient-reported acceptability and tolerability for each item examined on the questionnaire was significantly greater for P/MC compared with 2L PEG-3350 and bisacodyl tablets (P<0.0001).Treatment-emergent AEs related to the bowel preparation reported by 1% of patients receiving P/MC or 2L PEG-3350 and bisacodyl tablets were nausea (3.0% vs. 4.3%), vomiting (1.4% vs. 2.0%), and headache (2.7% vs. 1.7%). No clinically meaningful changes were noted in either treatment arm in data collected from physical examinations, vital sign measurements, and ECGs. When administered as a day-before dose, the bowel cleansing effects of P/MC were non-inferior compared with 2L PEG-3350 and bisacodyl tablets using the clinician-rated Aronchick and Ottawa scales. Treatment acceptability was significantly more favorable in patients receiving P/MC than in patients receiving 2L PEG-3350 and bisacodyl tablets.

Predictors of laparoscopic simulation performance among practicing obstetrician gynecologists.

PubMed

Mathews, Shyama; Brodman, Michael; D'Angelo, Debra; Chudnoff, Scott; McGovern, Peter; Kolev, Tamara; Bensinger, Giti; Mudiraj, Santosh; Nemes, Andreea; Feldman, David; Kischak, Patricia; Ascher-Walsh, Charles

2017-11-01

While simulation training has been established as an effective method for improving laparoscopic surgical performance in surgical residents, few studies have focused on its use for attending surgeons, particularly in obstetrics and gynecology. Surgical simulation may have a role in improving and maintaining proficiency in the operating room for practicing obstetrician gynecologists. We sought to determine if parameters of performance for validated laparoscopic virtual simulation tasks correlate with surgical volume and characteristics of practicing obstetricians and gynecologists. All gynecologists with laparoscopic privileges (n = 347) from 5 academic medical centers in New York City were required to complete a laparoscopic surgery simulation assessment. The physicians took a presimulation survey gathering physician self-reported characteristics and then performed 3 basic skills tasks (enforced peg transfer, lifting/grasping, and cutting) on the LapSim virtual reality laparoscopic simulator (Surgical Science Ltd, Gothenburg, Sweden). The association between simulation outcome scores (time, efficiency, and errors) and self-rated clinical skills measures (self-rated laparoscopic skill score or surgical volume category) were examined with regression models. The average number of laparoscopic procedures per month was a significant predictor of total time on all 3 tasks (P = .001 for peg transfer; P = .041 for lifting and grasping; P < .001 for cutting). Average monthly laparoscopic surgical volume was a significant predictor of 2 efficiency scores in peg transfer, and all 4 efficiency scores in cutting (P = .001 to P = .015). Surgical volume was a significant predictor of errors in lifting/grasping and cutting (P < .001 for both). Self-rated laparoscopic skill level was a significant predictor of total time in all 3 tasks (P < .0001 for peg transfer; P = .009 for lifting and grasping; P < .001 for cutting) and a significant predictor of nearly all efficiency scores and errors scores in all 3 tasks. In addition to total time, there was at least 1 other objective performance measure that significantly correlated with surgical volume for each of the 3 tasks. Higher-volume physicians and those with fellowship training were more confident in their laparoscopic skills. By determining simulation performance as it correlates to active physician practice, further studies may help assess skill and individualize training to maintain skill levels as case volumes fluctuate. Copyright © 2017 Elsevier Inc. All rights reserved.

Poly(ethylene glycol)s in Semidilute Regime: Radius of Gyration in the Bulk and Partitioning into a Nanopore

DOE PAGES

Gurnev, Philip A.; Stanley, Christopher B.; Aksoyoglu, M. Alphan; ...

2017-03-09

In this work, using two approaches, small-angle neutron scattering (SANS) from bulk solutions and nanopore conductance-fluctuation analysis, we studied structural and dynamic features of poly(ethylene glycol) (PEG) water/salt solutions in the dilute and semidilute regimes. SANS measurements on PEG 3400 at the zero-average contrast yielded the single chain radius of gyration (R g) over 1–30 wt %. We observed a small but statistically reliable decrease in R g with increasing PEG concentration: at 30 wt % the chain contracts by a factor of 0.94. Analyzing conductance fluctuations of the α-hemolysin nanopore in the mixtures of PEG 200 with PEG 3400,more » we demonstrated that polymer partitioning into the nanopore is mostly due to PEG 200. Specifically, for a 1:1 wt/wt mixture the smaller polymer dominates to the extent that only about 1/25 of the nanopore volume is taken by the larger polymer. In conclusion, these findings advance our conceptual and quantitative understanding of nanopore polymer partitioning; they also support the main assumptions of the recent “polymers-pushing-polymers” model.« less

Stabilization of Resveratrol in Blood Circulation by Conjugation to mPEG and mPEG-PLA Polymers: Investigation of Conjugate Linker and Polymer Composition on Stability, Metabolism, Antioxidant Activity and Pharmacokinetic Profile

PubMed Central

Siddalingappa, Basavaraj; Benson, Heather A. E.; Brown, David H.; Batty, Kevin T.; Chen, Yan

2015-01-01

Resveratrol is naturally occurring phytochemical with diverse biological activities such as chemoprevention, anti-inflammatory, anti-cancer, anti-oxidant. But undergoes rapid metabolism in the body (half life 0.13h). Hence Polymer conjugation utilizing different chemical linkers and polymer compositions was investigated for enhanced pharmacokinetic profile of resveratrol. Ester conjugates such as α-methoxy-ω-carboxylic acid poly(ethylene glycol) succinylamide resveratrol (MeO-PEGN-Succ-RSV) (2 and 20 kDa); MeO-PEG succinyl ester resveratrol (MeO-PEGO-Succ-RSV) (2 kDa); α-methoxy poly(ethylene glycol)-co-polylactide succinyl ester resveratrol (MeO-PEG-PLAO-Succ-RSV) (2 and 6.6kDa) were prepared by carbodiimide coupling reactions. Resveratrol-PEG ethers (2 and 5 kDa) were synthesized by alkali-mediated etherification. All polymer conjugates were fully characterized in vitro and the pharmacokinetic profile of selected conjugates was characterized in rats. Buffer and plasma stability of conjugates was dependent on polymer hydrophobicity, aggregation behavior and PEG corona, with MeO-PEG-PLAO-Succ-RSV (2 kDa) showing a 3h half-life in rat plasma in vitro. Polymer conjugates irrespective of linker chemistry protected resveratrol against metabolism in vitro. MeO-PEG-PLAO-Succ-RSV (2 kDa), Resveratrol-PEG ether (2 and 5 kDa) displayed improved pharmacokinetic profiles with significantly higher plasma area under curve (AUC), slower clearance and smaller volume of distribution, compared to resveratrol. PMID:25799413

A scanning transmission electron microscopy approach to analyzing large volumes of tissue to detect nanoparticles.

PubMed

Kempen, Paul J; Thakor, Avnesh S; Zavaleta, Cristina; Gambhir, Sanjiv S; Sinclair, Robert

2013-10-01

The use of nanoparticles for the diagnosis and treatment of cancer requires the complete characterization of their toxicity, including accurately locating them within biological tissues. Owing to their size, traditional light microscopy techniques are unable to resolve them. Transmission electron microscopy provides the necessary spatial resolution to image individual nanoparticles in tissue, but is severely limited by the very small analysis volume, usually on the order of tens of cubic microns. In this work, we developed a scanning transmission electron microscopy (STEM) approach to analyze large volumes of tissue for the presence of polyethylene glycol-coated Raman-active-silica-gold-nanoparticles (PEG-R-Si-Au-NPs). This approach utilizes the simultaneous bright and dark field imaging capabilities of STEM along with careful control of the image contrast settings to readily identify PEG-R-Si-Au-NPs in mouse liver tissue without the need for additional time-consuming analytical characterization. We utilized this technique to analyze 243,000 mm³ of mouse liver tissue for the presence of PEG-R-Si-Au-NPs. Nanoparticles injected into the mice intravenously via the tail vein accumulated in the liver, whereas those injected intrarectally did not, indicating that they remain in the colon and do not pass through the colon wall into the systemic circulation.

A Scanning Transmission Electron Microscopy (STEM) Approach to Analyzing Large Volumes of Tissue to Detect Nanoparticles

PubMed Central

Kempen, Paul J.; Thakor, Avnesh S.; Zavaleta, Cristina; Gambhir, Sanjiv S.; Sinclair, Robert

2013-01-01

The use of nanoparticles for the diagnosis and treatment of cancer requires the complete characterization of their toxicity, including accurately locating them within biological tissues. Owing to their size, traditional light microscopy techniques are unable to resolve them. Transmission electron microscopy provides the necessary spatial resolution to image individual nanoparticles in tissue but is severely limited by the very small analysis volume, usually on the order of tens of cubic microns. In this work we developed a scanning transmission electron microscopy (STEM) approach to analyze large volumes of tissue for the presence of polyethylene glycol coated Raman-active-silica-gold-nanoparticles (PEG-R-Si-Au-NPs). This approach utilizes the simultaneous bright and dark field imaging capabilities of STEM along with careful control of the image contrast settings to readily identify PEG-R-Si-Au-NPs in mouse liver tissue without the need for additional time consuming analytical characterization. We utilized this technique to analyze 243,000 µm3 of mouse liver tissue for the presence of PEG-R-Si-Au-NPs. Nanoparticles injected into the mice intravenously via the tail-vein accumulated in the liver while those injected intrarectally did not, indicating that they remain in the colon and do not pass through the colon wall into the systemic circulation. PMID:23803218

Synthesis of Higher Alcohols via Syngas on Cu/Zn/Si Catalysts. Effect of Polyethylene Glycol Content

NASA Astrophysics Data System (ADS)

Cui, Rong-Ji; Yan, Xing; Fan, Jin-Chuan; Huang, Wei

2018-05-01

Cu/Zn/Si catalysts with different polyethylene glycol (PEG) content were prepared by a complete liquid-phase method, and characterized by XRD, H2-TPR, N2-adsorption, and XPS. The influence of PEG content on the higher alcohols synthesis from syngas was investigated. The results showed that addition of PEG can influence the texture and surface properties of the catalysts, and therefore affect their activity and product distribution. With an increase in PEG content, BET surface area, Cu crystallite size and surface active ingredient content of the catalysts first increased and then decreased, the CO conversion had similar variation tendency. However, the pore volume and pore diameter of the catalyst increased, and the binding energy of the active component and the content of Cu2O decreased, which resulted in higher catalyst selectivity towards higher alcohols. The highest C2+OH selectivity in total alcohols was 60.6 wt %.

Enhancing the Durability and Carrier Selectivity of Perovskite Solar Cells Using a Blend Interlayer.

PubMed

Sin, Dong Hun; Jo, Sae Byeok; Lee, Seung Goo; Ko, Hyomin; Kim, Min; Lee, Hansol; Cho, Kilwon

2017-05-31

A mechanically and thermally stable and electron-selective ZnO/CH 3 NH 3 PbI 3 interface is created via hybridization of a polar insulating polymer, poly(ethylene glycol) (PEG), into ZnO nanoparticles (NPs). PEG successfully passivates the oxygen defects on ZnO and prevents direct contact between CH 3 NH 3 PbI 3 and defects on ZnO. A uniform CH 3 NH 3 PbI 3 film is formed on a soft ZnO:PEG layer after dispersion of the residual stress from the volume expansion during CH 3 NH 3 PbI 3 conversion. PEG also increases the work of adhesion of the CH 3 NH 3 PbI 3 film on the ZnO:PEG layer and holds the CH 3 NH 3 PbI 3 film with hydrogen bonding. Furthermore, PEG tailors the interfacial electronic structure of ZnO, reducing the electron affinity of ZnO. As a result, a selective electron-collection cathode is formed with a reduced electron affinity and a deep-lying valence band of ZnO, which significantly enhances the carrier lifetime (473 μs) and photovoltaic performance (15.5%). The mechanically and electrically durable ZnO:PEG/CH 3 NH 3 PbI 3 interface maintains the sustainable performance of the solar cells over 1 year. A soft and durable cathodic interface via PEG hybridization in a ZnO layer is an effective strategy toward flexible electronics and commercialization of the perovskite solar cells.

In Vivo Anticancer Efficacy and Toxicity Studies of a Novel Polymer Conjugate N-Acetyl Glucosamine (NAG)-PEG-Doxorubicin for Targeted Cancer Therapy.

PubMed

Pawar, Smita; Mahajan, Ketan; Vavia, Pradeep

2017-11-01

A novel polymer-drug conjugate, polyethylene glycol-N-(acetyl)-glucosamine-doxorubicin (PEG-NAG-DOX) was evaluated in this study for its in vivo potential for treatment of tumours demonstrating improved efficacy and reduced toxicity. The proposed polymer-drug conjugate comprised of polyethylene glycol-maleimide (mPEG-MAL, 30000 Da) as a carrier, doxorubicin (DOX) as an anticancer drug and N-acetyl glucosamine (NAG) as a targeting moiety as well as penetration enhancer. Doxorubicin has a potent and promising anticancer activity; however, severe cardiotoxicity limits its application in cancer treatment. By modifying DOX in PEG-NAG-DOX prodrug conjugate, we aimed to eliminate this limitation. In vivo anticancer efficacy of the conjugate was evaluated using BDF mice-induced skin melanoma model by i.v. administration of DOX conjugates. Anticancer efficacy studies were done by comparing tumour volume, body weight, organ index and percent survival rate of the animals. Tumour suppression achieved by PEG-NAG-DOX at the cumulative dose of 7.5 mg/kg was two-fold better than that achieved by DOX solution. Also, the survival rate for PEG-NAG-DOX conjugate was >70% as compared to <50% survival rate for DOX solution. In addition, toxicity studies and histopathological studies revealed that while maintaining its cytotoxicity towards tumour cells, PEG-NAG-DOX conjugate showed no toxicities to major organs. Therefore, PEG-NAG-DOX conjugate can be suggested as a desirable candidate for targeted cancer therapy.

Brazilian Propolis: A Natural Product That Improved the Fungicidal Activity by Blood Phagocytes

PubMed Central

Possamai, Muryllo Mendes; Honorio-França, Adenilda Cristina; Reinaque, Ana Paula Barcelos; França, Eduardo Luzia; Souto, Paula Cristina de Souza

2013-01-01

Natural product incorporation into microcarriers increases the bioavailability of these compounds, consequently improving their therapeutic properties. Natural products, particularly those from bees such as propolis, are widely used in popular medicine. Propolis is a powerful treatment for several diseases. In this context, the present study evaluated the effect of propolis Scaptotrigona sp. and its fractions, alone or adsorbed to polyethylene glycol (PEG) microspheres, on the activity of human phagocytes against Candida albicans. The results show that propolis exerts a stimulatory effect on these cells to assist in combating the fungus, especially as the crude extract is compared with the fractions. However, when incorporated into microspheres, these properties were significantly potentiated. These results suggest that propolis adsorbed onto PEG microspheres has immunostimulatory effects on phagocytes in human blood. Therefore, propolis may potentially be an additional natural product that can be used for a variety of therapies. PMID:23509737

Bromelain purification through unconventional aqueous two-phase system (PEG/ammonium sulphate).

PubMed

Coelho, D F; Silveira, E; Pessoa Junior, A; Tambourgi, E B

2013-02-01

This paper focuses on the feasibility of unconventional aqueous two-phase systems for bromelain purification from pineapple processing waste. The main difference in comparison with conventional systems is the integration of the liquid-liquid extraction technique with fractional precipitation, which can decrease the protein content with no loss of biological activity by removing of unwanted molecules. The analysis of the results was based on the response surface methodology and revealed that the use of the desirability optimisation methodology (DOM) was necessary to achieve higher purification factor values and greater bromelain recovery. The use of DOM yielded an 11.80-fold purification factor and 66.38 % biological activity recovery using poly(ethylene glycol) (PEG) with a molar mass of 4,000, 10.86 % PEG concentration (m/m) and 36.21 % saturation of ammonium sulphate.

Split-dose administration of a dual-action, low-volume bowel cleanser for colonoscopy: the SEE CLEAR I study.

PubMed

Rex, Douglas K; Katz, Philip O; Bertiger, Gerald; Vanner, Stephen; Hookey, Lawrence C; Alderfer, Vivian; Joseph, Raymond E

2013-07-01

New bowel cleansers for colonoscopy that lead to improved efficacy, safety, and tolerability are needed. This study evaluated a nonphosphate, dual-action, low-volume, orange-flavored preparation containing sodium picosulfate and magnesium citrate (P/MC). Multicenter, assessor-blinded, randomized, noninferiority study. University hospitals, academic medical centers, and private clinics across the United States. Adults preparing for colonoscopy. P/MC versus 2 L of polyethylene glycol solution (2L PEG-3350) and two 5-mg bisacodyl tablets. This phase 3 study investigated the efficacy, safety, and tolerability of split-dose administration of P/MC versus day-before dosing of 2L PEG-3350 and two 5-mg bisacodyl tablets (SEE CLEAR I study). Efficacy was evaluated by using the Aronchick and Ottawa scales; noninferiority and superiority analyses were performed. Safety was assessed by monitoring adverse events (AEs). Tolerability was measured via a patient questionnaire. The intent-to-treat population consisted of 601 patients who self-administered P/MC (n = 304) or 2L PEG-3350 and bisacodyl tablets (n = 297). P/MC was superior to 2L PEG-3350 and bisacodyl tablets in overall colon cleansing (84.2% vs 74.4%; 1-sided 97.5% confidence interval [CI], 3.4) (Aronchick scores of excellent or good) and in cleansing of the ascending (89.5% vs 78.8%; 1-sided 97.5% CI, 4.9), mid (transverse and descending) (92.4% vs 85.9%; 1-sided 97.5% CI, 1.6), and rectosigmoid (92.4% vs 87.2%; 1-sided 97.5% CI, 0.4) segments of the colon (Ottawa scores of excellent, good, or fair). Commonly reported AEs related to the bowel preparations were nausea, vomiting, headache, and chills. Patient-reported tolerability, including ease of consumption and taste, was significantly higher for P/MC than 2L PEG-3350 and bisacodyl tablets (P < .0001). Because of differences in administration and volume of the bowel preparations, the study was designed to be a single-assessor, blinded study. The bowel-cleansing effects and patient acceptability of split-dose P/MC were superior to day-before dosing with 2L PEG-3350 and bisacodyl tablets. Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Purification of inclusion bodies using PEG precipitation under denaturing conditions to produce recombinant therapeutic proteins from Escherichia coli.

PubMed

Chen, Huanhuan; Li, Ninghuan; Xie, Yueqing; Jiang, Hua; Yang, Xiaoyi; Cagliero, Cedric; Shi, Siwei; Zhu, Chencen; Luo, Han; Chen, Junsheng; Zhang, Lei; Zhao, Menglin; Feng, Lei; Lu, Huili; Zhu, Jianwei

2017-07-01

It has been documented that the purification of inclusion bodies from Escherichia coli by size exclusion chromatography (SEC) may benefit subsequent refolding and recovery of recombinant proteins. However, loading volume and the high cost of the column limits its application in large-scale manufacturing of biopharmaceutical proteins. We report a novel process using polyethylene glycol (PEG) precipitation under denaturing conditions to replace SEC for rapid purification of inclusion bodies containing recombinant therapeutic proteins. Using recombinant human interleukin 15 (rhIL-15) as an example, inclusion bodies of rhIL-15 were solubilized in 7 M guanidine hydrochloride, and rhIL-15 was precipitated by the addition of PEG 6000. A final concentration of 5% (w/v) PEG 6000 was found to be optimal to precipitate target proteins and enhance recovery and purity. Compared to the previously reported S-200 size exclusion purification method, PEG precipitation was easier to scale up and achieved the same protein yields and quality of the product. PEG precipitation also reduced manufacturing time by about 50 and 95% of material costs. After refolding and further purification, the rhIL-15 product was highly pure and demonstrated a comparable bioactivity with a rhIL-15 reference standard. Our studies demonstrated that PEG precipitation of inclusion bodies under denaturing conditions holds significant potential as a manufacturing process for biopharmaceuticals from E. coli protein expression systems.

Reduced Cathartic Bowel Preparation for CT Colonography: Prospective Comparison of 2-L Polyethylene Glycol and Magnesium Citrate

PubMed Central

Keedy, Alexander W.; Aslam, Rizwan; Weinstein, Stefanie; Landeras, Luis A.; Shah, Janak N.; McQuaid, Kenneth R.; Yeh, Benjamin M.

2011-01-01

Purpose: To prospectively compare adequacy of colonic cleansing, adequacy of solid stool and fluid tagging, and patient acceptance by using reduced-volume, 2-L polyethylene glycol (PEG) versus magnesium citrate bowel preparations for CT colonography. Materials and Methods: This study was approved by the institutional Committee on Human Research and was compliant with HIPAA; all patients provided written consent. In this randomized, investigator-blinded study, 50 patients underwent oral preparation with either a 2-L PEG or a magnesium citrate solution, tagging with oral contrast agents, and subsequent CT colonography and segmentally unblinded colonoscopy. The residual stool (score 0 [best] to 3 [worst]) and fluid (score 0 [best] to 4 [worst]) burden and tagging adequacy were qualitatively assessed. Residual fluid attenuation was recorded as a quantitative measure of tagging adequacy. Patients completed a tolerance questionnaire within 2 weeks of scanning. Preparations were compared for residual stool and fluid by using generalized estimating equations; the Mann-Whitney test was used to compare the qualitative tagging score, mean residual fluid attenuation, and adverse effects assessed on the patient experience questionnaire. Results: The mean residual stool (0.90 of three) and fluid burden (1.05 of four) scores for PEG were similar to those for magnesium citrate (0.96 [P = .58] and 0.98 [P = .48], respectively). However, the mean fecal and fluid tagging scores were significantly better for PEG (0.48 and 0.28, respectively) than for magnesium citrate (1.52 [P < .01] and 1.28 [P < .01], respectively). Mean residual fluid attenuation was higher for PEG (765 HU) than for magnesium citrate (443 HU, P = .01), and mean interpretation time was shorter for PEG (14.8 minutes) than for magnesium citrate (18.0 minutes, P = .04). Tolerance ratings were not significantly different between preparations. Conclusion: Reduced-volume PEG and magnesium citrate bowel preparations demonstrated adequate cleansing effectiveness for CT colonography, with better tagging and shorter interpretation time observed in the PEG group. Adequate polyp detection was maintained but requires further validation because of the small number of clinically important polyps. © RSNA, 2011 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11110217/-/DC1 PMID:21873253

[Cerebral water and electrolytes during changes in the osmolarity and volume of the extracellular fluid].

PubMed

Pinegin, L E; Tibekina, L M; Shakhmatova, E I; Natochin, Iu

1979-01-01

The increase of osmolarity in the blood serum after administration of polyethylenglycol-400 (PEG) as well as the sharp increase of the renal loss of fluid under the influence of furosemide insignificantly affected the water contents in the white and grey brain substance. A slight dehydration of the grey substance occured on combination of osmotic gradient effect and the renal loss of fluid. Preservation of initial hydration of the brain within the skull on administration of PEG and furosemide is due to redistribution of the fluid phases: dehydration of cells is followed by an increase in the volume of sodium-containing tissue fluid where upon the amount of sodium and calcium in the tissue practically does not change.

Continuous versus bolus tube feeds: Does the modality affect glycemic variability, tube feeding volume, caloric intake, or insulin utilization?

PubMed

Evans, David C; Forbes, Rachel; Jones, Christian; Cotterman, Robert; Njoku, Chinedu; Thongrong, Cattleya; Tulman, David; Bergese, Sergio D; Thomas, Sheela; Papadimos, Thomas J; Stawicki, Stanislaw P

2016-01-01

Enteral nutrition (EN) is very important to optimizing outcomes in critical illness. Debate exists regarding the best strategy for enteral tube feeding (TF), with concerns that bolus TF (BTF) may increase glycemic variability (GV) but result in fewer nutritional interruptions than continuous TF (CTF). This study examines if there is a difference in GV, insulin usage, TF volume, and caloric delivery among intensive care patients receiving BTF versus CTF. We hypothesize that there are no significant differences between CTF and BTF when comparing the above parameters. Prospective, randomized pilot study of critically ill adult patients undergoing percutaneous endoscopic gastrostomy (PEG) placement for EN was performed between March 1, 2012 and May 15, 2014. Patients were randomized to BTF or CTF. Glucose values, insulin use, TF volume, and calories administered were recorded. Data were organized into 12-h epochs for statistical analyses and GV determination. In addition, time to ≥80% nutritional delivery goal, demographics, Acute Physiology and Chronic Health Evaluation II scores, and TF interruptions were examined. When performing BTF versus CTF assessments, continuous parameters were compared using Mann-Whitney U-test or repeated measures t-test, as appropriate. Categorical data were analyzed using Fisher's exact test. No significant demographic or physiologic differences between the CTF (n = 24) and BTF (n = 26) groups were seen. The immediate post-PEG 12-h epoch showed significantly lower GV and median TF volume for patients in the CTF group. All subsequent epochs (up to 18 days post-PEG) showed no differences in GV, insulin use, TF volume, or caloric intake. Insulin use for both groups increased when comparing the first 24 h post-PEG values to measurements from day 8. There were no differences in TF interruptions, time to ≥80% nutritional delivery goal, or hypoglycemic episodes. This study demonstrated no clinically relevant differences in GV, insulin use, TF volume or caloric intake between BTF and CTF groups. Despite some shortcomings, our data suggest that providers should not feel limited to BTF or CTF because of concerns for GV, time to goal nutrition, insulin use, or caloric intake, and should consider other factors such as resource utilization, ease of administration, and/or institutional/patient characteristics.

Improving of bowel cleansing effect for polyethylene glycol with ascorbic acid using simethicone

PubMed Central

Yoo, In Kyung; Jeen, Yoon Tae; Kang, Seung Hun; Lee, Jae Hyung; Kim, Seung Han; Lee, Jae Min; Choi, Hyuk Soon; Kim, Eun Sun; Keum, Bora; Chun, Hoon Jai; Lee, Hong Sik; Kim, Chang Duck

2016-01-01

Abstract Background and Aim: Low-volume polyethylene glycol with ascorbic acid (PEG-Asc) use is reported to be as safe and effective as traditional 4-L polyethylene glycol use. However, PEG-Asc produces bubbles, which cause problems during colonoscopy. Data on the effects of using antifoaming agents such as simethicone with PEG-Asc are lacking. The aim of this CONSORT-prospective, randomized, observer-blinded, controlled trial is to compare the quality of bowel preparation and compliance between PEG-Asc users and PEG-Asc plus simethicone users. Methods: Adult outpatients aged 18 to 80 years undergoing colonoscopy were recruited to the study. Two hundred sixty patients were randomly assigned to 1 of 2 treatment arms, PEG-Asc or PEG-Asc plus simethicone. The primary outcome measure was the bowel cleansing quality using Boston bowel preparation scale and bubble scores. The secondary outcome measures were patient tolerability and doctor tolerability. Results: The simethicone group showed superior cleansing results (6–9 Boston scale scores: 99% vs. 84%, <5% bubble scores: 96% vs. 49%, P < 0.001) and fewer gastrointestinal symptoms (abdominal fullness: 24% vs. 55%, colicky pain: 5% vs. 24%, P < 0.001) than the non-simethicone group. Moreover, endoscopist fatigue during colonoscopy was lower in the simethicone group than in the non-simethicone group (1.31 ± 0.75 vs. 2.97 ± 2.14, P < 0.001). Conclusion: PEG-Asc plus simethicone use was more effective and associated with better patient and endoscopist tolerance than PEG-Asc use. Therefore, this combination is recommended as one of the promising methods for bowel preparation before colonoscopy. PMID:27428209

Improving of bowel cleansing effect for polyethylene glycol with ascorbic acid using simethicone: A randomized controlled trial.

PubMed

Yoo, In Kyung; Jeen, Yoon Tae; Kang, Seung Hun; Lee, Jae Hyung; Kim, Seung Han; Lee, Jae Min; Choi, Hyuk Soon; Kim, Eun Sun; Keum, Bora; Chun, Hoon Jai; Lee, Hong Sik; Kim, Chang Duck

2016-07-01

Low-volume polyethylene glycol with ascorbic acid (PEG-Asc) use is reported to be as safe and effective as traditional 4-L polyethylene glycol use. However, PEG-Asc produces bubbles, which cause problems during colonoscopy. Data on the effects of using antifoaming agents such as simethicone with PEG-Asc are lacking. The aim of this CONSORT-prospective, randomized, observer-blinded, controlled trial is to compare the quality of bowel preparation and compliance between PEG-Asc users and PEG-Asc plus simethicone users. Adult outpatients aged 18 to 80 years undergoing colonoscopy were recruited to the study. Two hundred sixty patients were randomly assigned to 1 of 2 treatment arms, PEG-Asc or PEG-Asc plus simethicone. The primary outcome measure was the bowel cleansing quality using Boston bowel preparation scale and bubble scores. The secondary outcome measures were patient tolerability and doctor tolerability. The simethicone group showed superior cleansing results (6-9 Boston scale scores: 99% vs. 84%, <5% bubble scores: 96% vs. 49%, P < 0.001) and fewer gastrointestinal symptoms (abdominal fullness: 24% vs. 55%, colicky pain: 5% vs. 24%, P < 0.001) than the non-simethicone group. Moreover, endoscopist fatigue during colonoscopy was lower in the simethicone group than in the non-simethicone group (1.31 ± 0.75 vs. 2.97 ± 2.14, P < 0.001). PEG-Asc plus simethicone use was more effective and associated with better patient and endoscopist tolerance than PEG-Asc use. Therefore, this combination is recommended as one of the promising methods for bowel preparation before colonoscopy.

Enhancement of radiosensitivity of melanoma cells by pegylated gold nanoparticles under irradiation of megavoltage electrons.

PubMed

Mousavi, Mehdi; Nedaei, Hassan Ali; Khoei, Samideh; Eynali, Samira; Khoshgard, Karim; Robatjazi, Mostafa; Iraji Rad, Rasoul

2017-02-01

Gold nanoparticles (GNP) have significant potential as radiosensitizer agents due to their distinctive properties. Several studies have shown that the surface modification of nanoparticles with methyl polyethylene glycol (mPEG) can increase their biocompatibility. However, the present study investigated the radiosensitization effects of mPEG-coated GNP (mPEG-GNP) in B16F10 murine melanoma cells under irradiation of 6 MeV Electron beam. The synthesized GNP were characterized by UV-Visible spectroscopy, dynamic light scattering, transmission electron microscopy, and zeta potential. Enhancement of radiosensitization was evaluated by the clonogenic assay at different radiation doses of megavoltage electron beams. It was observed that mPEG-GNP with a hydrodynamic size of approximately 50 nm are almost spherical and cellular uptake occurred at all concentrations. Both proliferation efficiency and survival fraction decreased with increasing mPEG-GNP concentration. Furthermore, significant GNP sensitization occurred with a maximum dose enhancement factor of 1.22 at a concentration of 30 μM. Pegylated-GNP are taken up by B16F10 cancer cells and cause radiosensitization in the presence of 6 MeV electrons. The radiosensitization effects of GNP may probably be due to biological processes. Therefore, the underlying biological mechanisms beyond the physical dose enhancement need to be further clarified.

Preparation and in vitro characterization of 9-nitrocamptothecin-loaded long circulating nanoparticles for delivery in cancer patients.

PubMed

Derakhshandeh, Katayoun; Soheili, Marzieh; Dadashzadeh, Simin; Saghiri, Reza

2010-08-09

The purpose in this study was to investigate poly(ethylene glycol)-modified poly (d,l-lactide-co-glycolide) nanoparticles (PLGA-PEG-NPs) loading 9-nitrocamptothecin (9-NC) as a potent anticancer drug. 9-NC is an analog of the natural plant alkaloid camptothecin that has shown high antitumor activity and is currently in the end stage of clinical trial. Unfortunately, at physiological pH, these potent agents undergo a rapid and reversible hydrolysis with the loss of antitumor activity. Previous researchers have shown that the encapsulation of this drug in PLGA nanoparticles could increase its stability and release profile. In this research we investigated PLGA-PEG nanoparticles and their effect on in vitro characteristics of this labile drug. 9-NC-PLGA-PEG nanoparticles with particle size within the range of 148.5 ± 30 nm were prepared by a nanoprecipitation method. The influence of four different independent variables (amount of polymer, percent of emulsifier, internal phase volume, and external phase volume) on nanoparticle drug-loading was studied. Differential scanning calorimetry and X-ray diffractometry were also evaluated for physical characterizing. The results of optimized formulation showed a narrow size distribution, suitable zeta potential (+1.84), and a drug loading of more than 45%. The in vitro drug release from PLGA-PEG NPs showed a sustained release pattern of up to 120 hours and comparing with PLGA-NPs had a significant decrease in initial burst effect. These experimental results indicate that PLGA-PEG-NPs (versus PLGA-NPs) have a better physicochemical characterization and can be developed as a drug carrier in order to treat different malignancies.

Preparation and in vitro characterization of 9-nitrocamptothecin-loaded long circulating nanoparticles for delivery in cancer patients

PubMed Central

Derakhshandeh, Katayoun; Soheili, Marzieh; Dadashzadeh, Simin; Saghiri, Reza

2010-01-01

The purpose in this study was to investigate poly(ethylene glycol)-modified poly (d,l-lactide-co-glycolide) nanoparticles (PLGA-PEG-NPs) loading 9-nitrocamptothecin (9-NC) as a potent anticancer drug. 9-NC is an analog of the natural plant alkaloid camptothecin that has shown high antitumor activity and is currently in the end stage of clinical trial. Unfortunately, at physiological pH, these potent agents undergo a rapid and reversible hydrolysis with the loss of antitumor activity. Previous researchers have shown that the encapsulation of this drug in PLGA nanoparticles could increase its stability and release profile. In this research we investigated PLGA-PEG nanoparticles and their effect on in vitro characteristics of this labile drug. 9-NC-PLGA-PEG nanoparticles with particle size within the range of 148.5 ± 30 nm were prepared by a nanoprecipitation method. The influence of four different independent variables (amount of polymer, percent of emulsifier, internal phase volume, and external phase volume) on nanoparticle drug-loading was studied. Differential scanning calorimetry and X-ray diffractometry were also evaluated for physical characterizing. The results of optimized formulation showed a narrow size distribution, suitable zeta potential (+1.84), and a drug loading of more than 45%. The in vitro drug release from PLGA-PEG NPs showed a sustained release pattern of up to 120 hours and comparing with PLGA-NPs had a significant decrease in initial burst effect. These experimental results indicate that PLGA-PEG-NPs (versus PLGA-NPs) have a better physicochemical characterization and can be developed as a drug carrier in order to treat different malignancies. PMID:20957168

Assessment of canine vocal fold function after injection of a new biomaterial designed to treat phonatory mucosal scarring.

PubMed

Karajanagi, Sandeep S; Lopez-Guerra, Gerardo; Park, Hyoungshin; Kobler, James B; Galindo, Marilyn; Aanestad, Jon; Mehta, Daryush D; Kumai, Yoshihiko; Giordano, Nicholas; d'Almeida, Anthony; Heaton, James T; Langer, Robert; Herrera, Victoria L M; Faquin, William; Hillman, Robert E; Zeitels, Steven M

2011-03-01

Most cases of irresolvable hoarseness are due to deficiencies in the pliability and volume of the superficial lamina propria of the phonatory mucosa. By using a US Food and Drug Administration-approved polymer, polyethylene glycol (PEG), we created a novel hydrogel (PEG30) and investigated its effects on multiple vocal fold structural and functional parameters. We injected PEG30 unilaterally into 16 normal canine vocal folds with survival times of 1 to 4 months. High-speed videos of vocal fold vibration, induced by intratracheal airflow, and phonation threshold pressures were recorded at 4 time points per subject. Three-dimensional reconstruction analysis of 11.7 T magnetic resonance images and histologic analysis identified 3 cases wherein PEG30 injections were the most superficial, so as to maximally impact vibratory function. These cases were subjected to in-depth analyses. High-speed video analysis of the 3 selected cases showed minimal to no reduction in the maximum vibratory amplitudes of vocal folds injected with PEG30 compared to the non-injected, contralateral vocal fold. All PEG30-injected vocal folds displayed mucosal wave activity with low average phonation threshold pressures. No significant inflammation was observed on microlaryngoscopic examination. Magnetic resonance imaging and histologic analyses revealed time-dependent resorption of the PEG30 hydrogel by phagocytosis with minimal tissue reaction or fibrosis. The PEG30 hydrogel is a promising biocompatible candidate biomaterial to restore form and function to deficient phonatory mucosa, while not mechanically impeding residual endogenous superficial lamina propria.

Enhanced detection of infectious hematopoietic necrosis virus by pretreatment of cell monolayers with polyethylene glycol

USGS Publications Warehouse

Batts, W.N.; Winton, J.R.

1989-01-01

To improve quantification of very low levels of infectious hematopoietic necrosis virus (IHNV) in samples of tissue, ovarian fluid, or natural water supplies, we tested the ability of polyethylene glycol (PEG) to enhance the sensitivity and speed of the plaque assay system. We compared 4, 7, and 10% solutions of PEG of molecular weight 6,000, 8,000, or 20,000 applied at selected volumes and for various durations. When cell monolayers of epithelioma papulosum cyprini (EPC), fathead minnow (FHM), chinook salmon embryo (CHSE-214), and bluegill fry (BF2) were pretreated with 7% PEG-20,000, they produced 4-17-fold increases in plaque assay titers of IHNV. The plaque assay titers of viral hemorrhagic septicemia virus, chum salmon reovirus, and chinook salmon paramyxovirus were also enhanced by exposure of CHSE-214 cells to PEG, but the titers of infectious pancreatic necrosis virus and Oncorhynchus masou virus were not substantially changed. Plaques formed by IHNV on PEG-treated EPC cells incubated at 15°C had a larger mean diameter at 6 d than those on control cells at 8 d; this suggests the assay could be shortened by use of PEG. Pretreatment of EPC cell monolayers with PEG enabled detection of IHNV in some samples that appeared negative with untreated cells. For example, when ovarian fluid samples from chinook salmon Oncorhynchus tshawytscha were inoculated onto untreated monolayers of EPC cells, IHNV was detected in only 11 of 51 samples; 17 of the samples were positive when PEG-treated EPC cells were used.PDF

A Bayesian Approach for Population Pharmacokinetic Modeling of Pegylated Interferon α-2a in Hepatitis C Patients.

PubMed

Saleh, Mohammad I

2017-11-01

Pegylated interferon α-2a (PEG-IFN-α-2a) is an antiviral drug used for the treatment of chronic hepatitis C virus (HCV) infection. This study describes the population pharmacokinetics of PEG-IFN-α-2a in hepatitis C patients using a Bayesian approach. A possible association between patient characteristics and pharmacokinetic parameters is also explored. A Bayesian population pharmacokinetic modeling approach, using WinBUGS version 1.4.3, was applied to a cohort of patients (n = 292) with chronic HCV infection. Data were obtained from two phase III studies sponsored by Hoffmann-La Roche. Demographic and clinical information were evaluated as possible predictors of pharmacokinetic parameters during model development. A one-compartment model with an additive error best fitted the data, and a total of 2271 PEG-IFN-α-2a measurements from 292 subjects were analyzed using the proposed population pharmacokinetic model. Sex was identified as a predictor of PEG-IFN-α-2a clearance, and hemoglobin baseline level was identified as a predictor of PEG-IFN-α-2a volume of distribution. A population pharmacokinetic model of PEG-IFN-α-2a in patients with chronic HCV infection was presented in this study. The proposed model can be used to optimize PEG-IFN-α-2a dosing in patients with chronic HCV infection. Optimal PEG-IFN-α-2a selection is important to maximize response and/or to avoid potential side effects such as thrombocytopenia and neutropenia. NV15942 and NV15801.

Lamellar biogels comprising fluid membranes with a newly synthesized class of polyethylene glycol-surfactants

NASA Astrophysics Data System (ADS)

Warriner, Heidi E.; Davidson, Patrick; Slack, Nelle L.; Schellhorn, Matthias; Eiselt, Petra; Idziak, Stefan H. J.; Schmidt, Hans-Werner; Safinya, Cyrus R.

1997-09-01

A series of four polymer-surfactant macromolecules, each consisting of a double-chain hydrophobic moiety attached onto a monofunctional polyethylene glycol (PEG) polymer chain, were synthesized in order to study their effect upon the fluid lamellar liquid crystalline (Lα) phase of the dimyristoylphosphatidylcholine/pentanol/water system. The main finding of this study is that the addition of these compounds induces a new lamellar gel, called Lα,g. We have determined the phase diagrams as a function of PEG-surfactant concentration, cPEG, and weight fraction water, ΦW. All phase diagrams are qualitatively similar and show the existence of the gel. Unlike more common polymer physical gels, this gel can be induced either by increasing cPEG or by adding water at constant cPEG. In particular, less polymer is required for gelation as water concentration increases. Moreover, the gel phase is attained at concentrations of PEG-surfactant far below that required for classical polymer gels and is stable at temperatures comparable to the lower critical solution temperature of free PEG-water mixtures. Small angle x-ray experiments demonstrate the lamellar structure of the gel phase, while wide angle x-ray scattering experiments prove that the structure is Lα, not Lβ' (a common chain-ordered phase which is also a gel). The rheological behavior of the Lα,g phase demonstrates the existence of three dimensional elastic properties. Polarized light microscopy of Lα,g samples reveals that the Lα,g is induced by a proliferation of defect structures, including whispy lines, spherulitic defects, and a nematiclike Schlieren texture. We propose a model of topological defects created by the aggregation of PEG-surfactant into highly curved regions within the membranes. This model accounts for both the inverse relationship between ΦW and cPEG observed along the gel transition line and the scaling dependence of the interlayer spacing at the gel transition with the PEG molecular weight. These Lα hydrogels could serve as the matrix for membrane-anchored peptides, proteins or other drug molecules, creating a "bioactive gel" with mechanical stability deriving from the polymer-lipid minority component.

Water-in-Water Emulsion Based Synthesis of Hydrogel Nanospheres with Tunable Release Kinetics

NASA Astrophysics Data System (ADS)

Aydın, Derya; Kızılel, Seda

2017-07-01

Poly(ethylene glycol) (PEG) micro/nanospheres have several unique advantages as polymer based drug delivery systems (DDS) such as tunable size, large surface area to volume ratio, and colloidal stability. Emulsification is one of the widely used methods for facile synthesis of micro/nanospheres. Two-phase aqueous system based on polymer-polymer immiscibility is a novel approach for preparation of water-in-water (w/w) emulsions. This method is promising for the synthesis of PEG micro/nanospheres for biological systems, since the emulsion is aqueous and do not require organic solvents or surfactants. Here, we report the synthesis of nano-scale PEG hydrogel particles using w/w emulsions using phase separation of dextran and PEG prepolymer. Dynamic light scattering (DLS) and scaning electron microscopy (SEM) results demonstrated that nano-scale hydrogel spheres could be obtained with this approach. We investigated the release kinetics of a model drug, pregabalin (PGB) from PEG nanospheres and demonstrated the influence of polymerization conditions on loading and release of the drug as well as the morphology and size distribution of PEG nanospheres. The experimental drug release data was fitted to a stretched exponential function which suggested high correlation with experimental results to predict half-time and drug release rates from the model equation. The biocompatibility of nanospheres on human dermal fibroblasts using cell-survival assay suggested that PEG nanospheres with altered concentrations are non-toxic, and can be considered for controlled drug/molecule delivery.

SS-mPEG chemical modification of recombinant phospholipase C for enhanced thermal stability and catalytic efficiency.

PubMed

Fang, Xian; Wang, Xueting; Li, Guiling; Zeng, Jun; Li, Jian; Liu, Jingwen

2018-05-01

PEGylation is one of the most promising and extensively studied strategies for improving the properties of proteins as well as enzymic physical and thermal stability. Phospholipase C, hydrolyzing the phospholipids offers tremendous applications in diverse fields. However, the poor thermal stability and higher cost of production have restricted its industrial application. This study focused on improving the stabilization of recombinant PLC by chemical modification with methoxypolyethylene glycol-Succinimidyl Succinate (SS-mPEG, MW 5000). PLC gene from isolate Bacillus cereus HSL3 was fused with SUMO, a novel small ubiquitin-related modifier expression vector and over expressed in Escherichia coli. The soluble fraction of SUMO-PLC reached 80% of the total recombinant protein. The enzyme exhibited maximum catalytic activity at 80 °C and was relatively thermostable at 40-70 °C. It showed extensive substrate specificity pattern and marked activity toward phosphatidylcholine, which made it a typical non-specific PLC for industrial purpose. SS-mPEG-PLC complex exhibited an enhanced thermal stability at 70-80 °C and the catalytic efficiency (K cat /K m ) had increased by 3.03 folds compared with free PLC. CD spectrum of SS-mPEG-PLC indicated a possible enzyme aggregation after chemical modification, which contributed to the higher thermostability of SS-mPEG-PLC. The increase of antiparallel β sheets in secondary structure also made it more stable than parallel β sheets. The presence of SS-mPEG chains on the enzyme molecule surface somewhat changed the binding rate of the substrates, leading to a significant improvement in catalytic efficiency. This study provided an insight into the addition of SS-mPEG for enhancing the industrial applications of phospholipase C at higher temperature. Copyright © 2018 Elsevier B.V. All rights reserved.

Oral PEG 15-20 protects the intestine against radiation : role of lipid rafts.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valuckaite, V.; Zaborina, O.; Long, J.

Intestinal injury following abdominal radiation therapy or accidental exposure remains a significant clinical problem that can result in varying degrees of mucosal destruction such as ulceration, vascular sclerosis, intestinal wall fibrosis, loss of barrier function, and even lethal gut-derived sepsis. We determined the ability of a high-molecular-weight polyethylene glycol-based copolymer, PEG 15-20, to protect the intestine against the early and late effects of radiation in mice and rats and to determine its mechanism of action by examining cultured rat intestinal epithelia. Rats were exposed to fractionated radiation in an established model of intestinal injury, whereby an intestinal segment is surgicallymore » placed into the scrotum and radiated daily. Radiation injury score was decreased in a dose-dependent manner in rats gavaged with 0.5 or 2.0 g/kg per day of PEG 15-20 (n = 9-13/group, P < 0.005). Complementary studies were performed in a novel mouse model of abdominal radiation followed by intestinal inoculation with Pseudomonas aeruginosa (P. aeruginosa), a common pathogen that causes lethal gut-derived sepsis following radiation. Mice mortality was decreased by 40% in mice drinking 1% PEG 15-20 (n = 10/group, P < 0.001). Parallel studies were performed in cultured rat intestinal epithelial cells treated with PEG 15-20 before radiation. Results demonstrated that PEG 15-20 prevented radiation-induced intestinal injury in rats, prevented apoptosis and lethal sepsis attributable to P. aeruginosa in mice, and protected cultured intestinal epithelial cells from apoptosis and microbial adherence and possible invasion. PEG 15-20 appeared to exert its protective effect via its binding to lipid rafts by preventing their coalescence, a hallmark feature in intestinal epithelial cells exposed to radiation.« less

Effect of Synthetic High Density Lipoproteins Modification with Polyethylene Glycol on Pharmacokinetics and Pharmacodynamics.

PubMed

Li, Dan; Fawaz, Maria V; Morin, Emily E; Ming, Ran; Sviridov, Denis; Tang, Jie; Ackermann, Rose; Olsen, Karl; Remaley, Alan T; Schwendeman, Anna

2018-01-02

Synthetic high density lipoprotein nanoparticles (sHDLs) capable of mobilizing excess cholesterol from atherosclerotic arteries and delivering it to the liver for elimination have been shown to reduce plaque burden in patients. Unfortunately, sHDLs have a narrow therapeutic index and relative to the endogenous HDL shorter circulation half-life. Surface modification with polyethylene glycol (PEG) was investigated for its potential to extend sHDL circulation in vivo. Various amounts (2.5, 5, and 10%) and different chain lengths (2 and 5 kDa) of PEG-modified lipids were incorporated in sHDL's lipid membrane. Incorporating PEG did not reduce the ability of sHDL to facilitate cholesterol efflux, nor did it inhibit cholesterol uptake by the liver cells. By either adding more PEG or using PEG of longer chain lengths, the circulation half-life was extended. Addition of PEG also increased the area under the curve for the phospholipid component of sHDL (p < 0.05), but not for the apolipoprotein A-I peptide component of sHDL, suggesting sHDL is remodeled by endogenous lipoproteins in vivo. The extended phospholipid circulation led to a higher mobilization of plasma free cholesterol, a biomarker for facilitation of reverse cholesterol transport. The area under the cholesterol mobilization increased about 2-4-fold (p < 0.05), with greater increases observed for longer PEG chains and higher molar percentages of incorporated PEGylated lipids. Mobilized cholesterol was associated primarily with the HDL fraction, led to a transient increase in VLDL cholesterol, and returned to baseline 24 h postdose. Overall, PEGylation of sHDL led to beneficial changes in sHDL particle pharmacokinetic and pharmacodynamic behaviors.

Microarray profiling of human white adipose tissue after exogenous leptin injection.

PubMed

Taleb, S; Van Haaften, R; Henegar, C; Hukshorn, C; Cancello, R; Pelloux, V; Hanczar, B; Viguerie, N; Langin, D; Evelo, C; Zucker, J; Clément, K; Saris, W H M

2006-03-01

Leptin is a secreted adipocyte hormone that plays a key role in the regulation of body weight homeostasis. The leptin effect on human white adipose tissue (WAT) is still debated. The aim of this study was to assess whether the administration of polyethylene glycol-leptin (PEG-OB) in a single supraphysiological dose has transcriptional effects on genes of WAT and to identify its target genes and functional pathways in WAT. Blood samples and WAT biopsies were obtained from 10 healthy nonobese men before treatment and 72 h after the PEG-OB injection, leading to an approximate 809-fold increase in circulating leptin. The WAT gene expression profile before and after the PEG-OB injection was compared using pangenomic microarrays. Functional gene annotations based on the gene ontology of the PEG-OB regulated genes were performed using both an 'in house' automated procedure and GenMAPP (Gene Microarray Pathway Profiler), designed for viewing and analyzing gene expression data in the context of biological pathways. Statistical analysis of microarray data revealed that PEG-OB had a major down-regulated effect on WAT gene expression, as we obtained 1,822 and 100 down- and up-regulated genes, respectively. Microarray data were validated using reverse transcription quantitative PCR. Functional gene annotations of PEG-OB regulated genes revealed that the functional class related to immunity and inflammation was among the most mobilized PEG-OB pathway in WAT. These genes are mainly expressed in the cell of the stroma vascular fraction in comparison with adipocytes. Our observations support the hypothesis that leptin could act on WAT, particularly on genes related to inflammation and immunity, which may suggest a novel leptin target pathway in human WAT.

Laser-induced thermal coagulation enhances skin uptake of topically applied compounds.

PubMed

Haak, C S; Hannibal, J; Paasch, U; Anderson, R R; Haedersdal, M

2017-08-01

Ablative fractional laser (AFL) generates microchannels in skin surrounded by a zone of thermally altered tissue, termed the coagulation zone (CZ). The thickness of CZ varies according to applied wavelength and laser settings. It is well-known that AFL channels facilitate uptake of topically applied compounds, but the importance of CZ is unknown. Franz Cells were used to investigate skin uptake and permeation of fluorescent labeled polyethylene glycols (PEGs) with mean molecular weights (MW) of 350, 1,000, and 5,000 Da. Microchannels with CZ thicknesses ranging from 0 to 80 μm were generated from micro-needles (0 μm, CZ-0), and AFL (10,600 nm) applied to -80°C deep frozen skin (20 μm, CZ-20) and skin equilibrated to room temperature (80 μm, CZ-80). Channels penetrated into similar mid-dermal skin depths of 600-700 μm, and number of channels per skin area was similar. At 4 hours incubation, skin uptake of PEGs into CZ and dermis was evaluated by fluorescence microscopy at specific skin depths of 150, 400, and 1,000 μm and the transcutaneous permeation was quantified by fluorescence of receptor fluids. Overall, the highest uptake of PEGs was reached through microchannels surrounded by CZ compared to channels with no CZ (CZ-20 and CZ-80>CZ-0).The thickness of CZ affected PEG distribution in skin. A thin CZ-20 favored significantly higher mean fluorescence intensities inside CZ areas compared to CZ-80 (PEG 350, 1,000, and 5,000; P < 0.001). In dermis, the uptake through CZ-20 channels was significantly higher than through CZ-80 and CZ-0 at all skin depths (PEG 350, 1,000 and 5,000, 150-1,000 μm; P < 0.001). Correspondingly, transcutaneous permeation of PEG 350 was highest in CZ-20 compared to CZ-80 and CZ-0 samples (P < 0.001). Permeation of larger molecules (PEG 1,000 and PEG 5,000) was generally low. Uptake of topical compounds is higher through microchannels surrounded by a CZ than without a CZ. Moreover, CZ thickness influences PEG distribution, with highest PEG uptake achieved from microchannels surrounded by a thin CZ. Lasers Surg. Med. 49:582-591, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Formulation of polylactide-co-glycolic acid nanospheres for encapsulation and sustained release of poly(ethylene imine)-poly(ethylene glycol) copolymers complexed to oligonucleotides

PubMed Central

Sirsi, Shashank R; Schray, Rebecca C; Wheatley, Margaret A; Lutz, Gordon J

2009-01-01

Antisense oligonucleotides (AOs) have been shown to induce dystrophin expression in muscles cells of patients with Duchenne Muscular Dystrophy (DMD) and in the mdx mouse, the murine model of DMD. However, ineffective delivery of AOs limits their therapeutic potential. Copolymers of cationic poly(ethylene imine) (PEI) and non-ionic poly(ethylene glycol) (PEG) form stable nanoparticles when complexed with AOs, but the positive surface charge on the resultant PEG-PEI-AO nanoparticles limits their biodistribution. We adapted a modified double emulsion procedure for encapsulating PEG-PEI-AO polyplexes into degradable polylactide-co-glycolic acid (PLGA) nanospheres. Formulation parameters were varied including PLGA molecular weight, ester end-capping, and sonication energy/volume. Our results showed successful encapsulation of PEG-PEI-AO within PLGA nanospheres with average diameters ranging from 215 to 240 nm. Encapsulation efficiency ranged from 60 to 100%, and zeta potential measurements confirmed shielding of the PEG-PEI-AO cationic charge. Kinetic measurements of 17 kDa PLGA showed a rapid burst release of about 20% of the PEG-PEI-AO, followed by sustained release of up to 65% over three weeks. To evaluate functionality, PEG-PEI-AO polyplexes were loaded into PLGA nanospheres using an AO that is known to induce dystrophin expression in dystrophic mdx mice. Intramuscular injections of this compound into mdx mice resulted in over 300 dystrophin-positive muscle fibers distributed throughout the muscle cross-sections, approximately 3.4 times greater than for injections of AO alone. We conclude that PLGA nanospheres are effective compounds for the sustained release of PEG-PEI-AO polyplexes in skeletal muscle and concomitant expression of dystrophin, and may have translational potential in treating DMD. PMID:19351396

Addition of Lubiprostone to polyethylene glycol(PEG) enhances the quality & efficacy of colonoscopy preparation: a randomized, double-blind, placebo controlled trial.

PubMed

Banerjee, Rupa; Chaudhari, Hrushikesh; Shah, Nirish; Saravanan, Arjunan; Tandan, Manu; Reddy, D Nageshwar

2016-10-13

Adequate bowel preparation is an essential prerequisite for complete mucosal visualization during colonoscopy. Polyethylene glycol (PEG) solutions are commonly used. However the large volume of the solution is often poorly tolerated. Addition of Lubiprostone (LB) could improve the adequacy of standard PEG preparation & reduce requirement. The aims to assess adequacy of PEG preparation with addition of single dose LB (24mcg) vs placebo and efficacy of reduced dose PEG + LB compared with full dose PEG + LB. Single center prospective double blind randomized controlled trial. Part I: 442 patients for colonoscopy randomized to receive placebo (GrA) or single dose of LB (GrB) prior to PEG preparation. Quality of bowel preparation graded 0-9 according to Boston Bowel Preparation Scale (BBPS). BBPS-9: excellent and BBPS 0-4: repeat procedure. Part II: 146 patients randomized to receive LB + 1.5 L PEG (GrC; 75) or LB + 1 L PEG (GrD; 71). BBPS score compared with GrB (2 L PEG). Part I: 442 patients (221 GrA & 221 Gr B). LB resulted in significant improvement in total BBPS (7.44 + 0.14 vs. 6.36 + 0.16, p < 0.0001). 66.5 % Gr B vs 38 % Gr A had excellent prep; 42.5 % GrB vs 24 % GrA had adequate prep. Repeat procedure needed 9.5 % Gr B vs 16.7 % Gr A (P < 0.01). Part II: No difference in BBPS scores with lower doses (Gr C&D) compared to standard (GrB) (Mean BBPS 7.44 + 0.14 GrA,7.30 + 0.25 GrC;7.25 + 0.26 GrD;p >0.05). Single dose LB prior to PEG significantly enhanced bowel preparation compared to PEG alone. There was no significant difference in quality of preparation with lower doses of PEG when combined with LB. The study protocol was approved by institutional review board and the trial was registered on March 22, 2011 with clinicaltrials.gov ( NCT01324284 ).

Certification and uncertainty evaluation of the certified reference materials of poly(ethylene glycol) for molecular mass fractions by using supercritical fluid chromatography.

PubMed

Takahashi, Kayori; Kishine, Kana; Matsuyama, Shigetomo; Saito, Takeshi; Kato, Haruhisa; Kinugasa, Shinichi

2008-07-01

Poly(ethylene glycol) (PEG) is a useful water-soluble polymer that has attracted considerable interest in medical and biological science applications as well as in polymer physics. Through the use of a well-calibrated evaporative light-scattering detector coupled with high performance supercritical fluid chromatography, we are able to determine exactly not only the average mass but also all of the molecular mass fractions of PEG samples needed for certified reference materials issued by the National Metrology Institute of Japan. In addition, experimental uncertainty was determined in accordance with the Guide to the expression of uncertainty in measurement (GUM). This reference material can be used to calibrate measuring instruments, to control measurement precision, and to confirm the validity of measurement methods when determining molecular mass distributions and average molecular masses. Especially, it is suitable for calibration against both masses and intensities for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Reaction-Mediated Desorption of Macromolecules: Novel Phenomenon Enabling Simultaneous Reaction and Separation.

PubMed

Isakari, Yu; Kishi, Yuhi; Yoshimoto, Noriko; Yamamoto, Shuichi; Podgornik, Aleš

2018-02-02

Combining chemical reaction with separation offers several advantages. In this work possibility to induce spontaneous desorption of adsorbed macromolecules, once being PEGylated, through adjustment of the reagent composition is investigated. Bovine serum albumin (BSA) and activated oligonucleotide, 9T, are used as the test molecules and 20 kDa linear activated PEG is used for their PEGylation. BSA solid-phase PEGylation is performed on Q Sepharose HP. Distribution coefficient of BSA and PEG-BSA as a function of NaCl is determined using linear gradient elution (LGE) experiments and Yamamoto model. According to the distribution coefficient the selectivity between BSA and PEG - BSA of around 15 is adjusted by using NaCl. Spontaneous desorption of PEG - BSA is detected with no presence of BSA. However, due to a rather low selectivity, also desorption of BSA occurred at high elution volume. A similar procedure is applied for activated 9T oligonucleotide, this time using monolithic CIM QA disk monolithic column for adsorption. Selectivity of over 2000 is obtained by proper adjustment of PEG reagent composition. High selectivity enables spontaneous desorption of PEG-9T without any desorption of activated 9T. Both experiments demonstrates that reaction-mediated desorption of macromolecules is possible when the reaction conditions are properly tuned. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polyethylene glycol rinse solution: An effective way to prevent ischemia-reperfusion injury

PubMed Central

Zaouali, Mohamed Amine; Bejaoui, Mohamed; Calvo, Maria; Folch-Puy, Emma; Pantazi, Eirini; Pasut, Gianfranco; Rimola, Antoni; Ben Abdennebi, Hassen; Adam, René; Roselló-Catafau, Joan

2014-01-01

AIM: To test whether a new rinse solution containing polyethylene glycol 35 (PEG-35) could prevent ischemia-reperfusion injury (IRI) in liver grafts. METHODS: Sprague-Dawley rat livers were stored in University of Wisconsin preservation solution and then washed with different rinse solutions (Ringer’s lactate solution and a new rinse solution enriched with PEG-35 at either 1 or 5 g/L) before ex vivo perfusion with Krebs-Heinseleit buffer solution. We assessed the following: liver injury (transaminase levels), mitochondrial damage (glutamate dehydrogenase activity), liver function (bile output and vascular resistance), oxidative stress (malondialdehyde), nitric oxide, liver autophagy (Beclin-1 and LCB3) and cytoskeleton integrity (filament and globular actin fraction); as well as levels of metalloproteinases (MMP2 and MMP9), adenosine monophosphate-activated protein kinase (AMPK), heat shock protein 70 (HSP70) and heme oxygenase 1 (HO-1). RESULTS: When we used the PEG-35 rinse solution, reduced hepatic injury and improved liver function were noted after reperfusion. The PEG-35 rinse solution prevented oxidative stress, mitochondrial damage, and liver autophagy. Further, it increased the expression of cytoprotective heat shock proteins such as HO-1 and HSP70, activated AMPK, and contributed to the restoration of cytoskeleton integrity after IRI. CONCLUSION: Using the rinse solution containing PEG-35 was effective for decreasing liver graft vulnerability to IRI. PMID:25473175

Engineering of blended nanoparticle platform for delivery of mitochondria-acting therapeutics

PubMed Central

Marrache, Sean; Dhar, Shanta

2012-01-01

Mitochondrial dysfunctions cause numerous human disorders. A platform technology based on biodegradable polymers for carrying bioactive molecules to the mitochondrial matrix could be of enormous potential benefit in treating mitochondrial diseases. Here we report a rationally designed mitochondria-targeted polymeric nanoparticle (NP) system and its optimization for efficient delivery of various mitochondria-acting therapeutics by blending a targeted poly(d,l-lactic-co-glycolic acid)-block (PLGA-b)-poly(ethylene glycol) (PEG)-triphenylphosphonium (TPP) polymer (PLGA-b-PEG-TPP) with either nontargeted PLGA-b-PEG-OH or PLGA-COOH. An optimized formulation was identified through in vitro screening of a library of charge- and size-varied NPs, and mitochondrial uptake was studied by qualitative and quantitative investigations of cytosolic and mitochondrial fractions of cells treated with blended NPs composed of PLGA-b-PEG-TPP and a triblock copolymer containing a fluorescent quantum dot, PLGA-b-PEG-QD. The versatility of this platform was demonstrated by studying various mitochondria-acting therapeutics for different applications, including the mitochondria-targeting chemotherapeutics lonidamine and α-tocopheryl succinate for cancer, the mitochondrial antioxidant curcumin for Alzheimer’s disease, and the mitochondrial uncoupler 2,4-dinitrophenol for obesity. These biomolecules were loaded into blended NPs with high loading efficiencies. Considering efficacy, the targeted PLGA-b-PEG-TPP NP provides a remarkable improvement in the drug therapeutic index for cancer, Alzheimer’s disease, and obesity compared with the nontargeted construct or the therapeutics in their free form. This work represents the potential of a single, programmable NP platform for the diagnosis and targeted delivery of therapeutics for mitochondrial dysfunction-related diseases. PMID:22991470

Design, physicochemical characterization, and optimization of organic solution advanced spray-dried inhalable dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine poly(ethylene glycol) (DPPE-PEG) microparticles and nanoparticles for targeted respiratory nanomedicine delivery as dry powder inhalation aerosols

PubMed Central

Meenach, Samantha A; Vogt, Frederick G; Anderson, Kimberly W; Hilt, J Zach; McGarry, Ronald C; Mansour, Heidi M

2013-01-01

Novel advanced spray-dried and co-spray-dried inhalable lung surfactant-mimic phospholipid and poly(ethylene glycol) (PEG)ylated lipopolymers as microparticulate/nanoparticulate dry powders of biodegradable biocompatible lipopolymers were rationally formulated via an organic solution advanced spray-drying process in closed mode using various phospholipid formulations and rationally chosen spray-drying pump rates. Ratios of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine PEG (DPPE-PEG) with varying PEG lengths were mixed in a dilute methanol solution. Scanning electron microscopy images showed the smooth, spherical particle morphology of the inhalable particles. The size of the particles was statistically analyzed using the scanning electron micrographs and SigmaScan® software and were determined to be 600 nm to 1.2 μm in diameter, which is optimal for deep-lung alveolar penetration. Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) were performed to analyze solid-state transitions and long-range molecular order, respectively, and allowed for the confirmation of the presence of phospholipid bilayers in the solid state of the particles. The residual water content of the particles was very low, as quantified analytically via Karl Fischer titration. The composition of the particles was confirmed using attenuated total-reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy and confocal Raman microscopy (CRM), and chemical imaging confirmed the chemical homogeneity of the particles. The dry powder aerosol dispersion properties were evaluated using the Next Generation Impactor™ (NGI™) coupled with the HandiHaler® dry powder inhaler device, where the mass median aerodynamic diameter from 2.6 to 4.3 μm with excellent aerosol dispersion performance, as exemplified by high values of emitted dose, fine particle fraction, and respirable fraction. Overall, it was determined that the pump rates defined in the spray-drying process had a significant effect on the solid-state particle properties and that a higher pump rate produced the most optimal system. Advanced dry powder inhalers of inhalable lipopolymers for targeted dry powder inhalation delivery were successfully achieved. PMID:23355776

Peri-implant stress correlates with bone and cement morphology: Micro-FE modeling of implanted cadaveric glenoids.

PubMed

Wee, Hwabok; Armstrong, April D; Flint, Wesley W; Kunselman, Allen R; Lewis, Gregory S

2015-11-01

Aseptic loosening of cemented joint replacements is a complex biological and mechanical process, and remains a clinical concern especially in patients with poor bone quality. Utilizing high resolution finite element analysis of a series of implanted cadaver glenoids, the objective of this study was to quantify relationships between construct morphology and resulting mechanical stresses in cement and trabeculae. Eight glenoid cadavers were implanted with a cemented central peg implant. Specimens were imaged by micro-CT, and subject-specific finite element models were developed. Bone volume fraction, glenoid width, implant-cortex distance, cement volume, cement-cortex contact, and cement-bone interface area were measured. Axial loading was applied to the implant of each model and stress distributions were characterized. Correlation analysis was completed across all specimens for pairs of morphological and mechanical variables. The amount of trabecular bone with high stress was strongly negatively correlated with both cement volume and contact between the cement and cortex (r = -0.85 and -0.84, p < 0.05). Bone with high stress was also correlated with both glenoid width and implant-cortex distance. Contact between the cement and underlying cortex may dramatically reduce trabecular bone stresses surrounding the cement, and this contact depends on bone shape, cement amount, and implant positioning. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Bowel preparation for colonoscopy with magnesium sulphate and low-volume polyethylene glycol.

PubMed

Tepeš, Bojan; Mlakar, Dominika N; Metličar, Tanja

2014-06-01

Patient compliance with bowel cleansing procedures represents one of the most objectionable aspects of colonoscopy. Adverse reactions to the purgative may result in failure to complete the preparation, inadequate visualization of the colon, polyp and even carcinoma miss rate and unwillingness to attend a follow-up colonoscopy. The primary objective of the study was to evaluate the effectiveness of bowel cleansing with magnesium sulphate and low-volume polyethylene glycol (PEG) with electrolytes. The second objective was to evaluate whether bowel cleansing was better in participants scheduled for morning colonoscopies or afternoon colonoscopies. Magnesium sulphate mineral water (2 l) and 2 l of low-volume PEG and electrolytes solution were used as our bowel cleansing protocol. A total of 13 914 participants, who participated in the Slovenian colorectal cancer screening programme in the period between 2009 and 2011, were included. Excellent bowel preparation was achieved in 11 484 (82.61%) participants; 1894 (13.62%) participants had good bowel preparation, 439 (3.16%) participants had fair bowel preparation and 85 (0.61%) participants had poor bowel preparation. Better results were achieved in the afternoon colonoscopies and in younger participant groups (P<0.001). No serious side effects of bowel cleansing were reported. This is the first study to use magnesium sulphate mineral water and PEG plus electrolytes for bowel cleansing. We found excellent bowel cleansing in 82.61% participants and in more participants if colonoscopy was performed in the afternoon.

Rotavirus-like particles primary recovery from insect cells in aqueous two-phase systems.

PubMed

Benavides, Jorge; Mena, Jimmy A; Cisneros-Ruiz, Mayra; Ramírez, Octavio T; Palomares, Laura A; Rito-Palomares, Marco

2006-09-14

Virus-like particles have a wide range of applications, including vaccination, gene therapy, and even as nanomaterials. Their successful utilization depends on the availability of selective and scalable methods of product recovery and purification that integrate effectively with upstream operations. In this work, a strategy based on aqueous two phase system (ATPS) was developed for the recovery of double-layered rotavirus-like particles (dlRLP) produced by the insect cell-baculovirus expression system. Polyethylene glycol (PEG) molecular mass, PEG and salt concentrations, and volume ratio (Vr, volume of top phase/volume of bottom phase) were evaluated in order to determine the conditions where dlRLP and contaminants concentrated to opposite phases. Two-stage ATPS consisting of PEG 400-phosphate with a Vr of 13.0 and a tie-line length (TLL) of 35% (w/w) at pH 7.0 provided the best conditions for processing highly concentrated crude extract from disrupted cells (dlRLP concentration of 5 microg/mL). In such conditions intracellular dlRLP accumulated in the top phase (recovery of 90%), whereas cell debris remained in the interface. Furthermore, dlRLP from culture supernatants accumulated preferentially in the interface (recovery of 82%) using ATPS with a Vr of 1.0, pH of 7.0, PEG 3350 (10.1%, w/w) and phosphate (10.9%, w/w). The purity of dlRLP from culture supernatant increased up to 55 times after ATPS. The use of ATPS resulted in a recovery process that produced dlRLP with a purity between 6 and 11% and an overall product yield of 85% (w/w), considering purification from intracellular and extracellular dlRLP. Overall, the strategy proposed in this study is simpler than traditional methods for recovering dlRLP, and represents a scalable and economically viable alternative for production processes of vaccines against rotavirus infection with significant scope for generic commercial application.

Preoperative Mechanical Bowel Evacuation Reduces Intraoperative Bleeding and Operation Time in Spinal Surgery.

PubMed

Rezvani, Majid; Abbasi, Reza; Tabesh, Homayoon; Dehghani, Leila; Dolatkhah, Shahab; Nasri, Maryam; Kolahdouzan, Mohsen; Meamar, Rokhsareh

2018-06-01

Randomized clinical trial. In this study, we evaluated the effect of mechanical evacuation of the bowels prior to operation on intraoperative bleeding. Bleeding is the most significant complication in patients undergoing spinal surgery. We randomly divided 108 individuals planned to undergo spinal surgery into two age-, sex-, and co-morbidity (especially preoperative hemoglobin [Hb])-matched groups of 54. The treatment group was administered polyethylene glycol (PEG) before the operation, whereas the control group was not. The exact amount (mL) of bleeding during operation, operative time, and approximate amount of blood transfused were recorded. The volume of bleeding and Hb level were also recorded 24 and 48 hours postoperatively. T -tests revealed that intraoperative bleeding, the volume of transfusion, and operative time were significantly lower in the treatment group than in the control group. Statistically significant correlations of intraoperative bleeding with age, body mass index (BMI), preoperative Hb levels, operative time, the volume of transfusion, hospitalization time, and 24- and 48-hour postoperative bleeding were observed ( p =0.001, all). Repeated measures analysis of covariance after adjusting the covariate variables revealed that the volume of bleeding showed a near-significant trend in the treatment group compared with that in the control group ( p =0.056). Diabetic females had the highest bleeding amount between the groups ( p =0.03). Bleeding was higher in patients with higher BMI ( p =0.02) and was related to operative time ( p =0.001) in both the groups. Preoperative gastrointestinal tract evacuation by PEG administration can decrease intraoperative bleeding in spinal surgeries; however, more research is imperative regarding PEG administration in surgical procedures for this purpose.

Core-shell microstructured nanocomposites for synergistic adjustment of environmental temperature and humidity

NASA Astrophysics Data System (ADS)

Zhang, Haiquan; Yuan, Yanping; Zhang, Nan; Sun, Qingrong; Cao, Xiaoling

2016-11-01

The adjustment of temperature and humidity is of great importance in a variety of fields. Composites that can perform both functions are prepared by mixing phase change materials (PCMs) with hygroscopic materials. However, the contact area between the adsorbent and humid air is inevitably decreased in such structures, which reduces the number of mass transfer channels for water vapor. An approach entailing the increase in the mass ratio of the adsorbent is presented here to improve the adsorption capacity. A core-shell CuSO4/polyethylene glycol (PEG) nanomaterial was developed to satisfy the conflicting requirements of temperature control and dehumidification. The results show that the equilibrium adsorption capacity of the PEG coating layer was enhanced by a factor of 188 compared with that of the pure PEG powder. The coating layer easily concentrates vapor, providing better adsorption properties for the composite. Furthermore, the volume modification of the CuSO4 matrix was reduced by 80% by the PEG coated layer, a factor that increases the stability of the composite. For the phase change process, the crystallization temperature of the coating layer was adjusted between 37.2 and 46.3 °C by interfacial tension. The core-shell CuSO4/PEG composite reported here provides a new general approach for the simultaneous control of temperature and humidity.

Achieving the best bowel preparation for colonoscopy

PubMed Central

Parra-Blanco, Adolfo; Ruiz, Alex; Alvarez-Lobos, Manuel; Amorós, Ana; Gana, Juan Cristóbal; Ibáñez, Patricio; Ono, Akiko; Fujii, Takahiro

2014-01-01

Bowel preparation is a core issue in colonoscopy, as it is closely related to the quality of the procedure. Patients often find that bowel preparation is the most unpleasant part of the examination. It is widely accepted that the quality of cleansing must be excellent to facilitate detecting neoplastic lesions. In spite of its importance and potential implications, until recently, bowel preparation has not been the subject of much study. The most commonly used agents are high-volume polyethylene glycol (PEG) electrolyte solution and sodium phosphate. There has been some confusion, even in published meta-analyses, regarding which of the two agents provides better cleansing. It is clear now that both PEG and sodium phosphate are effective when administered with proper timing. Consequently, the timing of administration is recognized as one of the central factors to the quality of cleansing. The bowel preparation agent should be administered, at least in part, a few hours in advance of the colonoscopy. Several low volume agents are available, and either new or modified schedules with PEG that usually improve tolerance. Certain adjuvants can also be used to reduce the volume of PEG, or to improve the efficacy of other agents. Other factors apart from the choice of agent can improve the quality of bowel cleansing. For instance, the effect of diet before colonoscopy has not been completely clarified, but an exclusively liquid diet is probably not required, and a low-fiber diet may be preferable because it improves patient satisfaction and the quality of the procedure. Some patients, such as diabetics and persons with heart or kidney disease, require modified procedures and certain precautions. Bowel preparation for pediatric patients is also reviewed here. In such cases, PEG remains the most commonly used agent. As detecting neoplasia is not the main objective with these patients, less intensive preparation may suffice. Special considerations must be made for patients with inflammatory bowel disease, including safety and diagnostic issues, so that the most adequate agent is chosen. Identifying neoplasia is one of the main objectives of colonoscopy with these patients, and the target lesions are often almost invisible with white light endoscopy. Therefore excellent quality preparation is required to find these lesions and to apply advanced methods such as chromoendoscopy. Bowel preparation for patients with lower gastrointestinal bleeding represents a challenge, and the strategies available are also reviewed here. PMID:25548470

Solid phase pegylation of hemoglobin.

PubMed

Suo, Xiaoyan; Zheng, Chunyang; Yu, Pengzhan; Lu, Xiuling; Ma, Guanghui; Su, Zhiguo

2009-01-01

A solid phase conjugation process was developed for attachment of polyethylene glycol to hemoglobin molecule. Bovine hemoglobin was loaded onto an ion exchange chromatography column and adsorbed by the solid medium. Succinimidyl carbonate mPEG was introduced in the mobile phase after the adsorption. Pegylation took place between the hemoglobin on the solid phase, and the pegylation reagent in the liquid phase. A further elution was carried out to separate the pegylated and the unpegylated protein. Analysis by HPSEC, SDS-PAGE, and MALLS demonstrated that the fractions eluted from the solid phase contained well-defined components. Pegylated hemoglobin with one PEG chain was obtained with the yield of 75%, in comparison to the yield of 30% in the liquid phase pegylation. The P(50) values of the mono-pegylated hemoglobin, prepared with SC-mPEG 5 kDa, 10 kDa and 20 kDa, were 19.97, 20.23 and 20.54 mmHg, which were much closer to the value of red blood cells than that of pegylated hemoglobin prepared with the conventional method.

Measurements of Attractive Forces between Proteins and End-Grafted Poly(Ethylene Glycol) Chains

NASA Astrophysics Data System (ADS)

Sheth, S. R.; Leckband, D.

1997-08-01

The surface force apparatus was used to measure directly the molecular forces between streptavidin and lipid bilayers displaying grafted Mr 2,000 poly(ethylene glycol) (PEG). These measurements provide direct evidence for the formation of relatively strong attractive forces between PEG and protein. At low compressive loads, the forces were repulsive, but they became attractive when the proteins were pressed into the polymer layer at higher loads. The adhesion was sufficiently robust that separation of the streptavidin and PEG uprooted anchored polymer from the supporting membrane. These interactions altered the properties of the grafted chains. After the onset of the attraction, the polymer continued to bind protein for several hours. The changes were not due to protein denaturation. These data demonstrate directly that the biological activity of PEG is not due solely to properties of simple polymers such as the excluded volume. It is also coupled to the competitive interactions between solvent and other materials such as proteins for the chain segments and to the ability of this material to adopt higher order intrachain structures.

A thermosensitive hydrogel based on biodegradable amphiphilic poly(ethylene glycol) polycaprolactone poly(ethylene glycol) block copolymers

NASA Astrophysics Data System (ADS)

Gong, Chang Yang; Qian, Zhi Yong; Liu, Cai Bing; Juan Huang, Mei; Gu, Ying Chun; Wen, Yan Jun; Kan, Bing; Wang, Ke; Dai, Mei; Li, Xing Yi; Gou, Ma Ling; Tu, Ming Jing; Wei, Yu Quan

2007-06-01

A series of low molecular weight poly(ethylene glycol)-polycaprolactone-poly(ethylene glycol) (PEG-PCL-PEG) biodegradable block copolymers were successfully synthesized using isophorone diisocyanate (IPDI) as the coupling agent, and were characterized using 1H NMR and Fourier transform infrared spectroscopy. The aqueous solutions of the PEG-PCL-PEG copolymers displayed a special thermosensitive gel-sol transition when the concentration was above the corresponding critical gel concentration. Gel-sol phase diagrams were recorded using the test-tube-inversion method; they depended on the hydrophilic/hydrophobic balance in the macromolecular structure, as well as some other factors, including the heating history, volume, and the ageing time of the copolymer aqueous solutions and dissolution temperature of the copolymers. As a result, the gel-sol transition temperature range could be altered, which might be very useful for application in injectable drug delivery systems. This work was financially supported by the Chinese Key Basic Research Program (2004CB518800 and 2004CB518807), and the Sichuan Key Project of Science and Technology (06(05SG022-021-02)).

Volumetric Properties, Viscosities, and Refractive Indices of the Binary Systems 1-Butanol + PEG 200, + PEG 400, and + TEGDME

NASA Astrophysics Data System (ADS)

Živković, N.; Šerbanović, S.; Kijevčanin, M.; Živković, E.

2013-06-01

Densities, viscosities, and refractive indices of three binary systems consisting of 1-butanol with polyethylene glycols of different molecular weights (PEG 200 and PEG 400) or tetraethylene glycol dimethyl ether (TEGDME) were measured at ten temperatures (288.15, 293.15, 298.15, 303.15, 308.15, 313.15, 318.15, 323.15, 328.15, and 333.15) K and atmospheric pressure. Densities of the selected binary mixtures were measured with an Anton Paar DMA 5000 digital vibrating U-tube densimeter, refractive indices were measured with an automatic Anton Paar RXA-156 refractometer, while for viscosity measurements, a digital Stabinger SVM 3000/G2 viscometer was used. From these data, excess molar volumes were calculated and fitted to the Redlich-Kister equation. The obtained results have been analyzed in terms of specific molecular interactions and mixing behavior between mixture components, as well as the influence of temperature on them. Viscosity data were also correlated by Grunberg-Nissan, Eyring-UNIQUAC, three-body McAlister, and Eyring-NRTL models.

Suitability of polymer materials for production of pulmonary microparticles using a PGSS supercritical fluid technique: thermodynamic behaviour of fatty acids, PEGs and PEG-fatty acids.

PubMed

Vijayaraghavan, Meera; Stolnik, Snjezana; Howdle, Steven M; Illum, Lisbeth

2012-11-15

The thermodynamic behaviour of selected polymeric components for preparation of controlled release microparticles using supercritical carbon dioxide (scCO(2)) processing was investigated. The polymeric materials selected were egg lecithin (a model for the lung surfactant phospholipid), poly(ethyleneglycol) (PEG) of different molecular weights, fatty acids (C18, C16, and C14), and physical blends of PEGs and fatty acids. In addition a range of PEG-stearates was also assessed. Analysis of thermodynamic behaviour was performed by differential scanning calorimetry (DSC) and by assessment of their interaction with scCO(2) in a high-pressure variable volume view cell. The key criterion was to demonstrate a strong interaction with scCO(2) and to show liquefaction of the polymeric material at acceptable processing temperatures and pressures. Positive results should then indicate the suitability of these materials for processing by the Particle from Gas Saturated Solutions (PGSS) technique using scCO(2) to create microparticles for pulmonary administration. It was found that the materials tested interacted with scCO(2) and showed a sufficient lowering of their melting temperature (T(m)) to make them suitable for use in the PGSS microparticle production rig. Fatty acids of low T(m) were shown to act as a plasticising agent and to lower the T(m) of PEG further during interaction with scCO(2). Copyright © 2012 Elsevier B.V. All rights reserved.

Use of fractional laser microablation of skin for improvement of its immersion clearing

NASA Astrophysics Data System (ADS)

Kolesnikova, Ekaterina A.; Kolesnikov, Aleksandr S.; Genina, Elina A.; Dolotov, Leonid E.; Tuchina, Darya K.; Bashkatov, Alexey N.; Tuchin, Valery V.

2013-02-01

We are proposing a new method for enhancement of optical clearing agent delivery into the skin using fractional laser microablation of the skin surface. The Palomar Lux2940 erbium laser with the wavelength 2940 nm and pulse duration of 5 ms was used as a light source. Two regimes of laser action were used in the experiments: the first one realized microablation of skin upper layer and the second one created microchannels in skin. As optical clearing agents mineral oil and PEG-300 were used. In vivo studies were carried out with white outbred rats. Both parameters: the permeability coefficient of the agents in the tissue and the optical probing depth were measured using the OCT system at a wavelength of 930 nm. The following values of the permeability coefficient of the skin with microablation were obtained: (3.41+/-0.46)×10-5 cm/s and (2.35+/-0.30)×10-5 cm/s for mineral oil and PEG-300, respectively, at the use of the surface microablation and (3.32+/-0.09)×10-5 cm/s and (3.61+/-0.34)×10-5 cm/s for mineral oil and PEG-300, respectively, at the use of the microporation. The results have shown that the joint application of mineral oil with microablation in the first regime promotes maximal (nearly 2-folds) increasing of optical probing depth in 30 min. Obtained data can be used for development of optical diagnostic methods of skin diseases.

Refolding of laccase from Trametes versicolor using aqueous two phase systems: Effect of different additives.

PubMed

Sánchez-Trasviña, Calef; Mayolo-Deloisa, Karla; González-Valdez, José; Rito-Palomares, Marco

2017-07-21

Protein refolding is a strategy used to obtain active forms of proteins from inclusion bodies. On its part, laccase is an enzyme with potential for different biotechnological applications but there are few reports regarding its refolding which in many cases is considered inefficient due to the poor obtained refolding yields. Aqueous Two-Phase Systems (ATPS) have been used for the refolding of proteins getting acceptable recovery percentages since PEG presents capacity to avoid protein aggregation. In this work, 48 PEG-phosphate ATPS were analyzed to study the impact of different parameters (i.e. tie line length (TLL), volume ratio (V R ) and PEG molecular weight) upon the recovery and refolding of laccase. Additionally, since laccase is a metalloprotein, the use of additives (individually and in mixture) was studied with the aim of favoring refolding. Results showed that laccase presents a high affinity for the PEG-rich phase obtaining recovery values of up to 90%. Such affinity increases with increasing TLL and decreases when PEG molecular weight and V R increase. In denatured state, this PEG-rich phase affinity decreases drastically. However, the use of additives such as l-cysteine, glutathione oxidized, cysteamine and Cu +2 was critical in improving refolding yield values up to 100%. The best conditions for the refolding of laccase were obtained using the PEG 400gmol -1 , TLL 45% w/w, V R 3 ATPS and a mixture of 2.5mM cysteamine with 1mM Cu +2 . To our knowledge, this is the first time that the use of additives and the behavior of the mixture of such additives to enhance refolding performance in ATPS is reported. Copyright © 2017 Elsevier B.V. All rights reserved.

Physical controls on directed virus assembly at nanoscale chemical templates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheung, C L; Chung, S; Chatterji, A

2006-05-10

Viruses are attractive building blocks for nanoscale heterostructures, but little is understood about the physical principles governing their directed assembly. In-situ force microscopy was used to investigate organization of Cowpea Mosaic Virus engineered to bind specifically and reversibly at nanoscale chemical templates with sub-30nm features. Morphological evolution and assembly kinetics were measured as virus flux and inter-viral potential were varied. The resulting morphologies were similar to those of atomic-scale epitaxial systems, but the underlying thermodynamics was analogous to that of colloidal systems in confined geometries. The 1D templates biased the location of initial cluster formation, introduced asymmetric sticking probabilities, andmore » drove 1D and 2D condensation at subcritical volume fractions. The growth kinetics followed a t{sup 1/2} law controlled by the slow diffusion of viruses. The lateral expansion of virus clusters that initially form on the 1D templates following introduction of polyethylene glycol (PEG) into the solution suggests a significant role for weak interaction.« less

Efflorescence of ammonium sulfate and coated ammonium sulfate particles: evidence for surface nucleation.

PubMed

Ciobanu, V Gabriela; Marcolli, Claudia; Krieger, Ulrich K; Zuend, Andreas; Peter, Thomas

2010-09-09

Using optical microscopy, we investigated the efflorescence of ammonium sulfate (AS) in aqueous AS and in aqueous 1:1 and 8:1 (by dry weight) poly(ethylene glycol)-400 (PEG-400)/AS particles deposited on a hydrophobically coated slide. Aqueous PEG-400/AS particles exposed to decreasing relative humidity (RH) exhibit a liquid-liquid phase separation below approximately 90% RH with the PEG-400-rich phase surrounding the aqueous AS inner phase. Pure aqueous AS particles effloresced in the RH range from 36.3% to 43.7%, in agreement with literature data (31-48% RH). In contrast, aqueous 1:1 (by dry weight) PEG-400/AS particles with diameters of the AS phase from 7.2 to 19.2 mum effloresced between 26.8% and 33.9% RH and aqueous 8:1 (by dry weight) PEG-400/AS particles with diameters of the AS phase from 1.8 to 7.3 mum between 24.3% and 29.3% RH. Such low efflorescence relative humidity (ERH) values have never been reached before for AS particles of this size range. We show that these unprecedented low ERHs of AS in PEG-400/AS particles could not possibly be explained by the presence of low amounts of PEG-400 in the aqueous AS phase, by a potential inhibition of water evaporation via anomalously slow diffusion through the PEG coating, or by different time scales between various experimental techniques. High-speed photography of the efflorescence process allowed the development of the AS crystallization fronts within the particles to be monitored with millisecond time resolution. The nucleation sites were inferred from the initial crystal growth sites. Analysis of the probability distribution of initial sites of 31 and 19 efflorescence events for pure AS and 1:1 (by dry weight) PEG-400/AS particles, respectively, showed that the particle volume can be excluded as the preferred nucleation site in the case of pure AS particles. For aqueous 1:1 (by dry weight) PEG-400/AS particles preferential AS nucleation in the PEG phase and at the PEG/AS/substrate contact line can be excluded. On the basis of this probability analysis of efflorescence events together with the AS ERH values of pure aqueous AS and aqueous PEG-400/AS particles aforementioned, we suggest that in pure aqueous AS particles nucleation starts at the surface of the particles and attribute the lower ERH values observed for aqueous PEG-400/AS particles to the suppression of the surface-induced nucleation process. Our results suggest that surface-induced nucleation is likely to also occur during the efflorescence of atmospheric AS aerosol particles, possibly constituting the dominating nucleation pathway.

Chemical composition and the nutritive value of pistachio epicarp (in situ degradation and in vitro gas production techniques).

PubMed

Bakhshizadeh, Somayeh; Taghizadeh, Akbar; Janmohammadi, Hossein; Alijani, Sadegh

2014-01-01

The nutritive value of pistachio epicarp (PE) was evaluated by in situ and in vitro techniques. Chemical analysis indicated that PE was high in crude protein (11.30%) and low in neutral detergent fiber (26.20%). Total phenols, total tannins, condensed tannins and hydrolysable tannins contents in PE were 8.29%, 4.48%, 0.49% and 3.79%, respectively. Ruminal dry matter and crude protein degradation after 48 hr incubation were 75.21% and 82.52%, respectively. The gas production volume at 48 hr for PE was 122.47 mL g(-1)DM. As a whole, adding polyethylene glycol (PEG) to PE increased (p < 0.05) gas production volumes, organic matter digestibility and the metabolizable energy that illustrated inhibitory effect of phenolics on rumen microbial fermentation and the positive influence of PEG on digestion PE. The results showed that PE possessed potentials to being used as feed supplements.

Solubility and thermodynamics of apremilast in different mono solvents: Determination, correlation and molecular interactions.

PubMed

Shakeel, Faiyaz; Haq, Nazrul; Alanazi, Fars K; Alsarra, Ibrahim A

2017-05-15

The solubility data of recently launched poorly soluble antipsoriatic drug apremilast (APM) in any mono solvent or cosolvent mixtures with respect to temperature are not available in literature. Hence, in this research work, the solubility of APM in twelve different mono solvents namely "water, methanol, ethanol, isopropanol (IPA), ethylene glycol (EG), propylene glycol (PG), 1-butanol, 2-butanol, ethyl acetate (EA), dimethyl sulfoxide (DMSO), polyethylene glycol-400 (PEG-400) and Transcutol ® " was determined at temperatures "T=298.2K to 318.2K" and pressure "p=0.1 MPa". Eexperimental solubilities of APM in mole fraction were determined by a static equilibrium method using high performance liquid chromatography at 254nm. Experimental solubilities of APM in mole fraction were correlated well with "Van't Hoff and Apelblat models". The solubilities of APM in mole fraction were recorded highest in DMSO (9.91×10 -2 ), followed by EA (2.54×10 -2 ), Transcutol (2.51×10 -2 ), PEG-400 (2.16×10 -2 ),PG (4.01×10 -3 ), EG (1.61×10 -3 ), IPA (4.96×10 -4 ), 1-butanol (4.18×10 -4 ), 2-butanol (3.91×10 -4 ), methanol (2.25×10 -4 ), ethanol (2.20×10 -4 ) and water (1.29×10 -6 ) at "T=318.2K" and similar results were also obtained at each temperature evaluated. The molecular interactions between solute and solvent molecules were evaluated by the determination of activity coefficients. Based on activity coefficients, the higher solute-solvents molecular interactions were recorded in APM-DMSO, APM-EA, APM-Transcutol and APM-PEG-400 in comparison with other combination of solute and solvents. "Apparent standard thermodynamic parameters" of APM indicated an "endothermic and entropy-driven dissolution" of APM in all mono solvents evaluated. Based on these results, APM was proposed as freely soluble in DMSO, EA and Transcutol, sparingly soluble in PEG0-400, slightly soluble in methanol, ethanol, IPA, EG, PG, 1-butanol and 2-butanol and practically insoluble in water. Hence, DMSO, EA and Transcutol were selected as the best solvents and water and ethanol were selected as the anti-solvents for APM. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of macromolecular crowding on the structure of the protein complex superoxide dismutase

NASA Astrophysics Data System (ADS)

Rajapaksha Mudalige, Ajith Rathnaweera

Biological environments contain between 7 - 40% macromolecules by volume. This reduces the available volume for macromolecules and elevates the osmotic pressure relative to pure water. Consequently, biological macromolecules in their native environments tend to adopt more compact and dehydrated conformations than those in vitro. This effect is referred to as macromolecular crowding and constitutes an important physical difference between native biological environments and the simple solutions in which biomolecules are usually studied. We used small angle scattering (SAS) to measure the effects of macromolecular crowding on the size of a protein complex, superoxide dismutase (SOD). Crowding was induced using 400 MW polyethylene glycol (PEG), triethylene glycol (TEG), methyl-alpha-glucoside (alpha-MG) and trimethylamine N-oxide (TMAO). Parallel small angle neutron scattering (SANS) and small angle X-ray scattering (SAXS) allowed us to unambiguously attribute apparent changes in radius of gyration to changes in the structure of SOD. For a 40% PEG solution, we find that the volume of SOD was reduced by 9%. SAS coupled with osmotic pressure measurements allowed us to estimate a compressibility modulus for SOD. We believe this to be the first time the osmotic compressibility of a protein complex was measured. Molecular Dynamics (MD) simulations are widely used to obtain insights on biomolecular processes. However, it is not clear whether MD is capable of predicting subtle effects of macromolecular crowding. We used our experimentally observed compressibility of SOD to evaluate the ability of MD to predict macromolecular crowding. Effects of macromolecular crowding due to PEG on SOD were modeled using an all atom MD simulation with the CHARMM forcefield and the crystallographically resolved structures of SOD and PEG. Two parallel MD simulations were performed for SOD in water and SOD in 40% PEG for over 150~ns. Over the period of the simulation the SOD structure in 40% PEG did not change compared to the SOD structure in water. It therefore appears that under the conditions of our simulations MD could not describe the experimentally observed effects of macromolecular crowding. In a separate project, we measured the rate of diffusive transport in excised porcine corneal stroma using FCS for fluorescent labeled dextran molecules with hydrodynamic radii ranging from 1.3 to 34 nm. Dextran molecules diffuse more slowly in cornea as compared to buffer solution. The reduction in diffusion coefficient is modest however (67% smaller), and is uniform over the range of sizes that we measured. Diffusion coefficients measured parallel vs. perpendicular to the collagen lamellae were indistinguishable. This indicates that diffusion in the corneal stroma is not highly anisotropic. Delivery of therapeutic agents to the eye requires efficient transport through cellular and extracellular barriers. Our measurements bring important insights into how macromolecular and nanoparticle therapeutics might permeate through the eyes.

Suspended Microchannel Resonators for Ultralow Volume Universal Detection

PubMed Central

Son, Sungmin; Grover, William H.; Burg, Thomas P.; Manalis, Scott R.

2008-01-01

Universal detectors that maintain high sensitivity as the detection volume is reduced to the subnanoliter scale can enhance the utility of miniaturized total analysis systems (μ-TAS). Here the unique scaling properties of the suspended microchannel resonator (SMR) are exploited to show universal detection in a 10 pL analysis volume with a density detection limit of ∼1 μg/cm3 (10 Hz bandwidth) and a dynamic range of 6 decades. Analytes with low UV extinction coefficients such as polyethylene glycol (PEG) 8 kDa, glucose, and glycine are measured with molar detection limits of 0.66, 13.5, and 31.6 μM, respectively. To demonstrate the potential for real-time monitoring, gel filtration chromatography was used to separate different molecular weights of PEG as the SMR acquired a chromatogram by measuring the eluate density. This work suggests that the SMR could offer a simple and sensitive universal detector for various separation systems from liquid chromatography to capillary electrophoresis. Moreover, since the SMR is itself a microfluidic channel, it can be directly integrated into μ-TAS without compromising overall performance. PMID:18489125

Comparative study on digestive lipase activities on the self emulsifying excipient Labrasol, medium chain glycerides and PEG esters.

PubMed

Fernandez, Sylvie; Jannin, Vincent; Rodier, Jean-David; Ritter, Nicolas; Mahler, Bruno; Carrière, Frédéric

2007-05-01

Labrasol is a lipid-based self-emulsifying excipient used in the preparation of lipophilic drugs intended for oral delivery. It is mainly composed of PEG esters and glycerides with medium acyl chains, which are potential substrates for digestive lipases. The hydrolysis of Labrasol by porcine pancreatic extracts, human pancreatic juice and several purified digestive lipases was investigated in the present study. Classical human pancreatic lipase (HPL) and porcine pancreatic lipase, which are the main lipases involved in the digestion of dietary triglycerides, showed very low levels of activity on the entire Labrasol excipient as well as on separated fractions of glycerides and PEG esters. On the other hand, gastric lipase, pancreatic lipase-related protein 2 (PLRP2) and carboxyl ester hydrolase (CEH) showed high specific activities on Labrasol. These lipases were found to hydrolyze the main components of Labrasol (PEG esters and monoglycerides) used as individual substrates, whereas these esters were found to be poor substrates for HPL. The lipolytic activity of pancreatic extracts and human pancreatic juice on Labrasol(R) is therefore mainly due to the combined action of CEH and PLRP2. These two pancreatic enzymes, together with gastric lipase, are probably the main enzymes involved in the in vivo lipolysis of Labrasol taken orally.

Development practices and lessons learned in developing SimPEG

NASA Astrophysics Data System (ADS)

Cockett, R.; Heagy, L. J.; Kang, S.; Rosenkjaer, G. K.

2015-12-01

Inverse modelling provides a mathematical framework for constructing a model of physical property distributions in the subsurface that are consistent with the data collected in geophysical surveys. The geosciences are increasingly moving towards the integration of geological, geophysical, and hydrological information to better characterize the subsurface. This integration must span disciplines and is not only challenging scientifically, but additionally the inconsistencies between conventions often makes implementations complicated, non­ reproducible, or inefficient. SimPEG is an open-source, multi-university effort aimed at providing a generalized framework for solving forward and inverse problems. SimPEG includes finite volume discretizations on structured and unstructured meshes, interfaces to standard numerical solver packages, convex optimization algorithms, model parameterizations, and visualization routines. The SimPEG package (http://simpeg.xyz) supports an ecosystem of forward and inverse modelling applications, including electromagnetics, vadose zone flow, seismic, and potential­ fields, that are all written with a common interface and toolbox. The goal of SimPEG is to support a community of researchers with well-tested, extensible tools, and encourage transparency and reproducibility both of the SimPEG software and the geoscientific research it is applied to. In this presentation, we will share some of the lessons we have learned in designing the modular infrastructure, testing and development practices of SimPEG. We will discuss our use of version control, extensive unit-testing, continuous integration, documentation, issue tracking, and resources that facilitate communication between existing team members and allows new researchers to get involved. These practices have enabled the use of SimPEG in research, industry, and education as well as the ability to support a growing number of dependent repositories and applications. We hope that sharing our practices and experiences will help other researchers who are creating communities around their own scientific software. As this session suggests, "software is critical to the success of science," but, it is the *communities* of researchers that must be supported as we strive to create top quality research tools.

A review of current issues underlying colon cleansing before colonoscopy

PubMed Central

Hookey, Lawrence C; Vanner, Stephen

2007-01-01

The present review examines four current issues related to the efficacy, patient tolerance and safety of the following bowel cleansing agents: oral sodium phosphate (NaP), polyethylene glycol (PEG) and magnesium citrate (Pico-Salax, Ferring Pharmaceuticals Inc, Canada), an agent recently made available in Canada. MedLine and PubMed databases were systematically searched to identify studies related to the efficacy of altered PEG solutions combined with adjunct treatments; the efficacy, tolerability and safety of Pico-Salax; the association between nephrocalcinosis, and chronic renal failure and oral NaP use; and the role of diet. Although lower volume PEG solutions combined with adjuvant agents were generally associated with better patient tolerance, their efficacy was varied and interpretation of this end point is complicated by study design issues. There are very few reported studies of Pico-Salax, and as a result, there are insufficient data to draw conclusions about the efficacy of this agent. The available data suggest that Pico-Salax may be better tolerated by patients, than oral NaP and PEG solutions. There is a paucity of hemodynamic monitoring data pre- and postadministration, but the available data suggests that this small-volume osmotic agent could cause subclinical contraction of the intravascular space. Recent case reports suggest an association between nephrocalcinosis and oral NaP ingestion, but to date, these reports have been confined to a single centre. Preliminary studies suggest that this is not a widespread problem, but more studies are needed. There are only a few studies examining diet and patient tolerability, but they do suggest that diet may be liberalized with some cleansing regimens to enhance tolerability without decreasing efficacy. The present review highlights current controversies and advances in colon cleansing before colonoscopy, and also identifies areas for further study. PMID:17299615

Detection methods for human enteric viruses in representative foods.

PubMed

Leggitt, P R; Jaykus, L A

2000-12-01

Although viral foodborne disease is a significant problem, foods are rarely tested for viral contamination, and when done, testing is limited to shellfish commodities. In this work, we report a method to extract and detect human enteric viruses from alternative food commodities using an elution-concentration approach followed by detection using reverse transcription-polymerase chain reaction (RT-PCR). Fifty-gram lettuce or hamburger samples were artificially inoculated with poliovirus type 1 (PV1), hepatitis A virus (HAV), or the Norwalk virus and processed by the sequential steps of homogenization, filtration, Freon extraction (hamburger), and polyethylene glycol (PEG) precipitation. To reduce volumes further and remove RT-PCR inhibitors, a secondary PEG precipitation was necessary, resulting in an overall 10- to 20-fold sample size reduction from 50 g to 3 to 5 ml. Virus recoveries in secondary PEG concentrates ranged from 10 to 70% for PV1 and 2 to 4% for HAV as evaluated by mammalian cell culture infectivity assay. Total RNA from PEG concentrates was extracted to a small volume (30 to 40 microl) and subjected to RT-PCR amplification of viral RNA sequences. Detection limit studies indicated that viral RNA was consistently detected by RT-PCR at initial inoculum levels > or =102 PFU/50-g food sample for PV1 and > or =10(3) PFU/50-g food sample for HAV. In similar studies with the Norwalk virus, detection at inoculum levels > or =1.5 X 10(3) PCR-amplifiable units/50-g sample for both food products was possible. All RT-PCR amplicons were confirmed by subsequent Southern hybridization. The procedure reported represents progress toward the development of methods to detect human enteric viral contamination in foods other than shellfish.

A trifunctional multi-walled carbon nanotubes/polyethylene glycol (MWCNT/PEG)-coated separator through a layer-by-layer coating strategy for high-energy Li–S batteries

DOE PAGES

Luo, Liu; Chung, Sheng-Heng; Manthiram, Arumugam

2016-10-11

In this study, a trifunctional separator fabricated by using a light-weight layer-by-layer multi-walled carbon nanotubes/polyethylene glycol (MWCNT/PEG) coating has been explored in lithium–sulfur (Li–S) batteries. The conductive MWCNT/PEG coating serves as (i) an upper current collector for accelerating the electron transport and benefiting the electrochemical reaction kinetics of the cell, (ii) a net-like filter for blocking and intercepting the migrating polysulfides through a synergistic effect including physical and chemical interactions, and (iii) a layered barrier for inhibiting the continuous diffusion and alleviating the volume change of the trapped active material by introducing a “buffer zone” in between the coated layers.more » The multi-layered MWCNT/PEG coating allows the use of the conventional pure sulfur cathode with a high sulfur content (78 wt%) and high sulfur loading (up to 6.5 mg cm -2) to achieve a high initial discharge capacity of 1206 mA h g -1 at C/5 rate, retaining a superior capacity of 630 mA h g -1 after 300 cycles. Lastly, the MWCNT/PEG-coated separator optimized by the facile layer-by-layer coating method provides a promising and feasible option for advanced Li–S batteries with high energy density.« less

A superactive leptin antagonist alters metabolism and locomotion in high-leptin mice.

PubMed

Chapnik, Nava; Solomon, Gili; Genzer, Yoni; Miskin, Ruth; Gertler, Arieh; Froy, Oren

2013-06-01

Transgenic alpha murine urokinase-type plasminogen activator (αMUPA) mice are resistant to obesity and their locomotor activity is altered. As these mice have high leptin levels, our objective was to test whether leptin is responsible for these characteristics. αMUPA, their genetic background control (FVB/N), and C57BL mice were injected s.c. every other day with 20  mg/kg pegylated superactive mouse leptin antagonist (PEG-SMLA) for 6 weeks. We tested the effect of PEG-SMLA on body weight, locomotion, and bone health. The antagonist led to a rapid increase in body weight and subsequent insulin resistance in all treated mice. Food intake of PEG-SMLA-injected animals increased during the initial period of the experiment but then declined to a similar level to that of the control animals. Interestingly, αMUPA mice were found to have reduced bone volume (BV) than FVB/N mice, although PEG-SMLA increased bone mass in both strains. In addition, PEG-SMLA led to disrupted locomotor activity and increased corticosterone levels in C57BL but decreased levels in αMUPA or FVB/N mice. These results suggest that leptin is responsible for the lean phenotype and reduced BV in αMUPA mice; leptin affects corticosterone levels in mice in a strain-specific manner; and leptin alters locomotor activity, a behavior determined by the central circadian clock.

Core-shell microstructured nanocomposites for synergistic adjustment of environmental temperature and humidity

PubMed Central

Zhang, Haiquan; Yuan, Yanping; Zhang, Nan; Sun, Qingrong; Cao, Xiaoling

2016-01-01

The adjustment of temperature and humidity is of great importance in a variety of fields. Composites that can perform both functions are prepared by mixing phase change materials (PCMs) with hygroscopic materials. However, the contact area between the adsorbent and humid air is inevitably decreased in such structures, which reduces the number of mass transfer channels for water vapor. An approach entailing the increase in the mass ratio of the adsorbent is presented here to improve the adsorption capacity. A core-shell CuSO4/polyethylene glycol (PEG) nanomaterial was developed to satisfy the conflicting requirements of temperature control and dehumidification. The results show that the equilibrium adsorption capacity of the PEG coating layer was enhanced by a factor of 188 compared with that of the pure PEG powder. The coating layer easily concentrates vapor, providing better adsorption properties for the composite. Furthermore, the volume modification of the CuSO4 matrix was reduced by 80% by the PEG coated layer, a factor that increases the stability of the composite. For the phase change process, the crystallization temperature of the coating layer was adjusted between 37.2 and 46.3 °C by interfacial tension. The core-shell CuSO4/PEG composite reported here provides a new general approach for the simultaneous control of temperature and humidity. PMID:27845371

Impact of the Quality of Bowel Cleansing on the Efficacy of Colonic Cancer Screening: A Prospective, Randomized, Blinded Study

PubMed Central

2015-01-01

Objectives Efficacy of two low volume bowel cleansing preparations, polyethylene glycol plus ascorbate (PEG+Asc) and sodium picosulfate/magnesium citrate (NaPic/MgCit), were compared for polyp and adenoma detection rate (PDR and ADR) and overall cleansing ability. Primary endpoint was PDR (the number of patients with ≥1 polypoid or flat lesion recorded by the colonoscopist). Methods Diagnostic, surveillance or screening colonoscopy patients were enrolled into this investigator-blinded, multi-center Phase IV study and randomized 1:1 to receive PEG+Asc (administered the evening before and the morning of colonoscopy, per label) or NaPic/MgCit (administered in the morning and afternoon the day before colonoscopy, per label). The blinded colonoscopist documented any lesion and assessed cleansing quality (Harefield Cleansing Scale). Results Of 394 patients who completed the study, 393 (PEG+Asc, N=200; NaPic/MgCit, N=193) had a colonoscopy. Overall PDR for PEG+Asc versus NaPic/MgCit was 51.5% versus 44.0%, p=0.139. PDR and ADR on the right side of the bowel were significantly higher with PEG+Asc versus NaPic/MgCit (PDR: 56[28.0%] versus 32[16.6%], p=0.007; ADR: 42[21.0%] versus 23[11.9%], p=0.015), as was detection of flat lesions (43[21.5%] versus 25[13.0%], p=0.025). Cleansing quality was better with PEG+Asc than NaPic/MgCit (98.5% versus 57.5% considered successful cleansing). Overall, there were 132 treatment-emergent adverse events (93 versus 39 for PEG+Asc and NaPic/MgCit, respectively). These were mainly mild abdominal symptoms, all of which were reported for higher proportions of patients in the PEG+Asc than NaPic/MgCit group. Twice as many patients in the NaPic/MgCit versus the PEG+Asc group reported tolerance of cleansing solution as ‘very good’. Conclusions Compared with NaPic/MgCit, PEG+Asc may be more efficacious for overall cleansing ability, and subsequent detection of right-sided and flat lesions. This is likely attributable to the different administration schedules of the two bowel cleansing preparations, which may positively impact the detection and prevention of colorectal cancer, thereby improving mortality rates. Trial Registration ClinicalTrials.gov NCT01689792. PMID:25950434

Colyte and Colyte-flavored (PEG-3350 & electrolytes) for oral solution for gastrointestinal lavage.

PubMed

Pickering, P

1994-06-01

Colyte and Colyte-flavored are effective in preparing the bowel for endoscopic examination, particularly when used in combination with saline and stimulant laxatives, which may decrease the volume of Colyte required for optimal bowel cleansing.

Theranostic probe for simultaneous in vivo photoacoustic imaging and confined photothermolysis by pulsed laser at 1064 nm in 4T1 breast cancer model

NASA Astrophysics Data System (ADS)

Zhou, Min; Ku, Geng; Pageon, Laura; Li, Chun

2014-11-01

Here, we report that polyethylene glycol (PEG)-coated copper(ii) sulfide nanoparticles (PEG-CuS NPs) with their peak absorption tuned to 1064 nm could be used both as a contrast agent for photoacoustic tomographic imaging of mouse tumor vasculature and as a mediator for confined photothermolysis of tumor cells in an orthotopic syngeneic 4T1 breast tumor model. PEG-CuS NPs showed stronger photoacoustic signal than hollow gold nanospheres and single-wall carbon nanotubes at 1064 nm. MicroPET imaging of 4T1 tumor-bearing mice showed a gradual accumulation of the NPs in the tumor over time. About 6.5% of injected dose were taken up in each gram of tumor tissue at 24 h after intravenous injection of 64Cu-labeled PEG-CuS NPs. For both photoacoustic imaging and therapeutic studies, nanosecond (ns)-pulsed laser was delivered with Q-switched Nd:YAG at a wavelength of 1064 nm. Unlike conventional photothermal ablation therapy mediated by continuous wave laser with which heat could spread to the surrounding normal tissue, interaction of CuS NPs with short pulsed laser deliver heat rapidly to the treatment volume keeping the thermal damage confined to the target tissues. Our data demonstrated that it is possible to use a single-compartment nanoplatform to achieve both photoacoustic tomography and highly selective tumor destruction at 1064 nm in small animals.Here, we report that polyethylene glycol (PEG)-coated copper(ii) sulfide nanoparticles (PEG-CuS NPs) with their peak absorption tuned to 1064 nm could be used both as a contrast agent for photoacoustic tomographic imaging of mouse tumor vasculature and as a mediator for confined photothermolysis of tumor cells in an orthotopic syngeneic 4T1 breast tumor model. PEG-CuS NPs showed stronger photoacoustic signal than hollow gold nanospheres and single-wall carbon nanotubes at 1064 nm. MicroPET imaging of 4T1 tumor-bearing mice showed a gradual accumulation of the NPs in the tumor over time. About 6.5% of injected dose were taken up in each gram of tumor tissue at 24 h after intravenous injection of 64Cu-labeled PEG-CuS NPs. For both photoacoustic imaging and therapeutic studies, nanosecond (ns)-pulsed laser was delivered with Q-switched Nd:YAG at a wavelength of 1064 nm. Unlike conventional photothermal ablation therapy mediated by continuous wave laser with which heat could spread to the surrounding normal tissue, interaction of CuS NPs with short pulsed laser deliver heat rapidly to the treatment volume keeping the thermal damage confined to the target tissues. Our data demonstrated that it is possible to use a single-compartment nanoplatform to achieve both photoacoustic tomography and highly selective tumor destruction at 1064 nm in small animals. Electronic supplementary information (ESI) available: Details on methods used for copper staining, synthesis of 64Cu-labeled PEG-CuS NPs, and PAT imaging equipment, and data summary on stability of PEG-CuS NPs, photographs of copper staining in tumor samples, temperature elevation comparing continues wave and pulsed laser beams, and quantitative analysis of treatment-induced necrosis of tumor tissues. See DOI: 10.1039/c4nr05386a

Graphene-wrapped sulfur particles as a rechargeable lithium-sulfur battery cathode material with high capacity and cycling stability.

PubMed

Wang, Hailiang; Yang, Yuan; Liang, Yongye; Robinson, Joshua Tucker; Li, Yanguang; Jackson, Ariel; Cui, Yi; Dai, Hongjie

2011-07-13

We report the synthesis of a graphene-sulfur composite material by wrapping poly(ethylene glycol) (PEG) coated submicrometer sulfur particles with mildly oxidized graphene oxide sheets decorated by carbon black nanoparticles. The PEG and graphene coating layers are important to accommodating volume expansion of the coated sulfur particles during discharge, trapping soluble polysulfide intermediates, and rendering the sulfur particles electrically conducting. The resulting graphene-sulfur composite showed high and stable specific capacities up to ∼600 mAh/g over more than 100 cycles, representing a promising cathode material for rechargeable lithium batteries with high energy density.

Improvement and evaluation of thermal, electrical, sealing and mechanical contacts, and their interface materials

NASA Astrophysics Data System (ADS)

Luo, Xiangcheng

Material contacts, including thermal, electrical, seating (fluid sealing and electromagnetic sealing) and mechanical (pressure) contacts, together with their interface materials, were, evaluated, and in some cases, improved beyond the state of the art. The evaluation involved the use of thermal, electrical and mechanical methods. For thermal contacts, this work evaluated and improved the heat transfer efficiency between two contacting components by developing various thermal interface pastes. Sodium silicate based thermal pastes (with boron nitride particles as the thermally conductive filler) as well as polyethylene glycol (PEG) based thermal pastes were developed and evaluated. The optimum volume fractions of BN in sodium silicate based pastes and PEG based pastes were 16% and 18% respectively. The contribution of Li+ ions to the thermal contact conductance in the PEG-based paste was confirmed. For electrical contacts, the relationship between the mechanical reliability and electrical reliability of solder/copper and silver-epoxy/copper joints was addressed. Mechanical pull-out testing was conducted on solder/copper and silver-epoxy/copper joints, while the contact electrical resistivity was measured. Cleansing of the copper surface was more effective for the reliability of silver-epoxy/copper joint than that of solder/copper joint. For sealing contacts, this work evaluated flexible graphite as an electromagnetic shielding gasket material. Flexible graphite was found to be at least comparable to conductive filled silicone (the state of the art) in terms of the shielding effectiveness. The conformability of flexible graphite with its mating metal surface under repeated compression was characterized by monitoring the contact electrical resistance, as the conformability is important to both electromagnetic scaling and fluid waling using flexible graphite. For mechanical contacts, this work focused on the correlation of the interface structure (such as elastic/plastic deformation, oxidation, strain hardening, passive layer damage, fracture, etc.) with the electrical contact resistance, which was measured in real time for contacts under dynamic compression, thus allowing both reversible and irreversible changes to be observed. The materials studied included metals (carbon steel, stainless steel, aluminum and copper), carbon fiber reinforced polymer-matrix composite (nylon-6), ceramic (mortar) and graphite, due to their relevance to fastening, concrete structures, electric brushes and electrical pressure contacts.

Optimal Solution Volume for Luminal Preservation: A Preclinical Study in Porcine Intestinal Preservation.

PubMed

Oltean, M; Papurica, M; Jiga, L; Hoinoiu, B; Glameanu, C; Bresler, A; Patrut, G; Grigorie, R; Ionac, M; Hellström, M

2016-03-01

Rodent studies suggest that luminal solutions alleviate the mucosal injury and prolong intestinal preservation but concerns exist that excessive volumes of luminal fluid may promote tissue edema. Differences in size, structure, and metabolism between rats and humans require studies in large animals before clinical use. Intestinal procurement was performed in 7 pigs. After perfusion with histidine-tryptophan-ketoglutarate (HTK), 40-cm-long segments were cut and filled with 13.5% polyethylene glycol (PEG) 3350 solution as follows: V0 (controls, none), V1 (0.5 mL/cm), V2 (1 mL/cm), V3 (1.5 mL/cm), and V4 (2 mL/cm). Tissue and luminal solutions were sampled after 8, 14, and 24 hours of cold storage (CS). Preservation injury (Chiu score), the apical membrane (ZO-1, brush-border maltase activity), and the electrolyte content in the luminal solution were studied. In control intestines, 8-hour CS in HTK solution resulted in minimal mucosal changes (grade 1) that progressed to significant subepithelial edema (grade 3) by 24 hours. During this time, a gradual loss in ZO-1 was recorded, whereas maltase activity remained unaltered. Moreover, variable degrees of submucosal edema were observed. Luminal introduction of high volumes (2 mL/mL) of PEG solution accelerated the development of the subepithelial edema and submucosal edema, leading to worse histology. However, ZO-1 was preserved better over time than in control intestines (no luminal solution). Maltase activity was reduced in intestines receiving luminal preservation. Luminal sodium content decreased in time and did not differ between groups. This PEG solution protects the apical membrane and the tight-junction proteins but may favor water absorption and tissue (submucosal) edema, and luminal volumes >2 mL/cm may result in worse intestinal morphology. Copyright © 2016 Elsevier Inc. All rights reserved.

Production of solid lipid submicron particles for protein delivery using a novel supercritical gas-assisted melting atomization process.

PubMed

Salmaso, Stefano; Elvassore, Nicola; Bertucco, Alberto; Caliceti, Paolo

2009-02-01

A supercritical carbon dioxide micronization technique based on gas-assisted melting atomization has been designed to prepare protein-loaded solid lipid submicron particles. The supercritical process was applied to homogeneous dispersions of insulin in lipid mixtures: (1) tristearin, Tween-80, phosphatidylcholine and 5 kDa PEG (1:0.1:0.9:1 and 1:0.1:0.9:2 weight ratio); and (2) tristearin, dioctyl sulfosuccinate and phosphatidylcholine (1:1:0.5 weight ratio). Optimized process conditions yielded dry nonagglomerated powders with high product recovery (70%, w/w). Dynamic light scattering and transmission electron microscopy showed that two size fractions of particles, with 80-120 and 200-400 nm diameters, were produced. In all final products, dimethylsulfoxide used to prepare the insulin/lipid mixture was below 20 ppm. Protein encapsulation efficiency increased up to 80% as the DMSO content in the insulin/lipid mixture increased. Compared to the particles without PEG, the polymer-containing particles dispersed rapidly in water, and the dispersions were more stable under centrifugation as less than 20% of suspended particles precipitated after extensive centrifugation. In vitro, the protein was slowly released from the formulation without PEG, while a burst and faster release were obtained from the formulations containing PEG. Subcutaneous injection to diabetic mice of insulin extracted from the particles showed that the supercritical process did not impair the protein hypoglycemic activity.

Dry-powder formulations of non-covalent protein complexes with linear or miktoarm copolymers for pulmonary delivery.

PubMed

Nieto-Orellana, Alejandro; Coghlan, David; Rothery, Malcolm; Falcone, Franco H; Bosquillon, Cynthia; Childerhouse, Nick; Mantovani, Giuseppe; Stolnik, Snow

2018-04-05

Pulmonary delivery of protein therapeutics has considerable clinical potential for treating both local and systemic diseases. However, poor protein conformational stability, immunogenicity and protein degradation by proteolytic enzymes in the lung are major challenges to overcome for the development of effective therapeutics. To address these, a family of structurally related copolymers comprising polyethylene glycol, mPEG 2k , and poly(glutamic acid) with linear A-B (mPEG 2k -lin-GA) and miktoarm A-B 3 (mPEG 2k -mik-(GA) 3 ) macromolecular architectures was investigated as potential protein stabilisers. These copolymers form non-covalent nanocomplexes with a model protein (lysozyme) which can be formulated into dry powders by spray-drying using common aerosol excipients (mannitol, trehalose and leucine). Powder formulations with excellent aerodynamic properties (fine particle fraction of up to 68%) were obtained with particle size (D 50 ) in the 2.5 µm range, low moisture content (<5%), and high glass transitions temperatures, i.e. formulation attributes all suitable for inhalation application. In aqueous medium, dry powders rapidly disintegrated into the original polymer-protein nanocomplexes which provided protection towards proteolytic degradation. Taken together, the present study shows that dry powders based on (mPEG 2k -polyGA)-protein nanocomplexes possess potentials as an inhalation delivery system. Copyright © 2018 Elsevier B.V. All rights reserved.

Interfacial Shear Strength and Adhesive Behavior of Silk Ionomer Surfaces.

PubMed

Kim, Sunghan; Geryak, Ren D; Zhang, Shuaidi; Ma, Ruilong; Calabrese, Rossella; Kaplan, David L; Tsukruk, Vladimir V

2017-09-11

The interfacial shear strength between different layers in multilayered structures of layer-by-layer (LbL) microcapsules is a crucial mechanical property to ensure their robustness. In this work, we investigated the interfacial shear strength of modified silk fibroin ionomers utilized in LbL shells, an ionic-cationic pair with complementary ionic pairing, (SF)-poly-l-glutamic acid (Glu) and SF-poly-l-lysine (Lys), and a complementary pair with partially screened Coulombic interactions due to the presence of poly(ethylene glycol) (PEG) segments and SF-Glu/SF-Lys[PEG] pair. Shearing and adhesive behavior between these silk ionomer surfaces in the swollen state were probed at different spatial scales and pressure ranges by using functionalized atomic force microscopy (AFM) tips as well as functionalized colloidal probes. The results show that both approaches were consistent in analyzing the interfacial shear strength of LbL silk ionomers at different spatial scales from a nanoscale to a fraction of a micron. Surprisingly, the interfacial shear strength between SF-Glu and SF-Lys[PEG] pair with partially screened ionic pairing was greater than the interfacial shear strength of the SF-Glu and SF-Lys pair with a high density of complementary ionic groups. The difference in interfacial shear strength and adhesive strength is suggested to be predominantly facilitated by the interlayer hydrogen bonding of complementary amino acids and overlap of highly swollen PEG segments.

Half doses of PEG-ES and senna vs. high-dose senna for bowel cleansing before colonoscopy: a randomized, investigator-blinded trial.

PubMed

Amato, Arnaldo; Radaelli, Franco; Paggi, Silvia; Terruzzi, Vittorio

2010-03-01

Patients' compliance with and tolerance of large-volume polyethylene glycol electrolyte solution (PEG-ES) have prompted continuous investigation with alternative forms of cleansing. High-dose senna is superior to PEG-ES for the quality of bowel cleansing, patient compliance, and tolerance, but its acceptance may be influenced by the incidence of abdominal pain. We hypothesized that a combination of half doses of PEG-ES and senna could minimize the incidence of abdominal pain without affecting the quality of bowel preparation. This randomized, investigator-blinded trial has been conducted on consecutive outpatients scheduled for elective colonoscopy at a single community-based hospital. Patients were randomly assigned to receive either 12 tablets of 12 mg senna and 2 l of PEG-ES (half-dose group, HDG) or 24 tablets of senna divided in two doses (senna group, SG) the day before colonoscopy. The main outcome measures were the quality of colon cleansing (Aronchick scoring scale) and the incidence of preparation-related abdominal pain. Secondary outcome measures were patients' compliance with the cleansing regimen, overall tolerability, prevalence of predefined side effects, and quality of right colon cleansing. A total of 296 patients were enrolled (HDG=151 and SG=145). Overall cleansing was excellent to good in 90.1 and 88.3% patients in HDG and SG, respectively (P=0.62). Preparation-related moderate-to-severe abdominal pain was reported by 6% patients in HDG and 15.2% in SG (P=0.009). No significant differences were observed for secondary outcomes. The regimen combining half doses of PEG-ES and senna provides high-quality bowel preparation and acceptable patient tolerance, with less abdominal pain compared with high-dose senna.

Chemoradionuclide Therapy with 186Re-Labeled Liposomal Doxorubicin: Toxicity, Dosimetry, and Therapeutic Response

PubMed Central

Soundararajan, Anuradha; Bao, Ande; Phillips, William T.; McManus, Linda M.

2011-01-01

Abstract This study was performed to determine the maximum tolerated dose (MTD) and therapeutic effects of rhenium-186 (186Re)-labeled liposomal doxorubicin (Doxil), investigate associated toxicities, and calculate radiation absorbed dose in head and neck tumor xenografts and normal organs. Doxil and control polyethylene glycol (PEG)-liposomes were labeled using 186Re-N,N-bis(2-mercaptoethyl)-N′,N′-diethylethylenediamine (BMEDA) method. Tumor-bearing rats received either no therapy (n=6), intravenous Doxil (n=4), or escalating radioactivity of 186Re-Doxil (185–925 MBq/kg) or 186Re-PEG-liposomes (1110–1665 MBq/kg) and were monitored for 28 days. Based on body weight loss and systemic toxicity, MTD for 186Re-Doxil and 186Re-PEG-liposomes were established at injected radioactivity/body weight of 740 and 1480 MBq/kg, respectively. 186Re-injected radioactivity/body weight for therapy studies was determined to be 555 MBq/kg for 186Re-Doxil and 1295 MBq/kg for 186Re-PEG-liposomes. All groups recovered from their body weight loss, leucopenia, and thrombocytopenia by 28 days postinjection. Normalized radiation absorbed dose to tumor was significantly higher for 186Re-Doxil (0.299±0.109 Gy/MBq) compared with 186Re-PEG-liposomes (0.096±0.120 Gy/MBq) (p<0.05). In a separate therapy study, tumor volumes were significantly smaller for 186Re-Doxil (555 MBq/kg) compared with 186Re-PEG-liposomes (1295 MBq/kg) (p<0.01) at 42 days postinjection. In conclusion, combination chemoradionuclide therapy with 186Re-Doxil has promising potential, because good tumor control was achieved with limited associated toxicity. PMID:21834653

A method for estimating dry forage intake by sheep using polyethylene glycol as a faecal marker measured with NIRS.

PubMed

Hassoun, P; Viudes, G; Autran, P; Bastianelli, D; Bocquier, F

2013-08-01

In experiments based on ruminants' individual dry matter intake (DMI) assessment, several external markers can be used to estimate faecal output when total faeces collection is not possible. However, preparation of the markers to be administered and analytical procedures used for marker content determination are time-consuming thus strongly limiting the number of animals involved in the experiments. In this paper, polyethylene glycol (PEG, molecular weight 6000 da) was tested as a faecal marker. Four trials were conducted on dry, non-lactating ewes kept in digestibility crates that allowed individual measurements. The overall experiment was designed to assess the major factors that could lessen the effectiveness of this method, assuming that the use of grab samples of faeces is sufficient. Trial 1 was designed to test two levels of PEG (20 and 40 g/day) administered in two equal amounts. Trial 2 was designed to test the effect of either a single morning (0800 h) dose (20 g/day) or a twice daily administration (0800 and 1600 h) of the same fractionated dose. Trial 3 was designed to test a 20 g/day dose of PEG administered once daily to ewes fed with hays of different qualities: medium (MH) and low (LH). In trial 4, a lower dose of PEG (10 g/day) was administered once a day to ewes fed with fresh oat-vetch forage. It was demonstrated that PEG could be precisely estimated (average prediction error = 3.47 g/kg) with near-infrared reflectance spectroscopy (NIRS). On the basis of the four trials, it has been proved that PEG administration (20 and 40 g/day) did not significantly affect the DMI of ewes fed dry diets (trials 1, 2 and 3), whereas there was an unexpected increase of DMI for ewes fed exclusively with green feed (trial 4) without DM digestibility modification. Providing PEG as a single dose (0800 h) or split into two equal parts (0800 and 1600 h) did not alter the estimated DMI. Considering the interest of grab sampling, there were clear variations of PEG in faeces with higher concentrations observed at 0800 and 1600 h and lower concentrations at 1400 h. Consequently, with PEG (measured with NIRS) administered once and using the grab sampling procedure (morning collection), it is possible to estimate the DMI of dry feeds with good accuracy. For green feeds, more research is needed as the estimated results are still highly variable.

Synthesis and characterization of novel dual-responsive nanogels and their application as drug delivery systems

NASA Astrophysics Data System (ADS)

Peng, Jinrong; Qi, Tingting; Liao, Jinfeng; Fan, Min; Luo, Feng; Li, He; Qian, Zhiyong

2012-03-01

In this study, a temperature/pH dual-response nanogel based on NIPAm, MAA, and PEGMA was synthesized via emulsion polymerization and characterized by 1H-NMR, FT-IR, TEM and DLS. By introducing a novel initiator, through which PEG-AIBN-PEG was synthesized, it was revealed that the PEG segments from PEG-AIBN-PEG with a dosage of initiator had a significant influence over the macro-state and stability of the nanogels. In order to optimize the feeding prescription for better application as a drug delivery system, the effect of the co-monomer contents on the response to stimuli (temperature and pH value) and cytotoxicity of the nanogels has been studied in detail. The results demonstrated that the responsiveness, reversibility and volume phase transition critical value of the nanogels could be controlled by adjusting the feeding ratio of the co-monomers in the synthesis process. MTT assay results revealed that nanogels with appropriate compositions showed good biocompatibility and relatively low toxicity. Most importantly, by studying the drug loading behavior, it was found that the dimensions of the drug molecules had a considerable influence on the drug loading efficiency and loading capacity of the nanogels, and that the mechanism by which drug molecule sizes influence the drug loading behavior of nanogels needs further investigation. The results indicated that such PNMP nanogels might have potential applications in drug delivery and other medical applications, but that the drug loading mechanism must be further developed.

Sol-gel approach for fabrication of coated anodized titanium wire for solid-phase microextraction: highly efficient adsorbents for enrichment of trace polar analytes.

PubMed

Jia, Jing; Xu, Lili; Wang, Shuai; Wang, Licheng; Liu, Xia

2014-05-01

Nanotubular titania film was prepared in situ on titanium wire and was used as the fiber substrate for solid-phase microextraction (SPME) because of its high surface-to-volume ratio, easy preparation, and mechanical stability. Three different functional coatings, β-cyclodextrin (β-CD), β-cyclodextrin-co-poly(ethylenepropylene glycol) (β-CD/PEG), and polyethylene glycol (PEG)-based sorbents were chemically bonded to the nanostructured wire surface via sol-gel technology to further enhance the absorbing capability and extraction selectivity. Coupled to gas chromatography-flame ionic detection (GC-FID), the prepared SPME fibers were investigated using diverse compounds. The results indicated that the fibers showed good mechanical strength, excellent thermal stability, and wonderful capacity and selectivity to polar compounds, including polar aromatic compounds, alcohols, and ketones. Combining the superior hydrophilic property of a bonded functional molecule and the highly porous structure of a fiber coating, the prepared PEG-coated SPME fiber showed much higher adsorption affinity to ephedrine and methylephedrine than β-CD and β-CD/PEG fibers. The as-established PEG-coated SPME-GC analytical method provided excellent sensitivity (LODs, 0.004 and 0.001 ng mL(-1) for ephedrine and methylephedrine, respectively) and better linear range (0.01-2 000 μg L(-1)). In addition, it has surprising repeatability and reproducibility. Finally, the present approach was used to analyze ephedrine and methylephedrine from real urine samples, and reliable results were obtained.

Inhibition of Microtubule Depolymerization by Osmolytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bachand, George D.; Jain, Rishi; Ko, Randy

Microtubule dynamics play a critical role in the normal physiology of eukaryotic cells as well as a number of cancers and neurodegenerative disorders. The polymerization/depolymerization of microtubules is regulated by a variety of stabilizing and destabilizing factors, including microtubule-associated proteins and therapeutic agents (e.g., paclitaxel, nocodazole). Here in this paper, we describe the ability of the osmolytes polyethylene glycol (PEG) and trimethylamine-N-oxide (TMAO) to inhibit the depolymerization of individual microtubule filaments for extended periods of time (up to 30 days). We further show that PEG stabilizes microtubules against both temperature- and calcium-induced depolymerization. Our results collectively suggest that the observedmore » inhibition may be related to combination of the kosmotropic behavior and excluded volume/osmotic pressure effects associated with PEG and TMAO. Lastly, taken together with prior studies, our data suggest that the physiochemical properties of the local environment can regulate microtubule depolymerization and may potentially play an important role in in vivo microtubule dynamics.« less

Inhibition of Microtubule Depolymerization by Osmolytes

DOE PAGES

Bachand, George D.; Jain, Rishi; Ko, Randy; ...

2018-04-24

Microtubule dynamics play a critical role in the normal physiology of eukaryotic cells as well as a number of cancers and neurodegenerative disorders. The polymerization/depolymerization of microtubules is regulated by a variety of stabilizing and destabilizing factors, including microtubule-associated proteins and therapeutic agents (e.g., paclitaxel, nocodazole). Here in this paper, we describe the ability of the osmolytes polyethylene glycol (PEG) and trimethylamine-N-oxide (TMAO) to inhibit the depolymerization of individual microtubule filaments for extended periods of time (up to 30 days). We further show that PEG stabilizes microtubules against both temperature- and calcium-induced depolymerization. Our results collectively suggest that the observedmore » inhibition may be related to combination of the kosmotropic behavior and excluded volume/osmotic pressure effects associated with PEG and TMAO. Lastly, taken together with prior studies, our data suggest that the physiochemical properties of the local environment can regulate microtubule depolymerization and may potentially play an important role in in vivo microtubule dynamics.« less

Impaired acid neutralization in the duodenum in pancreatic insufficiency.

PubMed

Dutta, S K; Russell, R M; Iber, F L

1979-10-01

The influence of severe exocrine pancreatic disease on the acid-neutralizing capacity of the duodenum was studied in five patients with pancreatic insufficiency (PI) and six control subjects using duodenal perfusion-marker technique. Hydrochloric acid (0.1 N containing 1% PEG) was infused at constant rates (1.2, 4.5 and 7.0 ml/min) into the duodenum just distal to the duodenal bulb. Samples were aspirated from the tip of the duodenal perfusion tube located at the ligament of Treitz. All samples were analyzed for volume, pH, titrable acidity, PEG and [14C]PEG (gastric marker) determination. Patients with PI demonstrated significantly diminished ability to neutralize various acid loads as compared to controls who virtually completely neutralized acid loads in the range of maximal gastric acid secretion. Exogenous secretin did not significantly improve percent acid neutralized in PI. These data clearly indicate that patients with PI have significantly impaired ability to neutralize even small loads of acid in the duodenum.

Polyethylene Glycol Camouflaged Earthworm Hemoglobin.

PubMed

Jani, Vivek P; Jelvani, Alborz; Moges, Selamawit; Nacharaju, Parimala; Roche, Camille; Dantsker, David; Palmer, Andre; Friedman, Joel M; Cabrales, Pedro

2017-01-01

Nearly 21 million components of blood and whole blood and transfused annually in the United States, while on average only 13.6 million units of blood are donated. As the demand for Red Blood Cells (RBCs) continues to increase due to the aging population, this deficit will be more significant. Despite decades of research to develop hemoglobin (Hb) based oxygen (O2) carriers (HBOCs) as RBC substitutes, there are no products approved for clinical use. Lumbricus terrestris erythrocruorin (LtEc) is the large acellular O2 carrying protein complex found in the earthworm Lumbricus terrestris. LtEc is an extremely stable protein complex, resistant to autoxidation, and capable of transporting O2 to tissue when transfused into mammals. These characteristics render LtEc a promising candidate for the development of the next generation HBOCs. LtEc has a short half-life in circulation, limiting its application as a bridge over days, until blood became available. Conjugation with polyethylene glycol (PEG-LtEc) can extend LtEc circulation time. This study explores PEG-LtEc pharmacokinetics and pharmacodynamics. To study PEG-LtEc pharmacokinetics, hamsters instrumented with the dorsal window chamber were subjected to a 40% exchange transfusion with 10 g/dL PEG-LtEc or LtEc and followed for 48 hours. To study the vascular response of PEG-LtEc, hamsters instrumented with the dorsal window chamber received multiple infusions of 10 g/dL PEG-LtEc or LtEc solution to increase plasma LtEc concentration to 0.5, then 1.0, and 1.5 g/dL, while monitoring the animals' systemic and microcirculatory parameters. Results confirm that PEGylation of LtEc increases its circulation time, extending the half-life to 70 hours, 4 times longer than that of unPEGylated LtEc. However, PEGylation increased the rate of LtEc oxidation in vivo. Vascular analysis verified that PEG-LtEc showed the absence of microvascular vasoconstriction or systemic hypertension. The molecular size of PEG-LtEc did not change the colloid osmotic pressure or blood volume expansion capacity compared to LtEc, due to LtEc's already large molecular size. Taken together, these results further encourage the development of PEG-LtEc as an O2 carrying therapeutic.

Surface phase behavior and microstructure of lipid/PEG-emulsifier monolayer-coated microbubbles.

PubMed

Borden, Mark A; Pu, Gang; Runner, Gabriel J; Longo, Marjorie L

2004-06-01

Langmuir trough methods and fluorescence microscopy were combined to investigate the phase behavior and microstructure of monolayer shells coating micron-scale bubbles (microbubbles) typically used in biomedical applications. The monolayer shell consisted of a homologous series of saturated acyl chain phospholipids and an emulsifier containing a single hydrophobic stearate chain and polyethylene glycol (PEG) head group. PEG-emulsifier was fully miscible with expanded phase lipids and phase separated from condensed phase lipids. Phase coexistence was observed in the form of dark condensed phase lipid domains surrounded by a sea of bright, emulsifier-rich expanded phase. A rich assortment of condensed phase area fractions and domain morphologies, including networks and other novel structures, were observed in each batch of microbubbles. Network domains were reproduced in Langmuir monolayers under conditions of heating-cooling followed by compression-expansion, as well as in microbubble shells that underwent surface flow with slight compression. Domain size decreased with increased cooling rate through the phase transition temperature, and domain branching increased with lipid acyl chain length at high cooling rates. Squeeze-out of the emulsifier at a surface pressure near 35 mN/m was indicated by a plateau in Langmuir isotherms and directly visualized with fluorescence microscopy, although collapse of the solid lipid domains occurred at much higher surface pressures. Compression of the monolayer past the PEG-emulsifier squeeze-out surface pressure resulted in a dark shell composed entirely of lipid. Under certain conditions, the PEG-emulsifier was reincorporated upon subsequent expansion. Factors that affect shell formation and evolution, as well as implications for the rational design of microbubbles in medical applications, are discussed.

Determination of the mechanical properties of solid and cellular polymeric dosage forms by diametral compression.

PubMed

Blaesi, Aron H; Saka, Nannaji

2016-07-25

At present, the immediate-release solid dosage forms, such as the oral tablets and capsules, are granular solids. They release drug rapidly and have adequate mechanical properties, but their manufacture is fraught with difficulties inherent in processing particulate matter. Such difficulties, however, could be overcome by liquid-based processing. Therefore, we have recently introduced polymeric cellular (i.e., highly porous) dosage forms prepared from a melt process. Experiments have shown that upon immersion in a dissolution medium, the cellular dosage forms with polyethylene glycol (PEG) as excipient and with predominantly open-cell topology disintegrate by exfoliation, thus enabling rapid drug release. If the volume fraction of voids of the open-cell structures is too large, however, their mechanical strength is adversely affected. At present, the common method for determining the tensile strength of brittle, solid dosage forms (such as select granular forms) is the diametral compression test. In this study, the theory of diametral compression is first refined to demonstrate that the relevant mechanical properties of ductile and cellular solids (i.e., the elastic modulus and the yield strength) can also be extracted from this test. Diametral compression experiments are then conducted on PEG-based solid and cellular dosage forms. It is found that the elastic modulus and yield strength of the open-cell structures are about an order of magnitude smaller than those of the non-porous solids, but still are substantially greater than the stiffness and strength requirements for handling the dosage forms manually. This work thus demonstrates that melt-processed polymeric cellular dosage forms that release drug rapidly can be designed and manufactured to have adequate mechanical properties. Copyright © 2016. Published by Elsevier B.V.

Accuracy of cancellous bone volume fraction measured by micro-CT scanning.

PubMed

Ding, M; Odgaard, A; Hvid, I

1999-03-01

Volume fraction, the single most important parameter in describing trabecular microstructure, can easily be calculated from three-dimensional reconstructions of micro-CT images. This study sought to quantify the accuracy of this measurement. One hundred and sixty human cancellous bone specimens which covered a large range of volume fraction (9.8-39.8%) were produced. The specimens were micro-CT scanned, and the volume fraction based on Archimedes' principle was determined as a reference. After scanning, all micro-CT data were segmented using individual thresholds determined by the scanner supplied algorithm (method I). A significant deviation of volume fraction from method I was found: both the y-intercept and the slope of the regression line were significantly different from those of the Archimedes-based volume fraction (p < 0.001). New individual thresholds were determined based on a calibration of volume fraction to the Archimedes-based volume fractions (method II). The mean thresholds of the two methods were applied to segment 20 randomly selected specimens. The results showed that volume fraction using the mean threshold of method I was underestimated by 4% (p = 0.001), whereas the mean threshold of method II yielded accurate values. The precision of the measurement was excellent. Our data show that care must be taken when applying thresholds in generating 3-D data, and that a fixed threshold may be used to obtain reliable volume fraction data. This fixed threshold may be determined from the Archimedes-based volume fraction of a subgroup of specimens. The threshold may vary between different materials, and so it should be determined whenever a study series is performed.

Unique regulatory properties of the UDP-glucose:. beta. -1,4-glucan synthetase of Acetobacter xylinum. [Acetobacter xylinum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benziman, M.; Aloni, Y.; Delmer, D.P.

1983-01-01

Conditions have been found for an extremely efficient transfer of glucose from UDP-glucose to a cellulosic ..beta..-1,4-glucan product, using enzyme preparations derived from cells of Acetobacter xylinum. Membrane fractions obtained by rupturing cells in the presence of 20% (w/v) polyethylene glycol-4000 (PEG-4000) exhibited UDP-glucose:..beta..-1,4-glucan synthetase activity 3- to 10-fold higher than those previously reported. Enzyme prepared in this fashion also shows a further marked activation by GTP. The activation (apparent K/sub alpha/ = 35 ..mu..M) is quite specific for GTP. A variety of other nucleotides and nucleotide derivatives had no effect on activity. Guanosine-5'-(lambda-thio)triphosphate, an analog of GTP, is evenmore » more efficient than GTP (K/sub alpha/ = 17 ..mu..M). Enzyme prepared in the absence of PEG-4000 does not respond to GTP because it lacks a protein factor essential for GTP activation. PEG-4000 promotes the interaction of the protein factor with the enzyme. The factor itself is devoid of synthetase activity and does not stimulate activity of the enzyme in the absence of GTP. Under optimal conditions, in the presence of GTP, factor, and PEG-4000, initial rates of enzyme activity that are 200 times higher than those previously reported can be achieved. Such rates exceed 40% of the in vivo rate of cellulose synthesis from glucose. 26 references, 3 figures, 3 tables.« less

Interactions between carbamazepine and polyethylene glycol (PEG) 6000: characterisations of the physical, solid dispersed and eutectic mixtures.

PubMed

Naima, Z; Siro, T; Juan-Manuel, G D; Chantal, C; René, C; Jerome, D

2001-02-01

The influence of a hydrophilic carrier (PEG 6000) on the polymorphism of carbamazepine, an antiepileptic drug, was investigated in binary physical mixtures and solid dispersions by means of differential scanning calorimetry (DSC), thermal gravimetry, hot-stage microscopy (HSM), and X-ray diffractometry, respectively. This study provides also an attempt to develop a method to calculate more precisely the eutectic composition. In rather ideal physical mixtures, carbamazepine was found as monoclinic Form III. In solid dispersions, the drug was found to crystallize as trigonal Form II; a eutectic invariant in the PEG 6000-rich composition domain (6% of carbamazepine mass) was evidenced by DSC experiments and confirmed by HSM observations. In the binary phase diagram the ideal carbamazepine liquidus curve was located at temperatures higher than the respective experimental ones. This suggests that drug can be maintained in the liquid state in the temperature-mass fraction (T--x) region between the two carbamazepine liquidus curves. This indicates in turn that attractive interactions occur between carbamazepine and PEG 6000-chains. These interactions have been also claimed to prevent carbamazepine from degradation into iminostilbene (a compound resulting from the chemical degradation of carbamazepine which is postulated to be responsible for the idiosyncratic toxicity of the drug) and thought to lead to the crystallization of metastable Carbamazepine II from melt. The negative excess entropy for eutectic mixtures indicated that the drug crystals are finely dispersed in the bulk of polymer chains.

Effect of cold drawing ratio on γ′ precipitation in Inconel X-750

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ha, Jeong Won; Research and Development Center, KOS Limited, Yangsan 626-230; Seong, Baek Seok

2014-10-15

Inconel X-750 is a Ni-based precipitation-hardened superalloy having large tensile and fracture strengths. In the study, X-750 wires were cold drawn to different extents. Small angle neutron scattering was employed to quantitatively measure the size and volume fraction of the γ′ phase as a function of the cold drawing ratio (DR) and aging temperature. The presence and size of γ′ precipitates were confirmed by transmission electron microscopy. The drawing ratio had an important effect on the volume fraction of the γ′ precipitates. However, the size of the precipitates was independent on the drawing ratio. The specimen with the minimum drawingmore » ratio (DR0) produced the largest volume fraction of γ′ as compared with large drawing ratio (DR) specimens such as DR17 and DR42. The small volume fraction of the γ′ phase for a sizeable drawing ratio was associated with the large amount of nucleation sites for secondary carbides, M{sub 23}C{sub 6}, and the fast diffusion path, i.e., dislocation, needed to form M{sub 23}C{sub 6}. A Cr depletion zone around the secondary carbides raised the solubility of γ′. Therefore, the significant drawing ratio contributing to the large volume fraction of the secondary carbides decreased the volume fraction of the γ′ precipitates in Inconel X-750. - Highlights: • The volume fraction of secondary carbides increased with the drawing ratio. • The volume fraction of γ′ decreased as the drawing ratio increased. • The drawing ratio affected the γ′ volume fraction with no variation of the γ' size. • The volume fraction of γ′ was affected by the secondary carbide volume fraction.« less

Development of nanoparticle applications in cell imaging, bioassay and reactive oxygen species detection based on surface-enhanced raman spectroscopy

NASA Astrophysics Data System (ADS)

Huang, Yiming

Surface-enhanced Raman scattering (SERS) has been developed over forty years with a wide variety of applications. Signals enhanced from single molecule absorbed on the surface of metallic nanoparticles can be up to 14-order-of-magnitude. This is due to the resonance between the optical field and surface plasmon of the metal substrate. Nanoshells have been chosen as substrates since they do not need to pre-aggregate due to their tunable optical property. We developed Raman imaging system by incorporating functionalized nanoshells, cells and SERS. Nanoshells have been coated with different self-assembled monolayers containing poly(ethylene glycol) (PEG) molecules. Probes have been designed by coating nanoshells with Raman active PEG molecules and delivered into macrophage cells. The imaging technique requires less preparation and provides the information of nanoshells in semi-quantitative way in vitro. We developed half-sandwich bioassay by detecting low volume of antigens on nitrocellulose membrane, detected by SERS. Antibodies were grafted to the surface of nanoshells and were conjugated to the antigens on the nitrocellulose membrane for detection. Raman active PEGs were conjugated onto the metal substrate for recognition and quantification. The benefits of this assay are that it is faster, easier to execute and requires less volume of antigen to conjugate onto the substrate. We also developed reactive oxygen species (ROS) sensors by incubating PEGs and either 4-nitrobenzenethiol (4-NBT) or 4-mercaptophenol (4-MP) on the surface of nanoshells. By analyzing the changes of SERS spectrum, the production of hydroxyl radicals produced in the Fenton reaction can be tracked in low concentrations. The sensors were designed to track ROS production within cells when they are under oxidative stress. The methods developed in this thesis are versatile, and can be broadly applied to the study of different subtracts, such as gold colloid.

Development and characterization of hyaluronic acid decorated PLGA nanoparticles for delivery of 5-fluorouracil.

PubMed

Yadav, Awesh K; Agarwal, Abhinav; Rai, Gopal; Mishra, Pradeep; Jain, Sanyog; Mishra, Anil K; Agrawal, Himanshu; Agrawal, Govind P

2010-11-01

The present investigation was aimed to develop and explore the prospective of engineered PLGA nanoparticles as vehicles for targeted delivery of 5-fluorouracil (5-FU). Nanoparticles of 5-FU-loaded hyaluronic acid-poly(ethylene glycol)-poly(lactide-co-glycolide) (HA-PEG-PLGA-FU) copolymer were prepared and characterized by FTIR, NMR, transmission electron microscopy, particle size analysis, DSC, and X-ray diffractometer measurement studies. The nanoparticulate formulation was evaluated for in vitro release, hemolytic toxicity, and hematological toxicity. Cytotoxicity studies were performed on Ehrlich ascites tumor (EAT) cell lines using MTT cell proliferation assay. Biodistribution studies of 99m Tc labeled formulation were conducted on EAT-bearing mice. The in vivo tumor inhibition study was also performed after i.v. administration of HA-PEG-PLGA-FU nanoparticles. The HA conjugated formulation was found to be less hemolytic but more cytotoxic as compared to free drug. The hematological data suggested that HA-PEG-PLGA-FU formulation was less immunogenic compared to plain drug. The tissue distribution studies displayed that HA-PEG-PLGA-FU were able to deliver a higher concentration of 5-FU in the tumor mass. In addition, the HA-PEG-PLGA-FU nanoparticles reduced tumor volume significantly in comparison with 5-FU. Thus, it was concluded that the conjugation of HA imparts targetability to the formulation, and enhanced permeation and retention effect ruled out its access to the non-tumor tissues, at the same time favored selective entry in tumors, thereby reducing the side-effects both in vitro and in vivo.

Thermal and ultrasonic evaluation of porosity in composite laminates

NASA Technical Reports Server (NTRS)

Johnston, Patrick H.; Winfree, William P.; Long, Edward R., Jr.; Kullerd, Susan M.; Nathan, N.; Partos, Richard D.

1992-01-01

The effects of porosity on damage incurred by low-velocity impact are investigated. Specimens of graphite/epoxy composite were fabricated with various volume fractions of voids. The void fraction was independently determined using optical examination and acid resin digestion methods. Thermal diffusivity and ultrasonic attenuation were measured, and these results were related to the void volume fraction. The relationship between diffusivity and fiber volume fraction was also considered. The slope of the ultrasonic attenuation coefficient was found to increase linearly with void content, and the diffusivity decreased linearly with void volume fraction, after compensation for an approximately linear dependence on the fiber volume fraction.

Benefits from additives and xylanase during enzymatic hydrolysis of bamboo shoot and mature bamboo.

PubMed

Li, Kena; Wang, Xiao; Wang, Jingfeng; Zhang, Junhua

2015-09-01

Effects of additives (BSA, PEG 6000, and Tween 80) on enzymatic hydrolysis of bamboo shoot and mature bamboo fractions (bamboo green, bamboo timber, bamboo yellow, bamboo node, and bamboo branches) by cellulases and/or xylanase were evaluated. The addition of additives was comparable to the increase of cellulase loadings in the conversion of cellulose and xylan in bamboo fractions. Supplementation of xylanase (1 mg/g DM) with cellulases (10 FPU/g DM) in the hydrolysis of bamboo fractions was more efficient than addition of additives in the production of glucose and xylose. Moreover, addition of additives could further increase the glucose release from different bamboo fractions by cellulases and xylanase. Bamboo green exhibited the lowest hydrolyzability. Almost all of the polysaccharides in pretreated bamboo shoot fractions were hydrolyzed by cellulases with the addition of additives or xylanase. Additives and xylanase showed great potential for reducing cellulase requirement in the hydrolysis of bamboo. Copyright © 2015 Elsevier Ltd. All rights reserved.

A numerical study of the phase behaviors of drug particle/star triblock copolymer mixtures in dilute solutions for drug carrier application

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Shanhui; Tong, Chaohui; Zhu, Yuejin, E-mail: zhuyuejin@nbu.edu.cn

The complex microstructures of drug particle/ABA star triblock copolymer in dilute solutions have been investigated by a theoretical approach which combines the self-consistent field theory and the hybrid particle-field theory. Simulation results reveal that, when the volume fraction of drug particles is smaller than the saturation concentration, the drug particle encapsulation efficiency is 100%, and micelle loading capacity increases with increasing particle volume fraction. When the volume fraction of drug particles is equal to the saturation concentration, the micelles attain the biggest size, and micelle loading capacity reaches a maximum value which is independent of the copolymer volume fraction. Whenmore » the volume fraction of drug particles is more than the saturation concentration, drug particle encapsulation efficiency decreases with increasing volume fraction of drug particles. Furthermore, it is found that the saturation concentration scales linearly with the copolymer volume fraction. The above simulation results are in good agreement with experimental results.« less

Low Volume Resuscitation with Cell Impermeants

DTIC Science & Technology

2013-10-01

LVR solution produced the best individual protection. Mixtures of trehalose, raffinose, gluconate, and sorbitol at a specific ratio was optimal. This... Sorbitol  Gluconate  Trehalose  Raffinose These agents have been extensively used in organ preservation solutions so their safety and...10% 5% Sorbitol Na-Gluconate Trehalose Na-Lactobionate Raffinose PEG-8K 122 98

Protozoa inhibition by different salts: Osmotic stress or ionic stress?

PubMed

Li, Changhao; Li, Jingya; Lan, Christopher Q; Liao, Dankui

2017-09-01

Cell density and morphology changes were tested to examine the effects of salts including NaHCO 3 , NaCl, KHCO 3 , and KCl at 160 mM on protozoa. It was demonstrated that ionic stress rather than osmotic stress led to protozoa cell death and NaHCO 3 was shown to be the most effective inhibitor. Deformation of cells and cell shrinkage were observed when protozoan cells were exposed to polyethylene glycol (PEG) or any of the salts. However, while PEG treated cells could fully recover in both number and size, only a small portion of the salt-treated cells survive and cell size was 36-58% smaller than the regular. The disappearance of salt-treated protozoa cells was hypothetically attributed to disruption of the cytoplasmic membrane of these cells. It is further hypothesized that the PEG-treated protozoan cells carried out regulatory volume increase (RVI) after the osmotic shock but the RVI of salt-treated protozoa was hurdled to varied extents. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1418-1424, 2017. © 2017 American Institute of Chemical Engineers.

Electrical, thermal and structural properties of plasticized waste cooking oil-based polyurethane solid polymer electrolyte

NASA Astrophysics Data System (ADS)

Huzaizi, Rahmatina Mohd; Tahir, Syuhada Mohd; Mahbor, Kamisah Mohamad

2017-12-01

Waste cooking oil-based polyol was synthesized using epoxidation and hydroxylation methods. The polyol was combined with 4,4-diphenylmethane diisocyanate to produce polyurethane (PU) to be used as polymer host in solid polymer electrolyte. 30 wt% LiClO4 was added as doping salt and two types of plasticizers were used; ethylene carbonate (PU-EC) and polyethylene glycol (PU-PEG). The SPE films were characterized using Fourier transform infrared spectroscopy, electrochemical impedance spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The highest conductivity achieved was 8.4 x 10-8 S cm-1 upon addition of 10 wt% EC. The XRD results showed a decrease of crystalline peaks in PU-EC and the increase in PU-PEG. DSC results revealed that the films; PU, PU-EC and PU-PEG had glass transition temperatures of 159.7, 106.0 and 179.7 °C, respectively. The results showed that the addition of EC increased the amorphous region and the free volume in the SPE structure, thus resulted in higher ionic conductivity.

Penetration of theophylline and adenosine into excised human skin from binary and ternary vehicles: effect of a nonionic surfactant.

PubMed

Kadir, R; Stempler, D; Liron, Z; Cohen, S

1989-02-01

A nonionic surfactant, diethyleneglycol lauryl ether (PEG-2-L), increases the flux of either theophylline or adenosine by a factor of 2.2-2.7, when these are delivered from propionic acid solutions into human skin samples, with respect to propionic acid alone. At the same time, the flux of propionic acid from the same vehicles is decreased. Significant expansion of the partial molal volumes vi of both purines occurs following incorporation of PEG-2-L into their propionic acid solution. Hence, the enhancing effect of this surfactant arises mainly from an increase in the excess free energy of these solutes in the donor phase ("push" effect). Paraffin oil increases the flux of either drug from propionic acid by an entirely different mechanism. It enhances the flux of propionic acid into the skin, thus promoting the partitioning of the purine solute in the modified skin barrier ("pull" effect). Indeed, the magnitude of vi of either purine in propionic acid:paraffin oil solution gives no indication of a significant interaction between paraffin oil and the purine solute. Finally, the penetration enhancing effects of PEG-2-L and paraffin oil combined together in the same propionic acid vehicle are additive, resulting in a flux which is approximately the sum total of fluxes obtained separately with PEG-2-L or paraffin oil.

Organic Chemical Characterization and Mass Balance of a Hydraulically Fractured Well: From Fracturing Fluid to Produced Water over 405 Days.

PubMed

Rosenblum, James; Thurman, E Michael; Ferrer, Imma; Aiken, George; Linden, Karl G

2017-12-05

A long-term field study (405 days) of a hydraulically fractured well from the Niobrara Formation in the Denver-Julesburg Basin was completed. Characterization of organic chemicals used in hydraulic fracturing and their changes through time, from the preinjected fracturing fluid to the produced water, was conducted. The characterization consisted of a mass balance by dissolved organic carbon (DOC), volatile organic analysis by gas chromatography/mass spectrometry, and nonvolatile organic analysis by liquid chromatography/mass spectrometry. DOC decreased from 1500 mg/L in initial flowback to 200 mg/L in the final produced water. Only ∼11% of the injected DOC returned by the end of the study, with this 11% representing a maximum fraction returned since the formation itself contributes DOC. Furthermore, the majority of returning DOC was of the hydrophilic fraction (60-85%). Volatile organic compound analysis revealed substantial concentrations of individual BTEX compounds (0.1-11 mg/L) over the 405-day study. Nonvolatile organic compounds identified were polyethylene glycols (PEGs), polypropylene glycols (PPG), linear alkyl-ethoxylates, and triisopropanolamine (TIPA). The distribution of PEGs, PPGs, and TIPA and their ubiquitous presence in our samples and the literature illustrate their potential as organic tracers for treatment operations or in the event of an environmental spill.

Effective protein extraction protocol for proteomics studies of Jerusalem artichoke leaves.

PubMed

Zhang, Meide; Shen, Shihua

2013-07-01

Protein extraction is a crucial step for proteomics studies. To establish an effective protein extraction protocol suitable for two-dimensional electrophoresis (2DE) analysis in Jerusalem artichoke (Helianthus tuberosus L.), three different protein extraction methods-trichloroacetic acid/acetone, Mg/NP-40, and phenol/ammonium acetate-were evaluated using Jerusalem artichoke leaves as source materials. Of the three methods, trichloroacetic acid/acetone yielded the best protein separation pattern and highest number of protein spots in 2DE analysis. Proteins highly abundant in leaves, such as Rubisco, are typically problematic during leaf 2DE analysis, however, and this disadvantage was evident using trichloroacetic acid/acetone. To reduce the influence of abundant proteins on the detection of low-abundance proteins, we optimized the trichloroacetic acid/acetone method by incorporating a PEG fractionation approach. After optimization, 363 additional (36.2%) protein spots were detected on the 2DE gel. Our results suggest that trichloroacetic acid/acetone method is a better protein extraction technique than Mg/NP-40 and phenol/ammonium acetate in Jerusalem artichoke leaf 2DE analysis, and that trichloroacetic acid/acetone method combined with PEG fractionation procedure is the most effective approach for leaf 2DE analysis of Jerusalem artichoke. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Organic chemical characterization and mass balance of a hydraulically fractured well: From fracturing fluid to produced water over 405 days

USGS Publications Warehouse

Rosenblum, James; Thurman, E. Michael; Ferrer, Imma; Aiken, George R.; Linden, Karl G.

2017-01-01

A long-term field study (405 days) of a hydraulically fractured well from the Niobrara Formation in the Denver-Julesburg Basin was completed. Characterization of organic chemicals used in hydraulic fracturing and their changes through time, from the preinjected fracturing fluid to the produced water, was conducted. The characterization consisted of a mass balance by dissolved organic carbon (DOC), volatile organic analysis by gas chromatography/mass spectrometry, and nonvolatile organic analysis by liquid chromatography/mass spectrometry. DOC decreased from 1500 mg/L in initial flowback to 200 mg/L in the final produced water. Only ∼11% of the injected DOC returned by the end of the study, with this 11% representing a maximum fraction returned since the formation itself contributes DOC. Furthermore, the majority of returning DOC was of the hydrophilic fraction (60–85%). Volatile organic compound analysis revealed substantial concentrations of individual BTEX compounds (0.1–11 mg/L) over the 405-day study. Nonvolatile organic compounds identified were polyethylene glycols (PEGs), polypropylene glycols (PPG), linear alkyl-ethoxylates, and triisopropanolamine (TIPA). The distribution of PEGs, PPGs, and TIPA and their ubiquitous presence in our samples and the literature illustrate their potential as organic tracers for treatment operations or in the event of an environmental spill.

The capability of radial basis function to forecast the volume fractions of the annular three-phase flow of gas-oil-water.

PubMed

Roshani, G H; Karami, A; Salehizadeh, A; Nazemi, E

2017-11-01

The problem of how to precisely measure the volume fractions of oil-gas-water mixtures in a pipeline remains as one of the main challenges in the petroleum industry. This paper reports the capability of Radial Basis Function (RBF) in forecasting the volume fractions in a gas-oil-water multiphase system. Indeed, in the present research, the volume fractions in the annular three-phase flow are measured based on a dual energy metering system including the 152 Eu and 137 Cs and one NaI detector, and then modeled by a RBF model. Since the summation of volume fractions are constant (equal to 100%), therefore it is enough for the RBF model to forecast only two volume fractions. In this investigation, three RBF models are employed. The first model is used to forecast the oil and water volume fractions. The next one is utilized to forecast the water and gas volume fractions, and the last one to forecast the gas and oil volume fractions. In the next stage, the numerical data obtained from MCNP-X code must be introduced to the RBF models. Then, the average errors of these three models are calculated and compared. The model which has the least error is picked up as the best predictive model. Based on the results, the best RBF model, forecasts the oil and water volume fractions with the mean relative error of less than 0.5%, which indicates that the RBF model introduced in this study ensures an effective enough mechanism to forecast the results. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Effects of Size, Shape, and Surface Functional Group of Gold Nanostructures on Their Adsorption and Internalization by Cells

PubMed Central

Cho, Eun Chul; Au, Leslie; Zhang, Qiang; Xia, Younan

2010-01-01

In this study, we examined the effects of size, shape, and surface chemistry of gold nanostructures on their uptake (including both adsorption and internalization) by SK-BR-3 breast cancer cells. We used both spherical and cubic Au nanostructures (nanospheres and nanocages, respectively) of two different sizes, and their surface was modified with poly(ethylene glycol) (PEG), antibody anti-HER2, or poly(allyamine hydrochloride) (PAA). Our results showed that the size of the Au nanostructures influenced their uptake by the cells in a similar way regardless of the surface chemistry, while the shape dependency could vary depending on the surface functional group. In addition, the cells preferred to take up the Au nanostructures covered by different surface groups in the following order: PAA>> anti-HER2> PEG. The fraction of Au nanostructures attached to the cell surface was also dependent on the aforementioned parameters. PMID:20029850

Quantitative tomographic measurements of opaque multiphase flows

DOE Office of Scientific and Technical Information (OSTI.GOV)

GEORGE,DARIN L.; TORCZYNSKI,JOHN R.; SHOLLENBERGER,KIM ANN

2000-03-01

An electrical-impedance tomography (EIT) system has been developed for quantitative measurements of radial phase distribution profiles in two-phase and three-phase vertical column flows. The EIT system is described along with the computer algorithm used for reconstructing phase volume fraction profiles. EIT measurements were validated by comparison with a gamma-densitometry tomography (GDT) system. The EIT system was used to accurately measure average solid volume fractions up to 0.05 in solid-liquid flows, and radial gas volume fraction profiles in gas-liquid flows with gas volume fractions up to 0.15. In both flows, average phase volume fractions and radial volume fraction profiles from GDTmore » and EIT were in good agreement. A minor modification to the formula used to relate conductivity data to phase volume fractions was found to improve agreement between the methods. GDT and EIT were then applied together to simultaneously measure the solid, liquid, and gas radial distributions within several vertical three-phase flows. For average solid volume fractions up to 0.30, the gas distribution for each gas flow rate was approximately independent of the amount of solids in the column. Measurements made with this EIT system demonstrate that EIT may be used successfully for noninvasive, quantitative measurements of dispersed multiphase flows.« less

Volume Fraction Determination in Cast Superalloys and DS Eutectic Alloys by a New Practice for Manual Point Counting

NASA Technical Reports Server (NTRS)

Andrews, C. W.

1976-01-01

Volume fraction of a constituent or phase was estimated in six specimens of conventional and DS-eutectic superalloys, using ASTM E562-76, a new standard recommended practice for determining volume fraction by systematic manual point count. Volume fractions determined ranged from 0.086 to 0.36, and with one exception, the 95 percent relative confidence limits were approximately 10 percent of the determined volume fractions. Since the confidence-limit goal of 10 percent, which had been arbitrarily chosen previously, was achieved in all but one case, this application of the new practice was considered successful.

Tutorial for Collecting and Processing Images of Composite Structures to Determine the Fiber Volume Fraction

NASA Technical Reports Server (NTRS)

Conklin, Lindsey

2017-01-01

Fiber-reinforced composite structures have become more common in aerospace components due to their light weight and structural efficiency. In general, the strength and stiffness of a composite structure are directly related to the fiber volume fraction, which is defined as the fraction of fiber volume to total volume of the composite. The most common method to measure the fiber volume fraction is acid digestion, which is a useful method when the total weight of the composite, the fiber weight, and the total weight can easily be obtained. However, acid digestion is a destructive test, so the material will no longer be available for additional characterization. Acid digestion can also be difficult to machine out specific components of a composite structure with complex geometries. These disadvantages of acid digestion led the author to develop a method to calculate the fiber volume fraction. The developed method uses optical microscopy to calculate the fiber area fraction based on images of the cross section of the composite. The fiber area fraction and fiber volume fraction are understood to be the same, based on the assumption that the shape and size of the fibers are consistent in the depth of the composite. This tutorial explains the developed method for optically determining fiber area fraction performed at NASA Langley Research Center.

The effect of the processing and formulation parameters on the size of nanoparticles based on block copolymers of poly(ethylene glycol) and poly(N-isopropylacrylamide) with and without hydrolytically sensitive groups.

PubMed

Neradovic, D; Soga, O; Van Nostrum, C F; Hennink, W E

2004-05-01

Block copolymers of poly(ethylene glycol) (PEG) as a hydrophilic block and N-isopropylacrylamide (PNIPAAm) or poly (NIPAAm-co-N-(2-hydroxypropyl) methacrylamide-dilactate) (poly(NIPAAm-co-HPMAm-dilactate)) as a thermosensitive block, are able to self-assemble in water into nanoparticles above the cloud point (CP) of the thermosensitive block. The influence of processing and the formulation parameters on the size of the nanoparticles was studied using dynamic light scattering. PNIPAAm-b-PEG 2000 polymers were not suitable for the formation of small and stable particles. Block copolymers with PEG 5000 and 10000 formed relatively small and stable particles in aqueous solutions at temperatures above the CP of the thermosensitive block. Their size decreased with increasing molecular weight of the thermosensitive block, decreasing polymer concentration and using water instead of phosphate buffered saline as solvent. Extrusion and ultrasonication were inefficient methods to size down the polymeric nanoparticles. The heating rate of the polymer solutions was a dominant factor for the size of the nanoparticles. When an aqueous polymer solution was slowly heated through the CP, rather large particles (> or = 200 nm) were formed. Regardless the polymer composition, small nanoparticles (50-70 nm) with a narrow size distribution were formed, when a small volume of an aqueous polymer solution below the CP was added to a large volume of heated water. In this way the thermosensitive block copolymers rapidly pass their CP ('heat shock' procedure), resulting in small and stable nanoparticles.

A macromolecular crowding study of RNA folding and activity: polymer pore size matters! (Conference Presentation)

NASA Astrophysics Data System (ADS)

Börner, Richard; Fiorini, Erica; Paudel, Bishnu; Rueda, David; Sigel, Roland K. O.

2016-03-01

Catalytic RNAs, like the group IIB intron ribozyme of S. cerevesiae, require a high magnesium(II) concentration to show folding and function in vitro [1]. In contrast, in vivo conditions are characterized by a highly crowded cellular environment and much lower ion concentration. Molecular crowding agents are a widespread tool to mimic cellular crowding [2]. However, particular physical/chemical properties explaining the crowders influence are mostly not understood. In this study, we gain new insights on how polymer properties like viscosity, pore size etc. influence the activity and folding of a large RNA. We combined bulk activity assays and single-molecule Förster Resonance Energy Transfer experiments, screening the PEG volume fraction (%) and molecular weight (MW). Our results revealed that upon the influence of crowding agents, a compaction of the underlying structure depends on the PEG % and the presence of different PEG MW and % unveiled an optimal pore size in terms of catalytic activity. In summary, an increasing density of the crowding environment shifts the RNA towards the most compact state, but the ribozyme is only active if the crowders network matches its size [4]. We interpret the most compact state as necessary, but not sufficient, to keep the ribozyme active. Financial support from the European Research Council (MIRNA N° 259092, to RKOS), the Swiss National Fund (SNF), and the Forschungskredit Grant of the University of Zürich (FK-14-096 and 15-092 to RB) are gratefully acknowledged. [1] Swisher J.F., Su L.J., Brenowitz M., Anderson V.E., Pyle A.M., J. Mol. Bio., 315, 297-310 (2002). [2] Kilburn D., Roh J.H., Guo L., Briber R.M., Woodson S.A., JACS, 132, 8690-6 (2010). [3] Steiner M., Karunatilaka K.S., Sigel R.K.O., Rueda D., Proc. Natl. Acad. Sci. U.S.A.,105, 13853-8 (2008). [4] aBörner R, Fiorini E, Sigel R.K.O., Chimia, 69, 207-212 (2015).; bFiorini E., Paudel B., Börner R., Rueda D., Sigel R.K.O., submitted. [5] König S.L.B., Hadzic M., Fiorini E., Börner R., Kowerko D., Blanckenhorn W.U., Sigel R.K.O., PLoS ONE, 8, e84157 (2013).

Effects of Polymer Hydrophobicity on Protein Structure and Aggregation Kinetics in Crowded Milieu.

PubMed

Breydo, Leonid; Sales, Amanda E; Frege, Telma; Howell, Mark C; Zaslavsky, Boris Y; Uversky, Vladimir N

2015-05-19

We examined the effects of water-soluble polymers of various degrees of hydrophobicity on the folding and aggregation of proteins. The polymers we chose were polyethylene glycol (PEG) and UCON (1:1 copolymer of ethylene glycol and propylene glycol). The presence of additional methyl groups in UCON makes it more hydrophobic than PEG. Our earlier analysis revealed that similarly sized PEG and UCON produced different changes in the solvent properties of water in their solutions and induced morphologically different α-synuclein aggregates [Ferreira, L. A., et al. (2015) Role of solvent properties of aqueous media in macromolecular crowding effects. J. Biomol. Struct. Dyn., in press]. To improve our understanding of molecular mechanisms defining behavior of proteins in a crowded environment, we tested the effects of these polymers on secondary and tertiary structure and aromatic residue solvent accessibility of 10 proteins [five folded proteins, two hybrid proteins; i.e., protein containing ordered and disordered domains, and three intrinsically disordered proteins (IDPs)] and on the aggregation kinetics of insulin and α-synuclein. We found that effects of both polymers on secondary and tertiary structures of folded and hybrid proteins were rather limited with slight unfolding observed in some cases. Solvent accessibility of aromatic residues was significantly increased for the majority of the studied proteins in the presence of UCON but not PEG. PEG also accelerated the aggregation of protein into amyloid fibrils, whereas UCON promoted aggregation to amyloid oligomers instead. These results indicate that even a relatively small change in polymer structure leads to a significant change in the effect of this polymer on protein folding and aggregation. This is an indication that protein folding and especially aggregation are highly sensitive to the presence of other macromolecules, and an excluded volume effect is insufficient to describe their effect.

A Mixed Micelle Formulation for Oral Delivery of Vitamin K.

PubMed

Sun, Feilong; Jaspers, Tessa C C; van Hasselt, Peter M; Hennink, Wim E; van Nostrum, Cornelus F

2016-09-01

To develop a stable micellar formulation of vitamin K for oral delivery, because the commercial and clinically used formulation of vitamin K (Konakion® MM) destabilizes at gastric pH resulting in low bioavailability of this vitamin in neonates with cholestasis. Mixed micelles composed of EPC, DSPE-PEG 2000 and glycocholic acid, with and without vitamin K, were prepared by a film hydration method. The influence of pH on the stability of the micelles was analyzed by dynamic light scattering (DLS). The critical micelle concentration (CMC) was determined by fluorescence spectroscopy using pyrene and the morphology was evaluated by transmission electron microscopy . Caco-2 cells were used to study the cytocompatibilty. Mixed micelles with mean diameters from 7.1 to 11.0 nm and a narrow size distribution (PDI < 0.2) were obtained after 3 membrane extrusion cycles. Konakion® MM formed aggregated particles at gastric pH, which was avoided through steric stabilization by introducing PEG. TEM showed that mixed micelles had a spherical size (diameter of around 10 nm) with a narrow size distribution in agreement with the DLS results. The loading capacities for vitamin K of mixed micelles with varying molar fractions of DSPE-PEG and EPC (from 0/100 to 50/50 (mol/mol)) were 10.8-5.0 w%, respectively. The mixed micelles showed good cytocompatibility at concentrations of glycocholic acid between 0.12 and 1.20 mM. Mixed micelles with superior stability to Konakion® MM at low pH were obtained by introducing DSPE-PEG 2000. These are therefore attractive oral formulations for vitamin K.

Diffusion tensor spectroscopic imaging of the human brain in children and adults.

PubMed

Fotso, Kevin; Dager, Stephen R; Landow, Alec; Ackley, Elena; Myers, Orrin; Dixon, Mindy; Shaw, Dennis; Corrigan, Neva M; Posse, Stefan

2017-10-01

We developed diffusion tensor spectroscopic imaging (DTSI), based on proton-echo-planar-spectroscopic imaging (PEPSI), and evaluated the feasibility of mapping brain metabolite diffusion in adults and children. PRESS prelocalized DTSI at 3 Tesla (T) was performed using navigator-based correction of movement-related phase errors and cardiac gating with compensation for repetition time (TR) related variability in T 1 saturation. Mean diffusivity (MD) and fractional anisotropy (FA) of total N-acetyl-aspartate (tNAA), total creatine (tCr), and total choline (tCho) were measured in eight adults (17-60 years) and 10 children (3-24 months) using b max  = 1734 s/mm 2 , 1 cc and 4.5 cc voxel sizes, with nominal scan times of 17 min and 8:24 min. Residual movement-related phase encoding ghosting (PEG) was used as a regressor across scans to correct overestimation of MD. After correction for PEG, metabolite slice-averaged MD estimated at 20% PEG were lower (P < 0.042) for adults (0.17/0.20/0.18 × 10 -3 mm 2 /s) than for children (0.26/0.27/0.24 × 10 -3 mm 2 /s). Extrapolated to 0% PEG, the MD estimates decreased further (0.09/0.11/0.11 × 10 -3 mm 2 /s versus 0.15/0.16/0.15 × 10 -3 mm 2 /s). Slice-averaged FA of tNAA (P = 0.049), tCr (P = 0.067), and tCho (P = 0.003) were higher in children. This high-speed DTSI approach with PEG regression allows for estimation of metabolite MD and FA with improved tolerance to movement. Our preliminary data suggesting age-related changes support DTSI as a sensitive technique for investigating intracellular markers of biological processes. Magn Reson Med 78:1246-1256, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Intensified fractionation of brewery yeast waste for the recovery of invertase using aqueous two-phase systems.

PubMed

De León-González, Grecia; González-Valdez, José; Mayolo-Deloisa, Karla; Rito-Palomares, Marco

2016-11-01

The potential recovery of high-value products from brewery yeast waste confers value to this industrial residue. Aqueous two-phase systems (ATPS) have demonstrated to be an attractive alternative for the primary recovery of biological products and are therefore suitable for the recovery of invertase from this residue. Sixteen different polyethylene glycol (PEG)-potassium phosphate ATPS were tested to evaluate the effects of PEG molecular weight (MW) and tie-line length (TLL) upon the partition behavior of invertase. Concentrations of crude extract from brewery yeast waste were then varied in the systems that presented the best behaviors to intensify the potential recovery of the enzyme. Results show that the use of a PEG MW 400 g mol -1 system with a TLL of 45.0% (w/w) resulted in an invertase bottom phase recovery with a purification factor of 29.5 and a recovery yield of up to 66.2% after scaling the system to a total weight of 15.0 g. This represents 15.1 mg of invertase per mL of processed bottom phase. With these results, a single-stage ATPS process for the recovery of invertase is proposed. © 2015 International Union of Biochemistry and Molecular Biology, Inc.

Insight into interfacial effect on effective physical properties of fibrous materials. I. The volume fraction of soft interfaces around anisotropic fibers.

PubMed

Xu, Wenxiang; Wang, Han; Niu, Yanze; Bai, Jingtao

2016-01-07

With advances in interfacial properties characterization technologies, the interfacial volume fraction is a feasible parameter for evaluating effective physical properties of materials. However, there is a need to determine the interfacial volume fraction around anisotropic fibers and a need to assess the influence of such the interfacial property on effective properties of fibrous materials. Either ways, the accurate prediction of interfacial volume fraction is required. Towards this end, we put forward both theoretical and numerical schemes to determine the interfacial volume fraction in fibrous materials, which are considered as a three-phase composite structure consisting of matrix, anisotropic hard spherocylinder fibers, and soft interfacial layers with a constant dimension coated on the surface of each fiber. The interfacial volume fraction actually represents the fraction of space not occupied by all hard fibers and matrix. The theoretical scheme that adopts statistical geometry and stereological theories is essentially an analytic continuation from spherical inclusions. By simulating such three-phase chopped fibrous materials, we numerically derive the interfacial volume fraction. The theoretical and numerical schemes provide a quantitative insight that the interfacial volume fraction depends strongly on the fiber geometries like fiber shape, geometric size factor, and fiber size distribution. As a critical interfacial property, the present contribution can be further drawn into assessing effective physical properties of fibrous materials, which will be demonstrated in another paper (Part II) of this series.

Discrete nanoparticles induce loss of Legionella pneumophila biofilms from surfaces.

PubMed

Raftery, Tara D; Kerscher, Petra; Hart, Ashley E; Saville, Steven L; Qi, Bin; Kitchens, Christopher L; Mefford, Olin Thompson; McNealy, Tamara L

2014-08-01

Nanoparticles (NPs) have been shown to induce dispersal events in microbial biofilms but the mechanism of the dispersal is unknown. Biofilms contaminate many man-made aquatic systems such as cooling towers, spas and dental lines. Within these biofilms, Legionella pneumophila is a primary pathogen, leading to these environments serving as sources for disease outbreaks. Here we show a reduction in biofilm bio-volume upon treatment with citrate-coated 6-nm platinum NPs, polyethylene glycol (PEG)-coated 11-nm gold NPs, and PEG-coated 8-nm iron oxide NPs. Treatment with citrate-coated 8-nm silver NPs, however, did not reduce biomass. The synthesis of NPs that remain dispersed and resist irreversible aggregation in the exposure media appears to be a key factor in the ability of NPs to induce biofilm dispersal.

Mesoporous Akaganeite of Adjustable Pore Size Synthesized using Mixed Templates

NASA Astrophysics Data System (ADS)

Zhang, Y.; Ge, D. L.; Ren, H. P.; Fan, Y. J.; Wu, L. M.; Sun, Z. X.

2017-12-01

Mesoporous akaganeite with large and adjustable pore size was synthesized through a co-template method, which was achieved by the combined interaction between PEG2000 and alkyl amines with different lengths of the straight carbon chain. The characterized results indicate that the synthesized samples show comparatively narrow BJH pore size distributions and centered at 14.3 nm when PEG and HEPA was used, and it could be enlarged to 16.8 and 19.4 nm respectively through changing the alkyl amines to DDA and HDA. Meanwhile, all the synthesized akaganeite possess relativity high specific surface area ranging from 183 to 281 m2/g and high total pore volume of 0.98 to 1.5 cm3/g. A possible mechanism leading to the pore size changing was also proposed.

Secretion modification region-derived peptide blocks exosome release and mediates cell cycle arrest in breast cancer cells.

PubMed

Huang, Ming-Bo; Gonzalez, Ruben R; Lillard, James; Bond, Vincent C

2017-02-14

Discovery and development of a novel anticancer PEG-SMR-Clu peptide to prevent breast cancer metastasis. How breast cancer cells and primary mammary epithelial cells interact and communicate with each other to promote tumorigenesis and how to prevent tumor metastasis has long been a concern of researchers. Cancer cells secrete exosomes containing proteins and RNA. These factors can influence tumor development by directly targeting cancer cells and tumor stroma. In this study, we determined the effects of a peptide as an inhibitor of exosome secretion on breast tumors. We developed a peptide derived from the Secretion Modification Region (SMR) of HIV-1 Nef protein that was modified with PEG on the N-terminus and with a Clusterin (Clu)-binding peptide on the C-terminus. Attachment of PEG to the SMR peptide, termed PEGylation, offers improved water solubility and stability as well as reduced clearance through the kidneys, leading to a longer circulation time. The 12-mer Clu-binding peptide plays multiple roles in tumor development and metastasis. The Clu peptide can be detected by antibody in vivo, thus it has the potential to be used to monitor tumor status and treatment efficacy in animal studies and eventually in cancer patients. PEG-SMRwt-Clu and PEG-SMRwt peptides inhibited the growth of both of MCF-7 (estrogen responsive, ER+) and MDA-MD-231 (estrogen non-responsive, ER-) human breast cancer cells in a dose and time-dependent manner, without inducing cytotoxic effects. The SMRwt peptide, combined with paclitaxel, induced G2/M phase cell cycle arrest on MCF-7 and MDA-MB-231 cells but did not promote apoptosis. PEG-SMRwt-Clu peptide treatment blocked exosome release from both MCF-7 and MDA-MB-231 cells. This effect was blocked by knockdown of the chaperone protein mortalin by either antibody or siRNA. MCF-7 and MDA-MB-231 breast tumor cells were treated with PEG-SMR-Clu peptide alone and in combination with paclitaxel and cisplatin. Cell proliferation and viabilty were determined via cell cycle analysis using Cellometer imaging cytometry, Annexin V and MTT assays. The effects of the PEG-SMR-Clu peptide on tumor exosome release were determined by testing isolated exosome fractions, for (i) expression of CD63 and Alix proteins by Western blotting, (ii) NanoSight nanoparticle tracking analysis (NTA 10) to measure exosomes size and concentration, and (iii) measurement of acetylcholinesterase (AchE) for exosome specific enzyme activity. PEG-SMRwt-CLU peptides inhibited the growth of human breast cancer cells and blocked tumor exosome release in vitro. The peptide alone did not cause increased cytotoxicity or apoptosis induction, but did cause cell cycle G2/M phase arrest in both estrogen responsive and non-responsive breast cancer cells. These data suggest a potential therapeutic value of SMR to prevent breast cancer metastasis and as an adjuvant for the chemotherapeutic treatment of human breast cancer.

The optimal fiber volume fraction and fiber-matrix property compatibility in fiber reinforced composites

NASA Technical Reports Server (NTRS)

Pan, Ning

1992-01-01

Although the question of minimum or critical fiber volume fraction beyond which a composite can then be strengthened due to addition of fibers has been dealt with by several investigators for both continuous and short fiber composites, a study of maximum or optimal fiber volume fraction at which the composite reaches its highest strength has not been reported yet. The present analysis has investigated this issue for short fiber case based on the well-known shear lag (the elastic stress transfer) theory as the first step. Using the relationships obtained, the minimum spacing between fibers is determined upon which the maximum fiber volume fraction can be calculated, depending on the fiber packing forms within the composites. The effects on the value of this maximum fiber volume fraction due to such factors as fiber and matrix properties, fiber aspect ratio and fiber packing forms are discussed. Furthermore, combined with the previous analysis on the minimum fiber volume fraction, this maximum fiber volume fraction can be used to examine the property compatibility of fiber and matrix in forming a composite. This is deemed to be useful for composite design. Finally some examples are provided to illustrate the results.

SU-E-T-427: Cell Surviving Fractions Derived From Tumor-Volume Variation During Radiotherapy for Non-Small Cell Lung Cancer: Comparison with Predictive Assays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chvetsov, A; Schwartz, J; Mayr, N

2014-06-01

Purpose: To show that a distribution of cell surviving fractions S{sub 2} in a heterogeneous group of patients can be derived from tumor-volume variation curves during radiotherapy for non-small cell lung cancer. Methods: Our analysis was based on two data sets of tumor-volume variation curves for heterogeneous groups of 17 patients treated for nonsmall cell lung cancer with conventional dose fractionation. The data sets were obtained previously at two independent institutions by using megavoltage (MV) computed tomography (CT). Statistical distributions of cell surviving fractions S{sup 2} and cell clearance half-lives of lethally damaged cells T1/2 have been reconstructed in eachmore » patient group by using a version of the two-level cell population tumor response model and a simulated annealing algorithm. The reconstructed statistical distributions of the cell surviving fractions have been compared to the distributions measured using predictive assays in vitro. Results: Non-small cell lung cancer presents certain difficulties for modeling surviving fractions using tumor-volume variation curves because of relatively large fractional hypoxic volume, low gradient of tumor-volume response, and possible uncertainties due to breathing motion. Despite these difficulties, cell surviving fractions S{sub 2} for non-small cell lung cancer derived from tumor-volume variation measured at different institutions have similar probability density functions (PDFs) with mean values of 0.30 and 0.43 and standard deviations of 0.13 and 0.18, respectively. The PDFs for cell surviving fractions S{sup 2} reconstructed from tumor volume variation agree with the PDF measured in vitro. Comparison of the reconstructed cell surviving fractions with patient survival data shows that the patient survival time decreases as the cell surviving fraction increases. Conclusion: The data obtained in this work suggests that the cell surviving fractions S{sub 2} can be reconstructed from the tumor volume variation curves measured during radiotherapy with conventional fractionation. The proposed method can be used for treatment evaluation and adaptation.« less

Effect of PEG-PDLLA polymeric nanovesicles loaded with doxorubicin and hematoporphyrin monomethyl ether on human hepatocellular carcinoma HepG2 cells in vitro.

PubMed

Xiang, Guang-Hua; Hong, Guo-Bin; Wang, Yong; Cheng, Du; Zhou, Jing-Xing; Shuai, Xin-Tao

2013-01-01

To evaluate the cytotoxicity of poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-PDLLA) nanovesicles loaded with doxorubicin (DOX) and the photosensitizer hematoporphyrin monomethyl ether (HMME) on human hepatocellular carcinoma HepG2 cells and to investigate potential apoptotic mechanisms. PEG-PDLLA nanovesicles were simultaneously loaded with DOX and HMME (PEG-PDLLA-DOX-HMME), and PEG-PDLLA nanovesicles were loaded with DOX (PEG-PDLLA-DOX), HMME (PEG-PDLLA-HMME), or the PEG-PDLLA nanovesicle alone as controls. The cytotoxicity of PEG-PDLLA-DOX-HMME, PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA against HepG2 cells was measured, and the cellular reactive oxygen species, percentage of cells with mitochondrial membrane potential depolarization, and apoptotic rate following treatment were determined. Four nanovesicles (PEG-PDLLA-DOX-HMME, PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA) were synthesized, and mean particle sizes were 175±18 nm, 154±3 nm, 196±2 nm, and 147±15 nm, respectively. PEG-PDLLA-DOX-HMME was more cytotoxic than PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA. PEG-PDLLA-HMME-treated cells had the highest mean fluorescence intensity, followed by PEG-PDLLA-DOX-HMME-treated cells, whereas PEG-PDLLA-DOX- and PEG-PDLLA-treated cells had a similar fluorescence intensity. Mitochondrial membrane potential depolarization was observed in 54.2%, 59.4%, 13.8%, and 14.8% of the cells treated with PEG-PDLLA-DOX-HMME, PEG-PDLLA-HMME, PEG-PDLLA-DOX, and PEG-PDLLA, respectively. The apoptotic rate was significantly higher in PEG-PDLLA-DOX-HMME-treated cells compared with PEG-PDLLA-DOX- and PEG-PDLLA-HMME-treated cells. The PEG-PDLLA nanovesicle, a drug delivery carrier, can be simultaneously loaded with two anticancer drugs (hydrophilic DOX and hydrophobic HMME). PEG-PDLLA-DOX-HMME cytotoxicity to HepG2 cells is significantly higher than the PEG-PDLLA nanovesicle loaded with DOX or HMME alone, and DOX and HMME have a synergistic effect against human hepatocellular carcinoma HepG2 cells.

The effect of particle volume fraction and temperature on the enhancement of thermal conductivity of maghemite (γ-Fe2O3) water-based nanofluids

NASA Astrophysics Data System (ADS)

Nurdin, Irwan; Satriananda

2017-03-01

Thermal conductivity of maghemite nanofluids were experimentally investigated at different maghemite nanoparticles volume fraction and temperatures. Maghemite nanofluids were prepared by suspending maghemite nanoparticles in water as base fluids. The thermal conductivity ratio of maghemite nanofluids was linearly increase with increasing particle volume fraction and temperature. The highest enhancement of thermal conductivity is 42.5% which is obtained at particle volume fraction 2.5% and temperature 60 °C.

Phase-field simulations of coherent precipitate morphologies and coarsening kinetics

NASA Astrophysics Data System (ADS)

Vaithyanathan, Venugopalan

2002-09-01

The primary aim of this research is to enhance the fundamental understanding of coherent precipitation reactions in advanced metallic alloys. The emphasis is on a particular class of precipitation reactions which result in ordered intermetallic precipitates embedded in a disordered matrix. These precipitation reactions underlie the development of high-temperature Ni-base superalloys and ultra-light aluminum alloys. Phase-field approach, which has emerged as the method of choice for modeling microstructure evolution, is employed for this research with the focus on factors that control the precipitate morphologies and coarsening kinetics, such as precipitate volume fractions and lattice mismatch between precipitates and matrix. Two types of alloy systems are considered. The first involves L1 2 ordered precipitates in a disordered cubic matrix, in an attempt to model the gamma' precipitates in Ni-base superalloys and delta' precipitates in Al-Li alloys. The effect of volume fraction on coarsening kinetics of gamma' precipitates was investigated using two-dimensional (2D) computer simulations. With increase in volume fraction, larger fractions of precipitates were found to have smaller aspect ratios in the late stages of coarsening, and the precipitate size distributions became wider and more positively skewed. The most interesting result was associated with the effect of volume fraction on the coarsening rate constant. Coarsening rate constant as a function of volume fraction extracted from the cubic growth law of average half-edge length was found to exhibit three distinct regimes: anomalous behavior or decreasing rate constant with volume fraction at small volume fractions ( ≲ 20%), volume fraction independent or constant behavior for intermediate volume fractions (˜20--50%), and the normal behavior or increasing rate constant with volume fraction for large volume fractions ( ≳ 50%). The second alloy system considered was Al-Cu with the focus on understanding precipitation of metastable tetragonal theta'-Al 2Cu in a cubic Al solid solution matrix. In collaboration with Chris Wolverton at Ford Motor Company, a multiscale model, which involves a novel combination of first-principles atomistic calculations with a mesoscale phase-field microstructure model, was developed. Reliable energetics in the form of bulk free energy, interfacial energy and parameters for calculating the elastic energy were obtained using accurate first-principles calculations. (Abstract shortened by UMI.)

Analysis of White Matter Damage in Patients with Multiple Sclerosis via a Novel In Vivo MR Method for Measuring Myelin, Axons, and G-Ratio.

PubMed

Hagiwara, A; Hori, M; Yokoyama, K; Nakazawa, M; Ueda, R; Horita, M; Andica, C; Abe, O; Aoki, S

2017-10-01

Myelin and axon volume fractions can now be estimated via MR imaging in vivo, as can the g-ratio, which equals the ratio of the inner to the outer diameter of a nerve fiber. The purpose of this study was to evaluate WM damage in patients with MS via this novel MR imaging technique. Twenty patients with relapsing-remitting MS with a combined total of 149 chronic plaques were analyzed. Myelin volume fraction was calculated based on simultaneous tissue relaxometry. Intracellular and CSF compartment volume fractions were quantified via neurite orientation dispersion and density imaging. Axon volume fraction and g-ratio were calculated by combining these measurements. Myelin and axon volume fractions and g-ratio were measured in plaques, periplaque WM, and normal-appearing WM. All metrics differed significantly across the 3 groups ( P < .001, except P = .027 for g-ratio between periplaque WM and normal-appearing WM). Those in plaques differed most from those in normal-appearing WM. The percentage changes in plaque and periplaque WM metrics relative to normal-appearing WM were significantly larger in absolute value for myelin volume fraction than for axon volume fraction and g-ratio ( P < .001, except P = .033 in periplaque WM relative to normal-appearing WM for comparison between myelin and axon volume fraction). In this in vivo MR imaging study, the myelin of WM was more damaged than axons in plaques and periplaque WM of patients with MS. Myelin and axon volume fractions and g-ratio may potentially be useful for evaluating WM damage in patients with MS. © 2017 by American Journal of Neuroradiology.

A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with transferrin and tamoxifen for treating brain gliomas.

PubMed

Li, Yan; He, Hai; Jia, Xinru; Lu, Wan-Liang; Lou, Jinning; Wei, Yen

2012-05-01

A pH-sensitive dual-targeting drug carrier (G4-DOX-PEG-Tf-TAM) was synthesized with transferrin (Tf) conjugated on the exterior and Tamoxifen (TAM) in the interior of the fourth generation PAMAM dendrimers for enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. It was found that, on average, 7 doxorubicine (DOX) molecules, over 30 PEG(1000) and PEG(2000) chains and one Tf group were bonded on the periphery of each G4 PAMAM dendrimer, while 29 TAM molecules were encapsulated into the interior of per dendrimer. The pH-triggered DOX release was 32% at pH 4.5 and 6% at pH 7.4, indicating a comparatively fast drug release at weak acidic condition and stable state of the carrier at physiological environment. The in vitro assay of the drug transport across the BBB model showed that G4-DOX-PEG-Tf-TAM exhibited higher BBB transportation ability with the transporting ratio of 6.06% in 3 h. The carrier was internalized into C6 glioma cells upon crossing the BBB model by the coactions of TfR-mediated endocytosis and the inhibition effect of TAM to the drug efflux transports. Moreover, it also displayed the in vitro accumulation of DOX in the avascular C6 glioma spheroids made the tumor volume effectively reduced. Copyright © 2012 Elsevier Ltd. All rights reserved.

Liquid Superlubricity of Polyethylene Glycol Aqueous Solution Achieved with Boric Acid Additive.

PubMed

Ge, Xiangyu; Li, Jinjin; Zhang, Chenhui; Luo, Jianbin

2018-03-27

Boric acid is a weak acid and has been used as a lubrication additive because of its special structure. In this study, we report that boric acid could achieve a robust superlubricity (μ < 0.01) as an additive in polyethylene glycol (PEG) aqueous solution at the Si 3 N 4 /SiO 2 interfaces. The superlow and steady friction coefficient of approximately 0.004-0.006 could be achieved with boric acid under neutral conditions (pH of approximately 6.4), which is different from the acidic conditions leading to superlubricity. The influence of various factors, including boric acid concentration, sliding speed, applied load, PEG molecular weight, and the volume of lubricant on the superlubricity, were investigated. The results reveal that the PEG aqueous solution with the boric acid additive could achieve superlubricity under a wide range of conditions. The surface composition analysis shows that the synergy effect between boric acid and PEG provides sufficient H + ions to realize the running-in process. Moreover, a composite tribochemical film composed of silica and ammonia-containing compounds were formed on the ball surface, contributing to the superlubricity. The film thickness calculation shows that superlubricity was achieved in a mixed lubrication region, and therefore, the superlubricity state was dominated by both the composite tribochemical film formed via the tribochemical reaction on the contact surfaces and the hydrodynamic lubricating film between the contact surfaces. Such a liquid superlubricity achieved under neutral conditions is of importance for both scientific understanding and engineering applications.

Role of the Methoxy Group in Immune Responses to mPEG-Protein Conjugates

PubMed Central

2012-01-01

Anti-PEG antibodies have been reported to mediate the accelerated clearance of PEG-conjugated proteins and liposomes, all of which contain methoxyPEG (mPEG). The goal of this research was to assess the role of the methoxy group in the immune responses to mPEG conjugates and the potential advantages of replacing mPEG with hydroxyPEG (HO-PEG). Rabbits were immunized with mPEG, HO-PEG, or t-butoxyPEG (t-BuO-PEG) conjugates of human serum albumin, human interferon-α, or porcine uricase as adjuvant emulsions. Assay plates for enzyme-linked immunosorbent assays (ELISAs) were coated with mPEG, HO-PEG, or t-BuO-PEG conjugates of the non-cross-reacting protein, porcine superoxide dismutase (SOD). In sera from rabbits immunized with HO-PEG conjugates of interferon-α or uricase, the ratio of titers of anti-PEG antibodies detected on mPEG-SOD over HO-PEG-SOD (“relative titer”) had a median of 1.1 (range 0.9–1.5). In contrast, sera from rabbits immunized with mPEG conjugates of three proteins had relative titers with a median of 3.0 (range 1.1–20). Analyses of sera from rabbits immunized with t-BuO-PEG-albumin showed that t-butoxy groups are more immunogenic than methoxy groups. Adding Tween 20 or Tween 80 to buffers used to wash the assay plates, as is often done in ELISAs, greatly reduced the sensitivity of detection of anti-PEG antibodies. Competitive ELISAs revealed that the affinities of antibodies raised against mPEG-uricase were c. 70 times higher for 10 kDa mPEG than for 10 kDa PEG diol and that anti-PEG antibodies raised against mPEG conjugates of three proteins had >1000 times higher affinities for albumin conjugates with c. 20 mPEGs than for analogous HO-PEG-albumin conjugates. Overall, these results are consistent with the hypothesis that antibodies with high affinity for methoxy groups contribute to the loss of efficacy of mPEG conjugates, especially if multiply-PEGylated. Using monofunctionally activated HO-PEG instead of mPEG in preparing conjugates for clinical use might decrease this undesirable effect. PMID:22332808

New optical probes for the continuous monitoring of renal function

NASA Astrophysics Data System (ADS)

Dorshow, Richard B.; Asmelash, Bethel; Chinen, Lori K.; Debreczeny, Martin P.; Fitch, Richard M.; Freskos, John N.; Galen, Karen P.; Gaston, Kimberly R.; Marzan, Timothy A.; Poreddy, Amruta R.; Rajagopalan, Raghavan; Shieh, Jeng-Jong; Neumann, William L.

2008-02-01

The ability to continuously monitor renal function via the glomerular filtration rate (GFR) in the clinic is currently an unmet medical need. To address this need we have developed a new series of hydrophilic fluorescent probes designed to clear via glomerular filtration for use as real time optical monitoring agents at the bedside. The ideal molecule should be freely filtered via the glomerular filtration barrier and be neither reabsorbed nor secreted by the renal tubule. In addition, we have hypothesized that a low volume of distribution into the interstitial space could also be advantageous. Our primary molecular design strategy employs a very small pyrazine-based fluorophore as the core unit. Modular chemistry for functionalizing these systems for optimal pharmacokinetics (PK) and photophysical properties have been developed. Structure-activity relationship (SAR) and pharmacokinetic (PK) studies involving hydrophilic pyrazine analogues incorporating polyethylene glycol (PEG), carbohydrate, amino acid and peptide functionality have been a focus of this work. Secondary design strategies for minimizing distribution into the interstitium while maintaining glomerular filtration include enhancing molecular volume through PEG substitution. In vivo optical monitoring experiments with advanced candidates have been correlated with plasma PK for measurement of clearance and hence GFR.

Conversion of rod-shaped gold nanoparticles to spherical forms and their effect on biodistribution in tumor-bearing mice.

PubMed

Akiyama, Yasuyuki; Mori, Takeshi; Katayama, Yoshiki; Niidome, Takuro

2012-10-11

Gold nanorods that have an absorption band in the near-infrared region and a photothermal effect have been used as nanodevices for near-infrared imaging and thermal therapy. Choice of the optimal shape of gold nanorods which relates optical properties and in vivo biodistribution is important for their applications. In the present study, to investigate the relationship between the shape of gold nanorods and their biodistribution after intravenous injection, we first prepared two types of gold nanorods that had distinct aspect ratios but had the same volume, zeta potential, and PEG density on the gold surface. Biodistributions of the two types of gold nanorods after intravenous injection into tumor-bearing mice were then compared. Although a slight difference in accumulation in the spleen was observed, no significant difference was observed in the liver, lung, kidney, and tumors. These results suggest that biodistribution of the gold nanorods in the aspect ratio range of 1.7 to 5.0, diameter of 10 to 50 nm, and volume of approximately 4 × 103 nm3 was dependent mainly on surface characteristics, PEG density, and zeta potential.

Characterization of a protein conjugate using an asymmetrical-flow field-flow fractionation and a size-exclusion chromatography with multi-detection system.

PubMed

Rebolj, Katja; Pahovnik, David; Zagar, Ema

2012-09-04

In this study we present detailed characterization of a protein-PEG conjugate using two separation techniques, that is, asymmetrical-flow field-flow fractionation (AF4) and size-exclusion chromatography (SEC), which were online coupled to a series of successively connected detectors: an ultraviolet, a multiangle light-scattering, a quasi-elastic light-scattering, and a refractive-index detector (UV-MALS(QELS)-RI). Matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used as a complementary characterization technique. The results of AF4 as well as SEC on two columns connected in series, with both separation techniques coupled to a multidetection system, indicate the uniform molar mass and chemical composition of the conjugate, that is, the molar ratio of protein to PEG is 1/1, the presence of minute amounts of residual unreacted protein and the aggregates with the same chemical composition as that of the conjugate. Since the portion of aggregated species is smaller in the acetate buffer solution containing 5% sorbitol than in the acetate buffer solution with 200-mM sodium chloride, the former buffer solution is more suitable for conjugate storage. The separation using only one SEC column results in poorly resolved peaks of the PEGylated protein conjugate and the aggregates, whereas MALDI-TOF MS analysis reveal the presence of the residual protein, but not the aggregates.

Hydrogel Delivery of Mesenchymal Stem Cell–Expressing Bone Morphogenetic Protein-2 Enhances Bone Defect Repair

PubMed Central

Hsiao, Hui-Yi; Yang, Shu-Rui; Brey, Eric M.; Chu, I-Ming

2016-01-01

Background: The application of bone tissue engineering for repairing bone defects has gradually shown some satisfactory progress. One of the concerns raising scientific attention is the poor supply of growth factors. A number of growth factor delivery approaches have been developed for promoting bone formation. However, there is no systematic comparison of those approaches on efficiency of neobone formation. In this study, the approaches using periosteum, direct supply of growth factors, or gene transfection of growth factors were evaluated to determine the osteogenic capacity on the repair of bone defect. Methods: In total, 42 male 21-week-old Sprague-Dawley rats weighing 250 to 400 g were used as the bone defect model to evaluate the bone repair efficiency. Various tissue engineered constructs of poly(ethylene glycol)-poly(l-lactic acid) (PEG-PLLA) copolymer hydrogel with periosteum, with external supply of bone morphogenetic protein-2 (BMP2), or with BMP2-transfected bone marrow–derived mesenchymal stem cells (BMMSCs) were filled in a 7-mm bone defect region. Animals were euthanized at 3 months, and the hydrogel constructs were harvested. The evaluation with histological staining and radiography analysis were performed for the volume of new bone formation. Results: The PEG-PLLA scaffold with BMMSCs promotes bone regeneration with the addition of periosteum. The group with BMP2-transfected BMMSCs demonstrated the largest volume of new bone among all the testing groups. Conclusions: Altogether, the results of this study provide the evidence that the combination of PEG-PLLA hydrogels with BMMSCs and sustained delivery of BMP2 resulted in the maximal bone regeneration. PMID:27622106

Evaluation of the Correlation Coefficient of Polyethylene Glycol Treated and Direct Prolactin Results and Comparability with Different Assay System Results.

PubMed

Pal, Shyamali

2017-12-01

The presence of Macro prolactin is a significant cause of elevated prolactin resulting in misdiagnosis in all automated systems. Poly ethylene glycol (PEG) pretreatment is the preventive process but such process includes the probability of loss of a fraction of bioactive prolactin. Surprisingly, PEG treated EQAS & IQAS samples in Cobas e 411 are found out to be correlating with direct results of at least 3 immunoassay systems and treated and untreated Cobas e 411 results are comparable by a correlation coefficient. Comparison of EQAS, IQAS and patient samples were done to find out the trueness of such correlation factor. Study with patient's results have established the correlation coefficient is valid for very small concentration of prolactin also. EQAS, IQAS and 150 patient samples were treated with PEG and prolactin results of treated and untreated samples obtained from Roche Cobas e 411. 25 patient's results (treated) were compared with direct results in Advia Centaur, Architect I & Access2 systems. Correlation coefficient was obtained from trend line of the treated and untreated results. Two tailed p-value obtained from regression coefficient(r) and sample size. The correlation coefficient is in the range (0.761-0.771). Reverse correlation range is (1.289-1.301). r value of two sets of calculated results were 0.995. Two tailed p- value is zero approving dismissal of null hypothesis. The z-score of EQAS does not always assure authenticity of resultsPEG precipitation is correlated by the factor 0.761 even in very small concentrationsAbbreviationsGFCgel filtration chromatographyPEGpolyethylene glycolEQASexternal quality assurance systemM-PRLmacro prolactinPRLprolactinECLIAelectro-chemiluminescence immunoassayCLIAclinical laboratory improvement amendmentsIQASinternal quality assurance systemrregression coefficient.

Purification, optimization of assay, and stability studies of dextransucrase isolated from Weissella cibaria JAG8.

PubMed

Mohan Rao, T Jagan; Goyal, Arun

2013-01-01

Dextransucrase-producing (Gen Bank accession no. KC110687) Weissella cibaria JAG8 was isolated from apple. The cell-free extract containing dextransucrase with specific activity of 1.0 U/mg was purified by polyethylene glycol (PEG). A concentration of 33% (v/v) PEG-400 fractionation gave a specific activity of 20.0 U/mg, whereas 15% (w/v) PEG-1500 resulted in a specific activity of 10.6 U/mg. The PEG-400-purified enzyme was further purified by chromatography using a Sephacryl S-300HR column, which resulted in 37-fold purification with 37 U/mg. The non-denaturing sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of column-purified enzyme showed a single homogenous band of 177 kDa by silver staining. The production of dextran was confirmed by in situ detection of the activity band using periodic acid-Schiff's base staining. The optimum assay conditions for dextransucrase were 35°C, pH 5.4, and 5.0% (w/v) sucrose concentration. The enzyme followed Michaelis-Menten kinetics with Km of 13 mM and Vmax 27.5 U/mg. The enzyme was stable in 10-500 mM sodium acetate buffer, pH 5.4. A 22% increase in enzyme activity was observed with 2 mM magnesium chloride; 64% loss in enzyme activity was observed with 10 mM ethylenediamine tetraacetic acid (EDTA), whereas a complete loss in activity was observed with 5 M urea. The dextransucrase was stable up to 35°C and pH of 5.4 for 1 hr.

Preparation, characterization, and in vitro activity evaluation of triblock copolymer-based polymersomes for drugs delivery

NASA Astrophysics Data System (ADS)

Besada, Lucas N.; Peruzzo, Pablo; Cortizo, Ana M.; Cortizo, M. Susana

2018-03-01

Polymersomes are polymer-based vesicles that form upon hydration of amphiphilic block copolymers and display high stability and durability, due to their mechanical and physical properties. They have hydrophilic reservoirs as well as thick hydrophobic membranes; allowing to encapsulate both water-soluble bioactive agent and hydrophobic drugs. In this study, poly ethylene glycol (PEG3350 and PEG6000) were used as hydrophilic part and poly(vinyl benzoate) (PVBz) as hydrophobic block to synthesize amphiphilic triblock copolymers (PVBz- b-PEG- b-PVBz). Different proportions of hydrophilic/hydrophobic part were assayed in order to obtain polymersomes by solvent injection method. For the synthesis of the copolymers, the initial block of PEG was derived to obtain a macroinitiator through a xanthate functional group (PEGX3 or PEGX6) and the polymerization of vinyl benzoate was carried out through reversible addition-fragmentation chain transfer polymerization (RAFT). The structure of PEGX and copolymers was confirmed by Infrared, 1H-NMR and UV-Vis spectrometry, while the average molecular weight (Mw) and polydispersity index (PI) were determined by size exclusion chromatography (SEC). The structures adopted by the copolymers in aqueous solution by self-assembly were investigated using transmission electron microscopy (TEM), dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS). Both techniques confirm that polymersomes were obtained for a fraction of hydrophilic block ( f) ≈ 35 ± 10%, with a diameter of 38.3 ± 0.3 nm or 22.5 ± 0.7 nm, as determined by TEM and according to the M w of the precursor block copolymer. In addition, we analyzed the possible cytotoxicity in view of its potential application as biomedical nanocarrier. The results suggest that polymersomes seem not induce cytotoxicity during the periods of time tested.

Measuring the fraction of pool volume filled with fine sediment

Treesearch

Sue Hilton; Thomas E. Lisle

1993-01-01

The fraction of pool volume filled with fine sediment (usually fine sand to medium gravel) can be a useful index of the sediment supply and substrate habitat of gravel-bed channels. It can be used to evaluate and monitor channel condition and to detect and evaluate sediment sources. This fraction (V*) is the ratio of fine-sediment volume to pool water volume plus fine-...

Characterization and Demonstrations of Laser-Induced Incandescence in both Normal and Low-Gravity

NASA Technical Reports Server (NTRS)

VanderWal, Randall L.

1997-01-01

Knowledge of soot volume fraction is important to a wide range of combustion studies in microgravity. Laser-induced incandescence (LII) offers high sensitivity, high temporal and spatial resolution in addition to geometric versatility for real-time determination of soot volume fraction. Implementation of LII into the 2.2 see drop tower at The NASA-Lewis Research Center along with system characterization is described. Absolute soot volume fraction measurements are presented for laminar and turbulent gas-jet flames in microgravity to illustrate the capabilities of LII in microgravity. Comparison between LII radial intensity profiles with soot volume fraction profiles determined through a full-field light extinction technique are also reported validating the accuracy of LII for soot volume fraction measurements in a microgravity environment.

Factors affecting the formation of eutectic solid dispersions and their dissolution behavior.

PubMed

Vippagunta, Sudha R; Wang, Zeren; Hornung, Stefanie; Krill, Steven L

2007-02-01

The objective of this work was to obtain a fundamental understanding of the factors, specifically the properties of poorly water-soluble drugs and water-soluble carriers, which influence predominantly, the formation of eutectic or monotectic crystalline solid dispersion and their dissolution behavior. A theoretical model was applied on five poorly water-soluble drugs (fenofibrate, flurbiprofen, griseofulvin, naproxen, and ibuprofen) having diverse physicochemical properties and water-soluble carrier (polyethylene glycol (PEG) 8000) for the evaluation of these factors. Of these, two drugs, fenofibrate and flurbiprofen, and PEG of different molecular weights (3350, 8000, and 20000), were chosen as model drugs and carriers for further investigation. Experimental phase diagrams were constructed and dissolution testing was performed to assess the performance of the systems. The theoretical model predicted the formation of eutectic or monotectic solid dispersions of fenofibrate, griseofulvin, ibuprofen, and naproxen with PEG, holding the contribution of specific intermolecular interactions between compound and carrier to zero. In the case of the flurbiprofen-PEG eutectic system, intermolecular interactions between drug and polymer needed to be taken into consideration to predict the experimental phase diagram. The results of the current work suggest that the thermodynamic function of melting point and heat of fusion (as a measure of crystal energy of drug) plays a significant role in the formation of a eutectic system. Lipophilicity of the compound (as represented by cLog P) was also demonstrated to have an effect. Specific interactions between drug and carrier play a significant role in influencing the eutectic composition. Molar volume of the drug did not seem to have an impact on eutectic formation. The polymer molecular weight appeared to have an impact on the eutectic composition for flurbiprofen, which exhibits specific interactions with PEG, whereas no such impact of polymer molecular weight on eutectic composition was observed for fenofibrate, which does not exhibit specific interactions with PEG. The impact of polymer molecular weight on dissolution of systems where specific drug-polymer interactions are exhibited was also observed. The current work provides valuable insight into factors affecting formation and dissolution of eutectic systems, which can facilitate the rational selection of suitable water-soluble carriers. Copyright (c) 2006 Wiley-Liss, Inc.

A randomized, controlled trial of oral sulfate solution plus polyethylene glycol as a bowel preparation for colonoscopy.

PubMed

Rex, Douglas K; McGowan, John; Cleveland, Mark vB; Di Palma, Jack A

2014-09-01

No bowel preparation for colonoscopy is optimal with regard to efficacy, safety, and tolerability. New options for bowel preparation are needed. To compare a new hybrid preparation consisting of a reduced dose of oral sulfate solution (OSS) plus 2 L of sulfate-free electrolyte lavage solution (SF-ELS) with 2 low-volume preparations based on polyethylene glycol electrolyte lavage solution (PEG-ELS). Two randomized, controlled trials. Twenty-four U.S. centers. A total of 737 outpatients undergoing colonoscopy. In study 1, OSS plus SF-ELS was given as a split dose, and in study 2, OSS plus SF-ELS was given in its entirety the evening before colonoscopy. In study 1, the active control was 2 L of PEG-ELS plus ascorbic acid (PEG-EA) given as a split dose. In study 2, the control was 10 mg of bisacodyl plus 2 L of SF-ELS taken the evening before colonoscopy. Rates of successful (good or excellent) bowel preparation. In study 1, the rates of successful (excellent or good) preparation with OSS plus SF-ELS and PEG-EA were identical at 93.5% for split-dose preparation. OSS plus SF-ELS was noninferior to PEG-EA (P < .001). In study 2, OSS plus SF-ELS resulted in successful preparation in 89.8% of patients compared with 83.5% with bisacodyl plus SF-ELS in a same-day preparation regimen. OSS plus SF-ELS was noninferior to bisacodyl plus SF-ELS (P <.001). In study 1, vomiting was more frequent with OSS plus SF-ELS (13.5% vs 6.7%; P = .042), and bloating was rated worse with PEG-EA (P = .025). In study 2, overall discomfort was rated worse with OSS plus SF-ELS (mean score 2.1 vs 1.8; P = .032). There were no deaths in either study and no serious adverse events considered related to the preparation. Bowel cleansing was not scored by colon segment. Adenoma detection was not compared between the regimens. OSS plus SF-ELS is a new, safe, and effective bowel preparation for colonoscopy. Copyright © 2014 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Assessment of interpatient heterogeneity in tumor radiosensitivity for nonsmall cell lung cancer using tumor-volume variation data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chvetsov, Alexei V., E-mail: chvetsov2@gmail.com; Schwartz, Jeffrey L.; Mayr, Nina

2014-06-15

Purpose: In our previous work, the authors showed that a distribution of cell surviving fractionsS{sub 2} in a heterogeneous group of patients could be derived from tumor-volume variation curves during radiotherapy for head and neck cancer. In this research study, the authors show that this algorithm can be applied to other tumors, specifically in nonsmall cell lung cancer. This new application includes larger patient volumes and includes comparison of data sets obtained at independent institutions. Methods: Our analysis was based on two data sets of tumor-volume variation curves for heterogeneous groups of 17 patients treated for nonsmall cell lung cancermore » with conventional dose fractionation. The data sets were obtained previously at two independent institutions by using megavoltage computed tomography. Statistical distributions of cell surviving fractionsS{sub 2} and clearance half-lives of lethally damaged cells T{sub 1/2} have been reconstructed in each patient group by using a version of the two-level cell population model of tumor response and a simulated annealing algorithm. The reconstructed statistical distributions of the cell surviving fractions have been compared to the distributions measured using predictive assays in vitro. Results: Nonsmall cell lung cancer presents certain difficulties for modeling surviving fractions using tumor-volume variation curves because of relatively large fractional hypoxic volume, low gradient of tumor-volume response, and possible uncertainties due to breathing motion. Despite these difficulties, cell surviving fractionsS{sub 2} for nonsmall cell lung cancer derived from tumor-volume variation measured at different institutions have similar probability density functions (PDFs) with mean values of 0.30 and 0.43 and standard deviations of 0.13 and 0.18, respectively. The PDFs for cell surviving fractions S{sub 2} reconstructed from tumor volume variation agree with the PDF measured in vitro. Conclusions: The data obtained in this work, when taken together with the data obtained previously for head and neck cancer, suggests that the cell surviving fractionsS{sub 2} can be reconstructed from the tumor volume variation curves measured during radiotherapy with conventional fractionation. The proposed method can be used for treatment evaluation and adaptation.« less

Assessment of interpatient heterogeneity in tumor radiosensitivity for nonsmall cell lung cancer using tumor-volume variation data.

PubMed

Chvetsov, Alexei V; Yartsev, Slav; Schwartz, Jeffrey L; Mayr, Nina

2014-06-01

In our previous work, the authors showed that a distribution of cell surviving fractions S2 in a heterogeneous group of patients could be derived from tumor-volume variation curves during radiotherapy for head and neck cancer. In this research study, the authors show that this algorithm can be applied to other tumors, specifically in nonsmall cell lung cancer. This new application includes larger patient volumes and includes comparison of data sets obtained at independent institutions. Our analysis was based on two data sets of tumor-volume variation curves for heterogeneous groups of 17 patients treated for nonsmall cell lung cancer with conventional dose fractionation. The data sets were obtained previously at two independent institutions by using megavoltage computed tomography. Statistical distributions of cell surviving fractions S2 and clearance half-lives of lethally damaged cells T(1/2) have been reconstructed in each patient group by using a version of the two-level cell population model of tumor response and a simulated annealing algorithm. The reconstructed statistical distributions of the cell surviving fractions have been compared to the distributions measured using predictive assays in vitro. Nonsmall cell lung cancer presents certain difficulties for modeling surviving fractions using tumor-volume variation curves because of relatively large fractional hypoxic volume, low gradient of tumor-volume response, and possible uncertainties due to breathing motion. Despite these difficulties, cell surviving fractions S2 for nonsmall cell lung cancer derived from tumor-volume variation measured at different institutions have similar probability density functions (PDFs) with mean values of 0.30 and 0.43 and standard deviations of 0.13 and 0.18, respectively. The PDFs for cell surviving fractions S2 reconstructed from tumor volume variation agree with the PDF measured in vitro. The data obtained in this work, when taken together with the data obtained previously for head and neck cancer, suggests that the cell surviving fractions S2 can be reconstructed from the tumor volume variation curves measured during radiotherapy with conventional fractionation. The proposed method can be used for treatment evaluation and adaptation.

Lithium Polymer Electrolytes Based On PMMA / PEG And Penetrant Diffusion In Kraton Penta-Block Ionomer

NASA Astrophysics Data System (ADS)

Meng, Yan

The study of diffusion in polymeric material is critical to many research fields and applications, such as polymer morphology, protective coatings (paints and varnishes), separation membranes, transport phenomena, polymer electrolytes, polymer melt, and controlled release of drugs from polymer carriers [1-9]. However, it is still a challenge to understand, predict and control the diffusion of molecules and ions of different sizes in polymers [2]. This work studied the medium to long range diffusion of species (i.e., ions and molecules) in solid polymer electrolytes based on poly(ethylene glycol)/poly(methyl methacrylate) (PEG/PMMA) for Li-based batteries, and polymeric permselective membranes via pulsed-field gradient NMR and a.c. impedance. Over the past decades polymer electrolytes have attracted much attention because of their promising technological application as an ion-conducting medium in solid-state batteries, fuel cells, electrochromic displays, and chemical sensors [10, 11]. However, despite numerous studies related to ionic transport in these electrolytes the understanding of the migration mechanism is still far from being complete, and progress in the field remains largely empirical [10, 12-15]. Among various candidates for solid polymer electrolyte (SPE) material, the miscible polymer pair, poly(ethylene oxide)/poly(methyl methacrylate) (PEO/PMMA), is an attractive one, because there is a huge difference in mobility between PEO and PMMA in their blends, and PEO chains remain exceptionally mobile in the blend even at temperature below the glass transition temperature of the blend [ 16]. Thus the mechanical strength and dimensional stability is maintained by PMMA component, while the chain motions or rearrangements of the PEO component virtually contribute to the ion transport [17]. The current work prepared two types of SPE based on poly(ethylene glycol) (PEG) /PMMA (40/60 by weight) for Li-based batteries: lithium bis(trifluoromethylsulfonylimide) (LiN(SO2CF3)2, LiTFSI) doped SPE and single-ion SPE. PEG, which is the very low molecular weight version of PEO, was used instead of PLO due to PEG's advantages of being noncrystalline, higher mobility, and having relatively high ionic conductivity when doped with alkali metal salts [18]. The medium to long range diffusion of species (i.e., ions and molecules) were studied via pulsed-field gradient NMR and a.c. impedance, along with other properties. For the LiTFSI doped system, the samples are named with their F0 to Li ratios. The order of diffusivity of ions is 16:1> 24:1> 8:1, while the order of a.c. conductivity is 24:1 > 16:1> 8:1. The largest diffusion 7Li coefficient is 1.4 x 108 cm 2/s in 16:1 at 77°C , and the largest a.c. conductivity is 1.43x 10-5S/cm for 24:1 at 68°C. The discrepancy between the diffusivity order and conductivity order is attributed to the formation of neutral contact ion pairs by a substantial fraction of ions in 16:1 . As the salt concentration is increased as 24:1→16:1→8:1, there is the transition of mostly free ions (i.e., 24:1)→free ions+contact ion pairs (i.e.. 16:1)→free ions+contact ion pairs+higher aggregates (i.e., 8:1). For the single-ion system, ion pairing of lithium PMMA ionomer is a serious problem due to the relatively low acidity of its corresponding acid and the low dielectric constant of the solvent (i.e. PEG). The Li+ diffusivity is fair (on the order of 10-8 cm2/s at 65°C, 77°C, and 89°C), but the fraction of free Li+ is only 1-2%. This severely limits the resulting a.c. conductivity, which is 2.72x 10-7 S/cm for 40P600 at 81°C. The second project involves studying the transport properties of a sulfonated pentablock copolymer, poly(para-methylstyrene)--b-hydrogenated polybutadiene-b-polystyrene-bhydrogenated polybutadiene - b-poly(para-methylstyrene) with polystyrene sulfonated in the midblock(PMS-HPB-sS-HPB-PMS), as pemrselective membranes for protective clothing, with high permeability to water and low permeability to hazardous organic chemicals. In addition, this work also contributes to study of polymer electrolyte membrane for fuel cell systems, because water transport in polymer electrolyte membranes (PEMs) has a profound effect on the performance of a fuel cell, yet is surprisingly the least studied property of PEMs[19]. The self-diffusion coefficients of different penetrant molecules, i.e., water, dimethyl methylphosphonate (DMMP), and ethanol in the said ionomer were accurately measured with PFG NMR as functions of temperature and concentration of solvents. Water exhibited self-diffusion coefficients two orders of magnitude higher than DMMP, while ethanol lies in between. Their effective volume to surface ratios of domains where diffusion took place were determined. The volume to surface ratios of water and DMMP are quite different, suggesting they may have different local geometry of the pores they reside in, while the V p/Seff ratios for water and ethanol are similar, thereby suggesting similar local environments of these solvents in the ionomer.

A nonchromatographic process for purification of secretory immunoglobulins from caprine whey.

PubMed

Matlschweiger, Alexander; Himmler, Gottfried; Linhart, Clemens; Harasek, Michael; Hahn, Rainer

2017-05-01

Secretory immunoglobulins are an important antibody class being primarily responsible for immunoprotection of mucosal surfaces. A simple, non-chromatographic purification process for secretory immunoglobulins from caprine whey was developed. In the first process step whey was concentrated 30-40-fold on a 500 kDa membrane, thereby increasing the purity from 3% to 15%. The second step consisted of a fractionated PEG precipitation, in which high molecular weight impurities were removed first and in the second stage the secretory immunoglobulins were precipitated, leaving a majority of the low molecular weight proteins in solution. The re-dissolved secretory immunoglobulin fraction had a purity of 43% which could then be increased to 72% by diafiltration at a volume exchange factor of 10. Further increase of purity was only possible at the expense of very high buffer consumption. If diafiltration was performed directly after ultrafiltration, followed by precipitation, the yield was higher but purity was only 54%. Overall, filtration performance was characterized by high concentration polarization, therefore process conditions were set to low trans-membrane pressure and moderate protein concentration. As such purity and to a lesser extent throughput were the major objectives rather than yield, since whey, as a by-product of the dairy industry, is a cheap raw material of almost unlimited supply. Ultra-/diafiltration performance was described well by correlations using dimensionless numbers. Compared with a theoretical model (Graetz/Leveque solution) the flux was slightly overestimated. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:642-653, 2017. © 2017 American Institute of Chemical Engineers.

Effect of volume fraction of alpha and transformed beta on the high cycle fatigue properties of bimodal Ti6Al4V alloy

NASA Astrophysics Data System (ADS)

Jadhav, Shital; Powar, Amit; Patil, Sandip; Supare, Ashish; Farane, Bhagwan; Singh, Rajkumar, Dr.

2017-05-01

The present study was performed to investigate the effect of volume fraction of alpha and transformed beta phase on the high-cycle fatigue (HCF) properties of the bimodal titanium Ti6Al4V alloy. The effect of such morphology on mechanical properties was studied using tensile and rotating bending fatigue test as per ASTM standards. Microstructures and fractography of the specimens were studied using optical and scanning electron microscopy (SEM) respectively.Ti6Al4V alloy samples were heat treated to have three distinctive volume fractions of alpha and transformed beta phase. With an increase in quench delay from 30,50 and 70 sec during quenching after solutionizing temperature of 967°C, the volume fraction of alpha was found to be increased from 20% to 67%. Tests on tensile and rotating bending fatigue showed that the specimen with 20% volume fraction of alpha phase exhibited the highest tensile and fatigue strength, however the properties gets deteriorate with increase in volume fraction of alpha.

An experimental study on rheological behavior of a nanofluid containing oxide nanoparticle and proposing a new correlation

NASA Astrophysics Data System (ADS)

Saeedi, Amir Hussein; Akbari, Mohammad; Toghraie, Davood

2018-05-01

In this paper, the nanofluid dynamic viscosity composed of CeO2- Ethylene Glycol is examined within 25-50 °C with 5 °C intervals and at six volume fractions (0.05, 0.1, 0.2, 0.4, 0.8 and 1.2%) experimentally. The nanofluid was exposed to ultrasound waves for various durations to study the effect of this parameter on dynamic viscosity of the fluid. We found that at a constant temperature, nanofluid viscosity increases with increases in the volume fraction of the nanoparticles. Also, at a given volume fraction, nanofluid viscosity decreases when temperature is increased. Maximum increase in nanofluid viscosity compared to the base fluid viscosity occurs at 25 °C and volume fraction of 1.2%. It can be inferred that the obtained mathematical relationship is a suitable predicting model for estimating dynamic viscosity of CeO2- Ethylene Glycol (EG) at different volume fractions and temperatures and its results are consistent to laboratory results in the set volume fraction and temperature ranges.

Hepatocellular Carcinoma: Intra-arterial Delivery of Doxorubicin-loaded Hollow Gold Nanospheres for Photothermal Ablation—Chemoembolization Therapy in Rats

PubMed Central

Li, Junjie; Zhou, Min; Liu, Fengyong; Xiong, Chiyi; Wang, Wanqin; Cao, Qizhen; Wen, Xiaoxia; Robertson, J. David; Ji, Xin; Wang, Y. Andrew; Gupta, Sanjay

2016-01-01

Purpose To determine if combretastatin A-4 phosphate disodium (CA4P) can enhance the tumor uptake of doxorubicin (Dox)-loaded, polyethylene glycol (PEG)–coated hollow gold nanospheres (HAuNS) mixed with ethiodized oil for improved photothermal ablation (PTA)–chemoembolization therapy (CET) of hepatocellular carcinoma (HCC) in rats. Materials and Methods Animal experiments were approved by the institutional animal care and use committee and performed from February 2014 to April 2015. Male Sprague-Dawley rats (n = 45; age, 12 weeks) were inoculated with N1S1 HCC cells in the liver, and 8 days later, were randomly divided into two groups of 10 rats. Group 1 rats received intrahepatic arterial injection of PEG-HAuNS and ethiodized oil alone; group 2 received pretreatment with CA4P and injection of PEG-HAuNS and ethiodized oil 5 minutes later. The gold content of tumor and liver tissue at 1 hour or 24 hours after injection was quantified by using neutron activation analysis (n = 5 per time point). Five rats received pretreatment CA4P, PEG-copper 64-HAuNS, and ethiodized oil and underwent micro–positron emission tomography (PET)/computed tomography (CT). In a separate study, three groups of six rats with HCC were injected with saline solution (control group); CA4P, Dox-loaded PEG-coated HAuNS (Dox@PEG-HAuNS), and ethiodized oil (CET group); or CA4P, Dox@PEG-HAuNS, ethiodized oil, and near-infrared irradiation (PTA-CET group). Temperature was recorded during laser irradiation. Findings were verified at postmortem histopathologic and/or autoradiographic examination. Wilcoxon rank-sum test and Pearson correlation analyses were performed. Results PEG-HAuNS uptake in CA4P-pretreated HCC tumors was significantly higher than that in non–CA4P-pretreated tumors at both 1 hour (P < .03) and 24 hours (P < .01). Mean ± standard deviation of tumor-to-liver PEG-HAuNS uptake ratios at 1 hour and 24 hours, respectively, were 5.63 ± 3.09 and 1.68 ± 0.77 in the CA4P-treated group and 1.29 ± 2.40 and 0.14 ± 0.11 in the non–CA4P-treated group. Micro-PET/CT allowed clear delineation of tumors, enabling quantitative imaging analysis. Laser irradiation increased temperature to 60°C and 43°C in the tumor and adjacent liver, respectively. Mean HCC tumor volumes 10 days after therapy were 1.68 cm3 ± 1.01, 3.96 cm3 ± 1.75, and 6.13 cm3 ± 2.27 in the PTA-CET, CET, and control groups, respectively, with significant differences between the PTA-CET group and other groups (P < .05). Conclusion CA4P pretreatment caused a higher concentration of Dox@PEG-HAuNS to be trapped inside the tumor, thereby enhancing the efficacy of anti–HCC treatment with PTA-CET in rats. © RSNA, 2016 Online supplemental material is available for this article. PMID:27347765

Hepatocellular Carcinoma: Intra-arterial Delivery of Doxorubicin-loaded Hollow Gold Nanospheres for Photothermal Ablation-Chemoembolization Therapy in Rats.

PubMed

Li, Junjie; Zhou, Min; Liu, Fengyong; Xiong, Chiyi; Wang, Wanqin; Cao, Qizhen; Wen, Xiaoxia; Robertson, J David; Ji, Xin; Wang, Y Andrew; Gupta, Sanjay; Li, Chun

2016-11-01

Purpose To determine if combretastatin A-4 phosphate disodium (CA4P) can enhance the tumor uptake of doxorubicin (Dox)-loaded, polyethylene glycol (PEG)-coated hollow gold nanospheres (HAuNS) mixed with ethiodized oil for improved photothermal ablation (PTA)-chemoembolization therapy (CET) of hepatocellular carcinoma (HCC) in rats. Materials and Methods Animal experiments were approved by the institutional animal care and use committee and performed from February 2014 to April 2015. Male Sprague-Dawley rats (n = 45; age, 12 weeks) were inoculated with N1S1 HCC cells in the liver, and 8 days later, were randomly divided into two groups of 10 rats. Group 1 rats received intrahepatic arterial injection of PEG-HAuNS and ethiodized oil alone; group 2 received pretreatment with CA4P and injection of PEG-HAuNS and ethiodized oil 5 minutes later. The gold content of tumor and liver tissue at 1 hour or 24 hours after injection was quantified by using neutron activation analysis (n = 5 per time point). Five rats received pretreatment CA4P, PEG-copper 64-HAuNS, and ethiodized oil and underwent micro-positron emission tomography (PET)/computed tomography (CT). In a separate study, three groups of six rats with HCC were injected with saline solution (control group); CA4P, Dox-loaded PEG-coated HAuNS (Dox@PEG-HAuNS), and ethiodized oil (CET group); or CA4P, Dox@PEG-HAuNS, ethiodized oil, and near-infrared irradiation (PTA-CET group). Temperature was recorded during laser irradiation. Findings were verified at postmortem histopathologic and/or autoradiographic examination. Wilcoxon rank-sum test and Pearson correlation analyses were performed. Results PEG-HAuNS uptake in CA4P-pretreated HCC tumors was significantly higher than that in non-CA4P-pretreated tumors at both 1 hour (P < .03) and 24 hours (P < .01). Mean ± standard deviation of tumor-to-liver PEG-HAuNS uptake ratios at 1 hour and 24 hours, respectively, were 5.63 ± 3.09 and 1.68 ± 0.77 in the CA4P-treated group and 1.29 ± 2.40 and 0.14 ± 0.11 in the non-CA4P-treated group. Micro-PET/CT allowed clear delineation of tumors, enabling quantitative imaging analysis. Laser irradiation increased temperature to 60°C and 43°C in the tumor and adjacent liver, respectively. Mean HCC tumor volumes 10 days after therapy were 1.68 cm 3 ± 1.01, 3.96 cm 3 ± 1.75, and 6.13 cm 3 ± 2.27 in the PTA-CET, CET, and control groups, respectively, with significant differences between the PTA-CET group and other groups (P < .05). Conclusion CA4P pretreatment caused a higher concentration of Dox@PEG-HAuNS to be trapped inside the tumor, thereby enhancing the efficacy of anti-HCC treatment with PTA-CET in rats. © RSNA, 2016 Online supplemental material is available for this article.

The effect on colon visualization during colonoscopy of the addition of simethicone to polyethylene glycol-electrolyte solution: a randomized single-blind study.

PubMed

Matro, Rebecca; Tupchong, Keegan; Daskalakis, Constantine; Gordon, Victoria; Katz, Leo; Kastenberg, David

2012-11-29

Colonic bubbles associated with polyethylene glycol-electrolyte solution (PEG-ELS) are common and obscure mucosal visualization. This study aimed to determine whether adding simethicone decreases the incidence of bubbles. Prospective, single-blind, randomized comparison of split dose PEG-ELS vs. PEG-ELS+simethicone (PEG-S) for outpatient colonoscopy. Bubble severity for colonic segments was assessed on withdrawal as A=no/minimal bubbles, B=moderate bubbles/interfere with detecting 5 mm polyp, C=severe bubbles/interfere with detecting 10 mm polyp. Primary end point was Grade B or C bubbles in any colon segment. Secondary end points were cleansing quality, incidence and severity of side effects, and polyp detection. One hundred and thirty nine patients enrolled; 13 withdrew before colonoscopy. Of 123 patients evaluated, 62 took PEG-S and 61 PEG-ELS. The incidence of grade B or C bubbles was much lower with PEG-S compared with PEG-ELS (2% vs. 38%; P=0.001). Overall cleansing (excellent or good) quality was not significantly different for either the whole colon (89% PEG-ELS, 94% of PEG-S, P=0.529) or right colon (88% PEG-ELS, 94% PEG-S, P=0.365). More PEG-S patients had excellent rather than good preps (whole colon 53% vs. 28%, P=0.004; right colon 53% vs. 35%, P=0.044). Need for any flushing was less with PEG-S (38% vs. 70%, P=0.001). The groups were not significantly different with respect to total procedure and withdrawal times, incidence or severity of side effects, or number of polyps/patient or adenomas/patient. Adding simethicone to PEG-ELS effectively eliminates bubbles, substantially reduces the need for flushing, and results in more excellent preparations.

The Effect on Colon Visualization During Colonoscopy of the Addition of Simethicone to Polyethylene Glycol-Electrolyte Solution: A Randomized Single-Blind Study

PubMed Central

Matro, Rebecca; Tupchong, Keegan; Daskalakis, Constantine; Gordon, Victoria; Katz, Leo; Kastenberg, David

2012-01-01

OBJECTIVES: Colonic bubbles associated with polyethylene glycol-electrolyte solution (PEG-ELS) are common and obscure mucosal visualization. This study aimed to determine whether adding simethicone decreases the incidence of bubbles. METHODS: Prospective, single-blind, randomized comparison of split dose PEG-ELS vs. PEG-ELS+simethicone (PEG-S) for outpatient colonoscopy. Bubble severity for colonic segments was assessed on withdrawal as A=no/minimal bubbles, B=moderate bubbles/interfere with detecting 5 mm polyp, C=severe bubbles/interfere with detecting 10 mm polyp. Primary end point was Grade B or C bubbles in any colon segment. Secondary end points were cleansing quality, incidence and severity of side effects, and polyp detection. RESULTS: One hundred and thirty nine patients enrolled; 13 withdrew before colonoscopy. Of 123 patients evaluated, 62 took PEG-S and 61 PEG-ELS. The incidence of grade B or C bubbles was much lower with PEG-S compared with PEG-ELS (2% vs. 38% P=0.001). Overall cleansing (excellent or good) quality was not significantly different for either the whole colon (89% PEG-ELS, 94% of PEG-S, P=0.529) or right colon (88% PEG-ELS, 94% PEG-S, P=0.365). More PEG-S patients had excellent rather than good preps (whole colon 53% vs. 28%, P=0.004; right colon 53% vs. 35%, P=0.044). Need for any flushing was less with PEG-S (38% vs. 70%, P=0.001). The groups were not significantly different with respect to total procedure and withdrawal times, incidence or severity of side effects, or number of polyps/patient or adenomas/patient. CONCLUSIONS: Adding simethicone to PEG-ELS effectively eliminates bubbles, substantially reduces the need for flushing, and results in more excellent preparations. PMID:23238113

Addition of simethicone improves small bowel capsule endoscopy visualisation quality.

PubMed

Krijbolder, M S; Grooteman, K V; Bogers, S K; de Jong, D J

2018-01-01

Small bowel capsule endoscopy (SBCE) is an important diagnostic tool for small-bowel diseases but its quality may be hampered by intraluminal gas. This study evaluated the added value of the anti-foaming agent, simethicone, to a bowel preparation with polyethylene glycol (PEG) on the quality of small bowel visualisation and its use in the Netherlands. This was a retrospective, single-blind, cohort study. Patients in the PEG group only received PEG prior to SBCE. Patients in the PEG-S group ingested additional simethicone. Two investigators assessed the quality of small-bowel visualisation using a four-point scale for 'intraluminal gas' and 'faecal contamination'. By means of a survey, the use of anti-foaming agents was assessed in a random sample of 16 Dutch hospitals performing SBCE. The quality of small bowel visualisation in the PEG group (n = 33) was significantly more limited by intraluminal gas when compared with the PEG-S group (n = 31): proximal segment 83.3% in PEG group vs. 18.5% in PEG-S group (p < 0.01), distal segment 66.7% vs. 18.5% respectively (p < 0.01). No difference was observed in the amount of faecal contamination (proximal segment 80.0% PEG vs. 59.3% PEG-S, p = 0.2; distal segment 90.0% PEG vs. 85.2% PEG-S, p = 0.7), mean small bowel transit times (4.0 PEG vs. 3.9 hours PEG-S, p = 0.7) and diagnostic yield (43.3% PEG vs. 22.2% PEG-S, p = 0.16). Frequency of anti-foaming agent use in the Netherlands was low (3/16, 18.8%). Simethicone is of added value to a PEG bowel preparation in improving the quality of visualisation of the small bowel by reducing intraluminal gas. At present, the use of anti-foaming agents in SBCE preparation is not standard practice in the Netherlands.

A discrete model of Ostwald ripening based on multiple pairwise interactions

NASA Astrophysics Data System (ADS)

Di Nunzio, Paolo Emilio

2018-06-01

A discrete multi-particle model of Ostwald ripening based on direct pairwise interactions is developed for particles with incoherent interfaces as an alternative to the classical LSW mean field theory. The rate of matter exchange depends on the average surface-to-surface interparticle distance, a characteristic feature of the system which naturally incorporates the effect of volume fraction of second phase. The multi-particle diffusion is described through the definition of an interaction volume containing all the particles involved in the exchange of solute. At small volume fractions this is proportional to the size of the central particle, at higher volume fractions it gradually reduces as a consequence of diffusion screening described on a geometrical basis. The topological noise present in real systems is also included. For volume fractions below about 0.1 the model predicts broad and right-skewed stationary size distributions resembling a lognormal function. Above this value, a transition to sharper, more symmetrical but still right-skewed shapes occurs. An excellent agreement with experiments is obtained for 3D particle size distributions of solid-solid and solid-liquid systems with volume fraction 0.07, 0.30, 0.52 and 0.74. The kinetic constant of the model depends on the cube root of volume fraction up to about 0.1, then increases rapidly with an upward concavity. It is in good agreement with the available literature data on solid-liquid mixtures in the volume fraction range from 0.20 to about 0.75.

Experimental investigation on thermal conductivity and viscosity of maghemite (γ –Fe2O3) water-based nanofluids

NASA Astrophysics Data System (ADS)

Nurdin, I.; Johan, M. R.; Ang, B. C.

2018-03-01

Thermal conductivity and kinematic viscosity of maghemite nanofluids were experimentally investigated at a small volume fraction of maghemite nanoparticles and temperatures. Maghemite nanofluids were prepared by suspending maghemite nanoparticles in water as base fluids. Results show that the thermal conductivity of maghemite nanofluids linearly increase with increasing particle volume fraction and temperature, while kinematic viscosity increase with increasing particle volume fraction and decrease with increasing temperature. The highest enhancement of thermal conductivity and kinematic viscosity are 18.84% and 13.66% respectively, at particle volume fraction 0.6% and temperature 35.

Predicting Morphology of Polymers Using Mesotek+

DTIC Science & Technology

2010-02-01

file is then produced for Mesotek+ to reproduce the phase behavior for an experimental system of poly (styrene-b- isoprene ) in the solvent tetradecane...theoretical code 3a and (b) experimental code 3b. .....6  Figure 3. Results from 40/60 volume styrene-b- isoprene + tetradecane using gnuplot: A...styrene volume fraction, B) isoprene volume fraction, and C) tetradecane volume fraction. The color bar to the right of each plot indicates how the

Mechanically robust cryogels with injectability and bioprinting supportability for adipose tissue engineering.

PubMed

Qi, Dianjun; Wu, Shaohua; Kuss, Mitchell A; Shi, Wen; Chung, Soonkyu; Deegan, Paul T; Kamenskiy, Alexey; He, Yini; Duan, Bin

2018-05-26

Bioengineered adipose tissues have gained increased interest as a promising alternative to autologous tissue flaps and synthetic adipose fillers for soft tissue augmentation and defect reconstruction in clinic. Although many scaffolding materials and biofabrication methods have been investigated for adipose tissue engineering in the last decades, there are still challenges to recapitulate the appropriate adipose tissue microenvironment, maintain volume stability, and induce vascularization to achieve long-term function and integration. In the present research, we fabricated cryogels consisting of methacrylated gelatin, methacrylated hyaluronic acid, and 4arm poly(ethylene glycol) acrylate (PEG-4A) by using cryopolymerization. The cryogels were repeatedly injectable and stretchable, and the addition of PEG-4A improved the robustness and mechanical properties. The cryogels supported human adipose progenitor cell (HWA) and adipose derived mesenchymal stromal cell adhesion, proliferation, and adipogenic differentiation and maturation, regardless of the addition of PEG-4A. The HWA laden cryogels facilitated the co-culture of human umbilical vein endothelial cells (HUVEC) and capillary-like network formation, which in return also promoted adipogenesis. We further combined cryogels with 3D bioprinting to generate handleable adipose constructs with clinically relevant size. 3D bioprinting enabled the deposition of multiple bioinks onto the cryogels. The bioprinted flap-like constructs had an integrated structure without delamination and supported vascularization. Adipose tissue engineering is promising for reconstruction of soft tissue defects, and also challenging for restoring and maintaining soft tissue volume and shape, and achieving vascularization and integration. In this study, we fabricated cryogels with mechanical robustness, injectability, and stretchability by using cryopolymerization. The cryogels promoted cell adhesion, proliferation, and adipogenic differentiation and maturation of human adipose progenitor cells and adipose derived mesenchymal stromal cells. Moreover, the cryogels also supported 3D bioprinting on top, forming vascularized adipose constructs. This study demonstrates the potential of the implementation of cryogels for generating volume-stable adipose tissue constructs and provides a strategy to fabricate vascularized flap-like constructs for complex soft tissue regeneration. Copyright © 2018. Published by Elsevier Ltd.

Formation of protein complex with the aid of polyethylene glycol for deproteinized natural rubber latex

NASA Astrophysics Data System (ADS)

Wei, Lim Keuw; Ing, Wong Kwee; Badri, Khairiah Haji; Ban, Wong Chong

2013-11-01

The effect of polyethylene glycol (PEG) as a deproteinizing agent in commercial natural rubber latex (NRL) onto the physicochemical properties of the NRL was investigated. Three types of PEG were used namely PEG200, PEG4000 and PEG20000 (molecular weight of 200, 4000 and 20000 g/mol respectively). The optimum amount of PEG in NRL was determined from viscosity changes, protein content and Fourier Transform Infrared spectroscopy. Level of protein reduction was affected by molecular weight of PEG. The addition of PEG in NRL reduced the protein content of NRL (3.30 %) to the lowest (2.01 %) at 0.40 phr of PEG200 due to more attractive hydrophobic interactions between short chains PEG compared to PEG4000 (2.24%) and PEG20000 (2.15%). This was verified through FTIR spectroscopy analysis by observing the primary and secondary amide peak where PEG4000 has lesser absorption at the region compared to with PEG20000.

[Course of ejection fraction, regurgitation fraction and ventricular volumes during exertion in chronic aortic insufficiency. Study using technetium 99m gamma-cineangiography].

PubMed

Bassand, J P; Faivre, R; Berthout, P; Cardot, J C; Verdenet, J; Bidet, R; Maurat, J P

1985-06-01

Previous studies have shown that variations of the ejection fraction (EF) during exercise were representative of the contractile state of the left ventricle: an increased EF on effort is considered to be physiological, whilst a decrease would indicate latent LV dysfunction unmasked during exercise. This hypothesis was tested by performing Technetium 99 gamma cineangiography at equilibrium under basal conditions and at maximal effort in 8 healthy subjects and 44 patients with pure, severe aortic regurgitation to measure the ejection and regurgitant fractions and the variations in end systolic and end diastolic LV volume. In the control group the EF increased and end systolic volume decreased significantly on effort whilst the regurgitant fraction and end diastolic volume were unchanged. In the 44 patients with aortic regurgitation no significant variations in EF, end systolic and end diastolic volumes were observed because the individual values were very dispersed. Variations of the EF and end systolic volume were inversely correlated. The regurgitant fraction decreased significantly on effort. Based on the variations of the EF and end systolic volume three different types of response to effort could be identified: in 7 patients, the EF increased on effort and end systolic volume decreased without any significant variation in the end diastolic volume, as in the group of normal control subjects; in 22 patients, a reduction in EF was observed on effort, associated with an increased end systolic volume. These changes indicated latent IV dysfunction inapparent at rest and unmasked by exercise; in a third group of 15 patients, the EF decreased on effort despite a physiological decrease in end systolic volume due to a greater decrease in end diastolic volume.(ABSTRACT TRUNCATED AT 250 WORDS)

How the dispersion of magnesium oxide nanoparticles effects on the viscosity of water-ethylene glycol mixture: Experimental evaluation and correlation development

NASA Astrophysics Data System (ADS)

Afrand, Masoud; Abedini, Ehsan; Teimouri, Hamid

2017-03-01

In this paper, the effect of dispersion of magnesium oxide nanoparticles on viscosity of a mixture of water and ethylene glycol (50-50% vol.) was examined experimentally. Experiments were performed for various nanofluid samples at different temperatures and shear rates. Measurements revealed that the nanofluid samples with volume fractions of less than 1.5% had Newtonian behavior, while the sample with volume fraction of 3% showed non-Newtonian behavior. Results showed that the viscosity of nanofluids enhanced with increasing nanoparticles volume fraction and decreasing temperature. Results of sensitivity analysis revealed that the viscosity sensitivity of nanofluid samples to temperature at higher volume fractions is more than that of at lower volume fractions. Finally, because of the inability of the existing model to predict the viscosity of MgO/EG-water nanofluid, an experimental correlation has been proposed for predicting the viscosity of the nanofluid.

A novel diblock of copolymer of (monomethoxy poly [ethylene glycol]-oleate) with a small hydrophobic fraction to make stable micelles/polymersomes for curcumin delivery to cancer cells

PubMed Central

Erfani-Moghadam, Vahid; Nomani, Alireza; Zamani, Mina; Yazdani, Yaghoub; Najafi, Farhood; Sadeghizadeh, Majid

2014-01-01

Curcumin is a potent natural anticancer agent, but its effectiveness is limited by properties such as very low solubility, high rate of degradation, and low rate of absorption of its hydrophobic molecules in vivo. To date, various nanocarriers have been used to improve the bioavailability of this hydrophobic biomaterial. This study investigates the encapsulation of curcumin in a novel nanostructure of monomethoxy poly(ethylene glycol)-oleate (mPEG-OA) and its anticancer effect. Tests were done to determine the critical micelle concentration (CMC), encapsulation efficiency, drug-loading efficiency, and cytotoxicity (against U87MG brain carcinoma cells and HFSF-PI3 cells as normal human fibroblasts) of some nanodevice preparations. The results of fluorescence microscopy and cell-cycle analyses indicated that the in vitro bioavailability of the encapsulated curcumin was significantly greater than that of free curcumin. Cytotoxicity evaluations showed that half maximal inhibitory concentrations of free curcumin and curcumin-loaded mPEG-OA for the U87MG cancer cell line were 48 μM and 24 μM, respectively. The Annexin-V-FLUOS assay was used to quantify the apoptotic effect of the prepared nanostructures. Apoptosis induction was observed in a dose-dependent manner after curcumin-loaded mPEG-OA treatments. Two common self-assembling structures, micelles and polymersomes, were observed by atomic force microscopy and dynamic light scattering, and the abundance of each structure was dependent on the concentration of the diblock copolymer. The mPEG-OA micelles had a very low CMC (13.24 μM or 0.03 g/L). Moreover, atomic force microscopy and dynamic light scattering showed that the curcumin-loaded mPEG-OA polymersomes had very stable structures, and at concentrations 1,000 times less than the CMC, at which the micelles disappear, polymersomes were the dominant structures in the dispersion with a reduced size distribution below 150 nm. Overall, the results from these tests revealed that this nanocarrier can be considered as an appropriate drug delivery system for delivering curcumin to cancer cells. PMID:25489242

Near-infrared (1550 nm) in vivo bioimaging based on rare-earth doped ceramic nanophosphors modified with PEG-b-poly(4-vinylbenzylphosphonate)

NASA Astrophysics Data System (ADS)

Kamimura, Masao; Kanayama, Naoki; Tokuzen, Kimikazu; Soga, Kohei; Nagasaki, Yukio

2011-09-01

A novel poly(ethylene glycol) (PEG)-based block copolymer possessing a 4-vinylbenzylphosphonate repeating unit in another segment (PEG-block-poly(4-vinylbenzylphosphonate)) (PEG-b-PVBP) was designed and successfully synthesized. As a control, an end-functionalized PEG possessing a mono-phosphonate group (PEG-PO3H2) was also synthesized. The surface of near-infrared (NIR) phosphors (i.e., ytterbium (Yb) and erbium (Er) ion-codoped Y2O3 nanoparticles (YNPs)) were modified with PEG-b-PVBP (PEG-YNP(b)s) and PEG-PO3H2 (PEG-YNP(1)s). The adsorption of PEG-b-PVBP and PEG-PO3H2 was estimated by Fourier transform infrared (FT-IR) measurements and thermal gravimetric analysis (TGA). The physicochemical characteristics of the obtained YNP samples were analyzed by ζ-potential and dynamic light scattering (DLS) measurements. The ζ-potentials of YNPs modified by these polymers were close to zero, indicating the effective coverage of the YNP surface by our new PEG derivatives. However, the dispersion stability of the PEGylated YNPs was strongly affected by the structure of the PEG terminus. The average diameter of the PEG-YNP(1)s increased, and aggregates precipitated after less than 1 h in phosphate buffer saline (PBS). In contrast, the size did not change at all in the case of PEG-YNP(b)s and the dispersion in PBS was stable for over 1 week. PEG-YNP(b)s also showed high erosion resistance under acidic conditions. The multiple coordinated PVBP segment of the block copolymer on the YNP surface plays a substantial role in improving such dispersion stability. The excellent dispersion stability and strong NIR luminescence of the obtained PEG-YNP(b)s were also confirmed in fetal bovine serum (FBS) solution over 1 week. Furthermore, in vivo NIR imaging of live mice was performed, and the 1550 nm NIR emission of PEG-YNP(b)s from the organ of live mice was confirmed without dissection.A novel poly(ethylene glycol) (PEG)-based block copolymer possessing a 4-vinylbenzylphosphonate repeating unit in another segment (PEG-block-poly(4-vinylbenzylphosphonate)) (PEG-b-PVBP) was designed and successfully synthesized. As a control, an end-functionalized PEG possessing a mono-phosphonate group (PEG-PO3H2) was also synthesized. The surface of near-infrared (NIR) phosphors (i.e., ytterbium (Yb) and erbium (Er) ion-codoped Y2O3 nanoparticles (YNPs)) were modified with PEG-b-PVBP (PEG-YNP(b)s) and PEG-PO3H2 (PEG-YNP(1)s). The adsorption of PEG-b-PVBP and PEG-PO3H2 was estimated by Fourier transform infrared (FT-IR) measurements and thermal gravimetric analysis (TGA). The physicochemical characteristics of the obtained YNP samples were analyzed by ζ-potential and dynamic light scattering (DLS) measurements. The ζ-potentials of YNPs modified by these polymers were close to zero, indicating the effective coverage of the YNP surface by our new PEG derivatives. However, the dispersion stability of the PEGylated YNPs was strongly affected by the structure of the PEG terminus. The average diameter of the PEG-YNP(1)s increased, and aggregates precipitated after less than 1 h in phosphate buffer saline (PBS). In contrast, the size did not change at all in the case of PEG-YNP(b)s and the dispersion in PBS was stable for over 1 week. PEG-YNP(b)s also showed high erosion resistance under acidic conditions. The multiple coordinated PVBP segment of the block copolymer on the YNP surface plays a substantial role in improving such dispersion stability. The excellent dispersion stability and strong NIR luminescence of the obtained PEG-YNP(b)s were also confirmed in fetal bovine serum (FBS) solution over 1 week. Furthermore, in vivo NIR imaging of live mice was performed, and the 1550 nm NIR emission of PEG-YNP(b)s from the organ of live mice was confirmed without dissection. Electronic supplementary information (ESI) available: 1H-NMR spectra of PEG-b-PCMS, PEG-b-PDEVBP and PEG-b-PVBP, 31P-NMR spectra of PEG-b-PDEVBP and PEG-b-PVBP, schematic representation of PEG-PO3H2 synthesis, 1H-NMR spectra of PEG-PO3Et2 and PEG-PO3H2, FT-IR spectra of YNP samples, PEG brush density on the YNP surface, and size distribution of YNP samples under acidic conditions are described. See DOI: 10.1039/c1nr10466g

Dielectric and piezoelectric properties of percolative three-phase piezoelectric polymer composites

NASA Astrophysics Data System (ADS)

Sundar, Udhay

Three-phase piezoelectric bulk composites were fabricated using a mix and cast method. The composites were comprised of lead zirconate titanate (PZT), aluminum (Al) and an epoxy matrix. The volume fraction of the PZT and Al were varied from 0.1 to 0.3 and 0.0 to 0.17, respectively. The influences of three entities on piezoelectric and dielectric properties: inclusion of an electrically conductive filler (Al), poling process (contact and Corona) and Al surface treatment, were observed. The piezoelectric strain coefficient, d33, effective dielectric constant, epsilon r, capacitance, C, and resistivity were measured and compared according to poling process, volume fraction of constituent phases and Al surface treatment. The maximum values of d33 were 3.475 and 1.0 pC/N for Corona and contact poled samples respectively, for samples with volume fractions of 0.40 and 0.13 of PZT and Al (surface treated) respectively. Also, the maximum dielectric constant for the surface treated Al samples was 411 for volume fractions of 0.40 and 0.13 for PZT and Al respectively. The percolation threshold was observed to occur at an Al volume fraction of 0.13. The composites achieved a percolated state for Al volume fractions >0.13 for both contact and corona poled samples. In addition, a comparative time study was conducted to examine the influence of surface treatment processing time of Al particles. The effectiveness of the surface treatment, sample morphology and composition was observed with the aid of SEM and EDS images. These images were correlated with piezoelectric and dielectric properties. PZT-epoxy-aluminum thick films (200 mum) were also fabricated using a two-step spin coat deposition and annealing method. The PZT volume fraction were varied from 0.2, 0.3 and 0.4, wherein the Aluminum volume fraction was varied from 0.1 to 0.17 for each PZT volume fraction, respectively. The two-step process included spin coating the first layer at 500 RPM for 30 seconds, and the second layer at 1000 RPM for 1 minute. The piezoelectric strain coefficients d33 and d31, capacitance and the dielectric constant were measured, and were studied as a function of Aluminum volume fraction.

PEG and mPEG-anthracene induce DNA condensation and particle formation.

PubMed

Froehlich, E; Mandeville, J S; Arnold, D; Kreplak, L; Tajmir-Riahi, H A

2011-08-18

In this study, we investigated the binding of DNA with poly(ethylene glycol) (PEG) of different sizes and compositions such as PEG 3350, PEG 6000, and mPEG-anthracene in aqueous solution at physiological conditions. The effects of size and composition on DNA aggregation and condensation as well as conformation were determined using Fourier transform infrared (FTIR), UV-visible, CD, fluorescence spectroscopic methods and atomic force microscopy (AFM). Structural analysis showed moderate complex formation for PEG 3350 and PEG 6000 and weaker interaction for mPE-anthracene-DNA adducts with both hydrophilic and hydrophobic contacts. The order of ± stability of the complexes formed is K(PEG 6000) = 1.5 (±0.4) × 10(4) M(-1) > K(PEG 3350) = 7.9 (±1) × 10(3) M(-1) > K(m(PEG-anthracene))= 3.6 (±0.8) × 10(3) M(-1) with nearly 1 bound PEG molecule per DNA. No B-DNA conformational changes were observed, while DNA condensation and particle formation occurred at high PEG concentration.

40 CFR 63.4730 - What records must I keep?

Code of Federal Regulations, 2010 CFR

2010-07-01

... to determine the mass fraction of organic HAP and density for each coating, thinner, and cleaning material and the volume fraction of coating solids for each coating. If you conducted testing to determine mass fraction of organic HAP, density, or volume fraction of coating solids, you must keep a copy of...

Effect of PEG and mPEG-anthracene on tRNA aggregation and particle formation.

PubMed

Froehlich, E; Mandeville, J S; Arnold, D; Kreplak, L; Tajmir-Riahi, H A

2012-01-09

Poly(ethylene glycol) (PEG) and its derivatives are synthetic polymers with major applications in gene and drug delivery systems. Synthetic polymers are also used to transport miRNA and siRNA in vitro. We studied the interaction of tRNA with several PEGs of different compositions, such as PEG 3350, PEG 6000, and mPEG-anthracene under physiological conditions. FTIR, UV-visible, CD, and fluorescence spectroscopic methods as well as atomic force microscopy (AFM) were used to analyze the PEG binding mode, the binding constant, and the effects of polymer complexation on tRNA stability, aggregation, and particle formation. Structural analysis showed that PEG-tRNA interaction occurs via RNA bases and the backbone phosphate group with both hydrophilic and hydrophobic contacts. The overall binding constants of K(PEG 3350-tRNA)= 1.9 (±0.5) × 10(4) M(-1), K(PEG 6000-tRNA) = 8.9 (±1) × 10(4) M(-1), and K(mPEG-anthracene)= 1.2 (±0.40) × 10(3) M(-1) show stronger polymer-RNA complexation by PEG 6000 and by PEG 3350 than the mPEG-anthracene. AFM imaging showed that PEG complexes contain on average one tRNA with PEG 3350, five tRNA with PEG 6000, and ten tRNA molecules with mPEG-anthracene. tRNA aggregation and particle formation occurred at high polymer concentrations, whereas it remains in A-family structure.

Efficacy and tolerability of peg-only laxative on faecal impaction and chronic constipation in children. A controlled double blind randomized study vs a standard peg-electrolyte laxative

PubMed Central

2012-01-01

Background PEG-based laxatives are considered today the gold standard for the treatment of constipation in children. PEG formulations differ in terms of composition of inactive ingredients which may have an impact on acceptance, compliance and adherence to treatment. We therefore compared the efficacy, tolerability, acceptance and compliance of a new PEG-only formulation compared to a reference PEG-electrolyte (PEG-EL) formulation in resolving faecal impaction and in the treatment of chronic constipation. Methods Children aged 2–16 years with functional chronic constipation for at least 2 months were randomized to receive PEG-only 0.7 g/kg/day in 2 divided doses or 6.9 g PEG-EL 1–4 sachets according to age for 4 weeks. Children with faecal impaction were randomized to receive PEG-only 1.5/g/kg in 2 divided doses until resolution or for 6 days or PEG-EL with an initial dose of 4 sachets and increasing 2 sachets a day until resolution or for 7 days. Results Ninety-six children were randomized into the study. Five patients withdrew consent before starting treatment. Three children discontinued treatment for refusal due to bad taste of the product (1 PEG-only, 2 PEG-EL); 1 (PEG-EL) for an adverse effect (abdominal pain). Intent-to-treat analysis was carried out in 49 children in the PEG-only group and 42 in the PEG-EL group. No significant differences were observed between the two treatment groups at baseline. Adequate relief of constipation in terms of normalized frequency and painless defecation of soft stools was achieved in all patients in both groups. The number of stools/week was 9.2 ± 3.2 (mean ± SD) in the PEG-only group and 7.8 ± 2.4 in the PEG-EL group (p = 0.025); the number of days with stool was 22.4 ± 5.1 in the PEG-only group and 19.6 ± 7.2 in the PEG-EL group (p = 0.034). In the PEG-only group faecaloma resolution was observed in 5 children on the second day and in 2 children on the third day, while in the PEG-EL group it was observed in 2 children on the second day, in 3 children on the third day and in 1 child on the fifth day. Only 2 patients reported mild treatment-related adverse events: 1 child in the PEG-only group had diarrhoea and vomiting and 1 child in the PEG-EL group had abdominal pain requiring treatment discontinuation. The PEG-only preparation was better tolerated as shown by the lower frequency of nausea than in the PEG-EL group. In the PEG-only group, 96% of patients did not demonstrate any difficulties associated with treatment, as compared with 52% of patients in the PEG-EL group (p < 0.001). Also, the PEG-only formulation taste was better than that of PEG-EL (p < 0.001). The difference between the percentage of subjects who took > 80% of the prescribed dose was in favour of the PEG-only group (98% vs. 88%), though it did not reach a conventional statistical level (p = 0.062). Conclusion PEG-only was better tolerated and accepted than PEG-EL in children with chronic constipation. At the higher PEG doses recommended by the manufactures children in the PEG-only group had higher and more regular soft stool frequency than PEG-EL. Trial registration ClinicalTrials.gov: NCT01592734 PMID:23152962

Pharmacokinetic and Pharmacodynamic Properties of Calaspargase Pegol Escherichia coli L-Asparaginase in the Treatment of Patients With Acute Lymphoblastic Leukemia: Results From Children's Oncology Group Study AALL07P4

PubMed Central

Angiolillo, Anne L.; Schore, Reuven J.; Devidas, Meenakshi; Borowitz, Michael J.; Carroll, Andrew J.; Gastier-Foster, Julie M.; Heerema, Nyla A.; Keilani, Taha; Lane, Ashley R.; Loh, Mignon L.; Reaman, Gregory H.; Adamson, Peter C.; Wood, Brent; Wood, Charlotte; Zheng, Hao W.; Raetz, Elizabeth A.; Winick, Naomi J.; Carroll, William L.; Hunger, Stephen P.

2014-01-01

Purpose Asparaginase is a critical agent used to treat acute lymphoblastic leukemia (ALL). Pegaspargase (SS-PEG), a pegylated form of Escherichia coli L-asparaginase with a succinimidyl succinate (SS) linker, is the first-line asparaginase product used in Children's Oncology Group (COG) ALL trials. Calaspargase pegol (SC-PEG) replaces the SS linker in SS-PEG with a succinimidyl carbamate linker, creating a more stable molecule. COG AALL07P4 was designed to determine the pharmacokinetic and pharmacodynamic comparability of SC-PEG to SS-PEG in patients with newly diagnosed high-risk (HR) B-cell ALL. Patients and Methods A total of 165 evaluable patients were randomly assigned at a 2:1 ratio to receive SC-PEG at 2,100 (SC-PEG2100; n = 69) or 2,500 IU/m2 (SC-PEG2500; n = 42) versus SS-PEG 2,500 IU/m2 (SS-PEG2500; n = 54) as part of an otherwise identical chemotherapy regimen. The groups were similar demographically, except more female patients received SC-PEG2500. Results The mean half-life of plasma asparaginase activity for both SC-PEG doses was approximately 2.5× longer than that of SS-PEG2500. The total systemic exposure, as defined by induction area under the curve from time 0 to 25 days, was greater with SC-PEG2500 than with SS-PEG2500 or SC-PEG2100. The proportion of patients with plasma asparaginase activity ≥ 100 mIU/mL and ≥ 400 mIU/mL was higher in patients who received SC-PEG as compared with SS-PEG2500. After one dose of pegylated asparaginase on induction day 4, plasma asparagine was undetectable for 11 days for SS-PEG2500 and 18 days for both SC-PEG groups. Conclusion SC-PEG2500 achieves a significantly longer period of asparaginase activity above defined thresholds and asparagine depletion compared with SS-PEG2500 and has a comparable toxicity profile in children with HR B-cell ALL. PMID:25348002

Critical determinant of intestinal permeability and oral bioavailability of pegylated all trans-retinoic acid prodrug-based nanomicelles: Chain length of poly (ethylene glycol) corona.

PubMed

Li, Zhenbao; Han, Xiaopeng; Zhai, Yinglei; Lian, He; Zhang, Dong; Zhang, Wenjuan; Wang, Yongjun; He, Zhonggui; Liu, Zheng; Sun, Jin

2015-06-01

Pegylation method is widely used to prolong the blood circulation time of proteins and nanoparticles after intravenous administration, but the effect of surface poly (ethylene glycol) (PEG) chain length on oral absorption of the pegylated nanoparticles is poorly reported. The aim of our study was to investigate the influence of PEG corona chain length on membrane permeability and oral bioavailability of the amphiphilic pegylated prodrug-based nanomicelles, taking all trans-retinoic acid (ATRA) as a model drug. The amphiphilic ATRA-PEG conjugates were synthesized by esterification reaction between all trans-retinoic acid and mPEGs (mPEG500, mPEG1000, mPEG2000, and mPEG5000). The conjugates could self-assemble in aqueous medium to form nanomicelles by emulsion-solvent evaporation method. The resultant nanomicelles were in spherical shape with an average diameter of 13-20 nm. The drug loading efficiency of ATRA-PEG500, ATRA-PEG1000, ATRA-PEG2000, and ATRA-PEG5000 was about 38.4, 26.6, 13.1, and 5.68 wt%, respectively. With PEG chain length ranging from 500 to 5000, ATRA-PEG nanomicelles exhibited a bell shape of chemical stability in different pH buffers, intestinal homogenate and plasma. More importantly, they were all rapidly hydrolyzed into the parent drug in hepatic homogenate, with the half-time values being 0.3-0.4h. In comparison to ATRA solution and ATRA prodrug-based nanomicelles, ATRA-PEG1000 showed the highest intestinal permeability. After oral administration, ATRA-PEG2000 and ATRA-PEG5000 nanomicelles were not nearly absorbed, while the oral bioavailability of ATRA-PEG500 and ATRA-PEG1000 demonstrated about 1.2- and 2.0-fold higher than ATRA solution. Our results indicated that PEG1000 chain length of ATRA-PEG prodrug nanomicelles has the optimal oral bioavailability probably due to improved stability and balanced mucus penetration capability and cell binding, and that the PEG chain length on a surface of nanoparticles cannot exceed a key threshold with the purpose of enhancement in oral bioavailability. Copyright © 2015. Published by Elsevier B.V.

Structural mass irregularities and fiber volume influence on morphology and mechanical properties of unsaturated polyester resin in matrix composites

PubMed Central

Ahmed, Khalil; Nasir, Muhammad; Fatima, Nasreen; Khan, Khalid M.; Zahra, Durey N.

2014-01-01

This paper presents the comparative results of a current study on unsaturated polyester resin (UPR) matrix composites processed by filament winding method, with cotton spun yarn of different mass irregularities and two different volume fractions. Physical and mechanical properties were measured, namely ultimate stress, stiffness, elongation%. The mechanical properties of the composites increased significantly with the increase in the fiber volume fraction in agreement with the Counto model. Mass irregularities in the yarn structure were quantitatively measured and visualized by scanning electron microscopy (SEM). Mass irregularities cause marked decrease in relative strength about 25% and 33% which increases with fiber volume fraction. Ultimate stress and stiffness increases with fiber volume fraction and is always higher for yarn with less mass irregularities. PMID:26644920

Polyethylene Glycol Polymers in Low Volume Resuscitation

DTIC Science & Technology

2017-10-01

peripheral vascular disease and chronic heart failure, and space medicine. What as the impact on technology transfer? Technology transfer is a very...patterns were almost identical in volunteers and trauma patients. The significantly lower clot strength in blood diluted with 10% PEG-20k could be...lost in the US, compared to cancer (16%), heart disease (12%), and HIV (2%) (1). For all traumatic injuries, hemorrhagic shock is responsible for

Geometric confinement influences cellular mechanical properties I -- adhesion area dependence.

PubMed

Su, Judith; Jiang, Xingyu; Welsch, Roy; Whitesides, George M; So, Peter T C

2007-06-01

Interactions between the cell and the extracellular matrix regulate a variety of cellular properties and functions, including cellular rheology. In the present study of cellular adhesion, area was controlled by confining NIH 3T3 fibroblast cells to circular micropatterned islands of defined size. The shear moduli of cells adhering to islands of well defined geometry, as measured by magnetic microrheometry, was found to have a significantly lower variance than those of cells allowed to spread on unpatterned surfaces. We observe that the area of cellular adhesion influences shear modulus. Rheological measurements further indicate that cellular shear modulus is a biphasic function of cellular adhesion area with stiffness decreasing to a minimum value for intermediate areas of adhesion, and then increasing for cells on larger patterns. We propose a simple hypothesis: that the area of adhesion affects cellular rheological properties by regulating the structure of the actin cytoskeleton. To test this hypothesis, we quantified the volume fraction of polymerized actin in the cytosol by staining with fluorescent phalloidin and imaging using quantitative 3D microscopy. The polymerized actin volume fraction exhibited a similar biphasic dependence on adhesion area. Within the limits of our simplifying hypothesis, our experimental results permit an evaluation of the ability of established, micromechanical models to predict the cellular shear modulus based on polymerized actin volume fraction. We investigated the "tensegrity", "cellular-solids", and "biopolymer physics" models that have, respectively, a linear, quadratic, and 5/2 dependence on polymerized actin volume fraction. All three models predict that a biphasic trend in polymerized actin volume fraction as a function of adhesion area will result in a biphasic behavior in shear modulus. Our data favors a higher-order dependence on polymerized actin volume fraction. Increasingly better experimental agreement is observed for the tensegrity, the cellular solids, and the biopolymer models respectively. Alternatively if we postulate the existence of a critical actin volume fraction below which the shear modulus vanishes, the experimental data can be equivalently described by a model with an almost linear dependence on polymerized actin volume fraction; this observation supports a tensegrity model with a critical actin volume fraction.

Physicochemical Properties of Glycine-Based Ionic Liquid [QuatGly-OEt][EtOSO3] (2-Ethoxy-1-ethyl-1,1-dimethyl-2-oxoethanaminium ethyl sulfate) and Its Binary Mixtures with Poly(ethylene glycol) (Mw = 200) at Various Temperatures

PubMed Central

Wu, Tzi-Yi; Chen, Bor-Kuan; Hao, Lin; Lin, Yuan-Chung; Wang, H. Paul; Kuo, Chung-Wen; Sun, I-Wen

2011-01-01

This work includes specific basic characterization of synthesized glycine-based Ionic Liquid (IL) [QuatGly-OEt][EtOSO3] by NMR, elementary analysis and water content. Thermophysical properties such as density, ρ, viscosity, η, refractive index, n, and conductivity, κ, for the binary mixture of [QuatGly-OEt][EtOSO3] with poly(ethylene glycol) (PEG) [Mw = 200] are measured over the whole composition range. The temperature dependence of density and dynamic viscosity for neat [QuatGly-OEt][EtOSO3] and its binary mixture can be described by an empirical polynomial equation and by the Vogel-Tammann-Fucher (VTF) equation, respectively. The thermal expansion coefficient of the ILs is ascertained using the experimental density results, and the excess volume expansivity is evaluated. The negative values of excess molar volume for the mixture indicate the ion-dipole interactions and packing between IL and PEG oligomer. The results of binary excess property (VmE ) and deviations (Δη, Δxn, ΔΨn, ΔxR, and ΔΨR) are discussed in terms of molecular interactions and molecular structures in the binary mixture. PMID:22272102

Laser-Induced Incandescence Measurements in Low Gravity

NASA Technical Reports Server (NTRS)

VanderWal, R. L.

1997-01-01

A low-gravity environment offers advantages to investigations concerned with soot growth or flame radiation by eliminating of buoyancy-induced convection. Basic to each type of study is knowledge of spatially resolved soot volume fraction, (f(sub v). Laser-induced incandescence (LII) has emerged as a diagnostic for soot volume fraction determination because it possesses high temporal and spatial resolution, geometric versatility and high sensitivity. Implementation and system characterization of LII in a drop tower that provides 2.2 sec of low-gravity (micro)g) at the NASA Lewis Research Center are described here. Validation of LII for soot volume fraction determination in (micro)g is performed by comparison between soot volume fraction measurements obtained by light extinction [20] and LII in low-gravity for a 50/50 mixture (by volume) of 0 acetylene/nitrogen issuing into quiescent air. Quantitative soot volume fraction measurements within other laminar flames of ethane and propane and a turbulent diffusion flame in (micro)g via LII are also demonstrated. An analysis of LII images of a turbulent acetylene diffusion flame in 1-g and (micro)g is presented.

Crystalline polyoxometalate (POM)–polyethylene glycol (PEG) composites aimed as non-humidified intermediate-temperature proton conductors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsuboi, Masaki; Hibino, Mitsuhiro; Mizuno, Noritaka

2016-02-15

Crystalline polyoxometalate (POM)–polyethylene glycol (PEG) composites aimed as non-humidified intermediate-temperature proton conductors were synthesized and characterized by single crystal and powder XRD, solid state MASNMR, and TG-DTA measurements. Among the POM–PEG composites, Cs{sub 2.7}H{sub 0.3}[PW{sub 12}O{sub 40}]·1.2PEG1000 (CsHPW-PEG1000) possessed one-dimensional channels with diameters of ca. 6 and 8 Å, where PEG probably resided, and showed the best performance as a proton conductor (1.2×10{sup −5} S cm{sup −1} at 443 K). Proton conductivities of POM–PEG composites decreased by the increase in molecular weights of PEG (CsHPW-PEG12,000) or anion charges (CsHSiW-PEG1000). Variable contact time {sup 13}C-CP (cross polarization) MASNMR revealed that localmore » mobility (i.e., segmental motion) of PEG is related to the trends in proton conductivities. These results show that amount of acidic protons (H{sup +}) is not the primary factor in proton conduction and that segmental motion of PEG assists the proton hopping among POMs in the crystal lattice of POM–PEG composites. - Graphical abstract: Non-humidified intermediate-temperature proton conduction in crystalline polyoxometalate (POM)–polyethylene (PEG) composites are assisted by the segmental motion of PEG. - Highlights: • Crystalline polyoxometalate–polyethlene glycol (PEG) composites were synthesized. • CsHPW-PEG1000 possessed one-dimensional channels and showed the highest proton conductivity. • {sup 13}C CPMASNMR revealed that segmental motion of PEG is related to the proton conduction.« less

Effect of DSPE-PEG on compound action potential, injury potential and ion concentration following compression in ex vivo spinal cord.

PubMed

Wang, Aihua; Huo, Xiaolin; Zhang, Guanghao; Wang, Xiaochen; Zhang, Cheng; Wu, Changzhe; Rong, Wei; Xu, Jing; Song, Tao

2016-05-04

It has been shown that polyethylene glycol (PEG) can reseal membrane disruption on the spinal cord, but only high concentrations of PEG have been shown to have this effect. Therefore, the effect of PEG is somewhat limited, and it is necessary to investigate a new approach to repair spinal cord injury. This study assesses the ability of 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly (ethylene glycol)) 2000] (DSPE-PEG) to recover physiological function and attenuate the injury-induced influx of extracellular ions in ex vivo spinal cord injury. Isolated spinal cords were subjected to compression injury and treated with PEG or DSPE-PEG immediately after injury. The compound action potential (CAP) was recorded before and after injury to assess the functional recovery. Furthermore, injury potential, the difference in gap potentials before and after compression, and the concentration of intracellular ions were used to evaluate the effect of DSPE-PEG on reducing ion influx. Data showed that the injury potential and ion concentration of the untreated, PEG and DSPE-PEG group, without significant difference among them, are remarkably higher than those of the intact group. Moreover, the CAP recovery of the DSPE-PEG and PEG treated spinal cords was significantly greater than that of the untreated spinal cords. The level of CAP recovery in the DSPE-PEG and PEG treated groups was the same, but the concentration of DSPE-PEG used was much lower than the concentration of PEG. These results suggest that instant application of DSPE-PEG could effectively repair functional disturbance in SCI at a much lower concentration than PEG. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Quantification of skeletal fraction volume of a soil pit by means of photogrammetry

NASA Astrophysics Data System (ADS)

Baruck, Jasmin; Zieher, Thomas; Bremer, Magnus; Rutzinger, Martin; Geitner, Clemens

2015-04-01

The grain size distribution of a soil is a key parameter determining soil water behaviour, soil fertility and land use potential. It plays an important role in soil classification and allows drawing conclusions on landscape development as well as soil formation processes. However, fine soil material (i.e. particle diameter ≤2 mm) is usually documented more thoroughly than the skeletal fraction (i.e. particle diameter >2 mm). While fine soil material is commonly analysed in the laboratory in order to determine the soil type, the skeletal fraction is typically estimated in the field at the profile. For a more precise determination of the skeletal fraction other methods can be applied and combined. These methods can be volume-related (sampling rings, percussion coring tubes) or non-volume-related (sieve of spade excavation). In this study we present a framework for the quantification of skeletal fraction volumes of a soil pit by means of photogrammetry. As a first step 3D point clouds of both soil pit and skeletal grains were generated. Therefore all skeletal grains of the pit were spread out onto a plane, clean plastic sheet in the field and numerous digital photos were taken using a reflex camera. With the help of the open source tool VisualSFM (structure from motion) two scaled 3D point clouds were derived. As a second step the skeletal fraction point cloud was segmented by radiometric attributes in order to determine volumes of single skeletal grains. The comparison of the total skeletal fraction volume with the volume of the pit (closed by spline interpolation) yields an estimate of the volumetric proportion of skeletal grains. The presented framework therefore provides an objective reference value of skeletal fraction for the support of qualitative field records.

Synthesis of PEG-rich PLGA-PEG-PLGA for the PLGA-PEG-PLGA/laponite hydrogels with thermoresponsive sol-gel transitions

NASA Astrophysics Data System (ADS)

Tanimoto, Keishi; Maeda, Tomoki; Hotta, Atsushi

Poly (D,L-lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly (D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) possesses moderate biocompatibility originating from the relatively shorter PEG block in its polymeric molecule. For the maximum utilization of the highly biocompatible PEG block, the PEG block should be relatively longer, and thus the PEG/PLGA ratio, the molecular weight ratio of PEG and PLGA, should be higher. In addition, for the wider use of PLGA-PEG-PLGA in the biological fields, the aqueous PLGA-PEG-PLGA solution should transfer from sol to gel states in response to the increase in temperature. It was reported, however, through the previous researches, that the PLGA-PEG-PLGA solution with a high PEG/PLGA ratio (above 0.5) would not exhibit thermoresponsive sol-gel transitions. In this work, PLGA-PEG-PLGAs with higher PEG/PLGA ratios were synthesized and the laponite, an inorganic nanoparticle, was added to the solutions to realize the thermoresponsive sol-gel transition. It was found that the PLGA-PEG-PLGA with the high PEG/PLGA ratio of 3.0 could exhibit the thermoresponsive sol-gel transition by adding laponite at 1.25 weight percent. The physical characteristics of the gel were also studied by the dynamic mechanical analysis (DMA) This work was supported by a Grant-in-Aid for Scientific Research (A) (No. 15H02298 to A.H.) and a Grant-in-Aid for Research Activity Start-up (No.15H06586 to T.M.) from JSPS: KAKENHI\\x9D.

Safety Evaluation of Polyethylene Glycol (PEG) Compounds for Cosmetic Use

PubMed Central

Shin, Chan Young; Kim, Kyu-Bong

2015-01-01

Polyethylene glycols (PEGs) are products of condensed ethylene oxide and water that can have various derivatives and functions. Since many PEG types are hydrophilic, they are favorably used as penetration enhancers, especially in topical dermatological preparations. PEGs, together with their typically nonionic derivatives, are broadly utilized in cosmetic products as surfactants, emulsifiers, cleansing agents, humectants, and skin conditioners. The compounds studied in this review include PEG/PPG-17/6 copolymer, PEG-20 glyceryl triisostearate, PEG-40 hydrogenated castor oil, and PEG-60 hydrogenated castor oil. Overall, much of the data available in this review are on PEGylated oils (PEG-40 and PEG-60 hydrogenated castor oils), which were recommended as safe for use in cosmetics up to 100% concentration. Currently, PEG-20 glyceryl triisostearate and PEGylated oils are considered safe for cosmetic use according to the results of relevant studies. Additionally, PEG/PPG-17/6 copolymer should be further studied to ensure its safety as a cosmetic ingredient. PMID:26191379

40 CFR 63.3930 - What records must I keep?

Code of Federal Regulations, 2011 CFR

2011-07-01

... formulation data, or test data used to determine the mass fraction of organic HAP and density for each coating... coating. If you conducted testing to determine mass fraction of organic HAP, density, or volume fraction... rather than a record of the volume used. (e) A record of the mass fraction of organic HAP for each...

Avidin-biotin-PEG-CPA complexes as potential EPR-directed therapeutic protein carriers: preparation and characterization.

PubMed

Ke, Shan; Wright, John C; Kwon, Glen S

2007-01-01

Bovine carboxypeptidase A (CPA) conjugated with biotinylated poly(ethylene glycol) (PEG) has been synthesized and characterized in terms of stoichiometry and half-life of the avidin-biotin-PEG(s)-CPA complex. The half-lives for dissociation are 3.34 days for the avidin-biotin-PEG(3400)-CPA 1:1 complex, 3.65 days for the avidin-biotin-PEG(5000)-CPA 1:1 complex, 3.91 days for the avidin-biotin-PEG(3400)-CPA-PEG(2000) 1:1 complex, and 2.74 days for the avidin-biotin-PEG(5000)-CPA-PEG(2000) 1:1 complex. The slow dissociation demonstrates the stability of complexes using a PEGylated biotin terminus as a linker with avidin. The stoichiometry of the biotin-PEGylated CPA with avidin was determined by the 2,6-ANS method, and the results are consistent with measurements of the stoichiometry using size exclusion chromatography. The stoichiometries are 1:2 for the avidin-biotin-PEG(3400)-CPA complex and the avidin-biotin-PEG(3400)-CPA-PEG(2000) complex, 1:1 for the avidin-biotin-PEG(5000)-CPA complex, and 1:4 for the avidin-biotin-PEG(5000)-CPA-PEG(2000) complex. These findings stress both the importance of the length of a PEG chain as an appropriate spacer between the biotin terminus and a functional group, and the great potential of the avidin-biotin-PEGylated-protein complex as a therapeutic protein delivery system for solid tumor prodrug targeting.

Preparation of Polyamide-6 Submicrometer-Sized Spheres by In Situ Polymerization.

PubMed

Zhao, Xingke; Xia, Housheng; Fu, Xubing; Duan, Jianping; Yang, Guisheng

2015-11-01

Polyamide-6 (PA6) submicron-sized spheres are prepared by two steps: (1) anionic ring-opening polymerization of ε-caprolactam in the presence of poly(ethylene glycol)-block-poly-(propylene glycol)-block-poly(ethylene glycol)(PEG-b-PPG-b-PEG) and (2) separation of PA6 spheres by dissolving PEG-b-PPG-b-PEG from the prepared blends. The PA6 microspheres obtained are regular spherical, with diameter ranging from 200 nm to 2 μm and narrow size distribution, as confirmed by scanning electron microscopy. By comparison with PA6/PS and PA6/PEG systems, it is denominated that the PEG blocks in PEG-b-PPG-b-PEG can effectively reduce the surface tension of PA6 droplets and further decrease the diameter of the PA6 microspheres. The PPG block in PEG-b-PPG-b-PEG can prevent the PA6 droplets coalescing with each other, and isolated spherical particles can be obtained finally. The phase inversion of the PA6/PEG-b-PPG-b-PEG blends occurs at very low PEG-b-PPG-b-PEG content; the PEG-b-PPG-b-PEG phase can be removed by water easily. The whole experiment can be finished in a short time (approximately in half an hour) without using any organic solvents; it is an efficient strategy for the preparation of submicron-sized PA6 microspheres. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

TRAQUEOESOPHAGEAL FISTULA PATIENTS FED THROUGH PERCUTANEOUS ENDOSCOPIC GASTROSTOMY/GASTROJEJUNOSTOMY: NUTRITIONAL STATUS AND CLINICAL OUTCOME.

PubMed

Santos, Carla Adriana; Pereira, Marta; Martins, Vera Santos; Fonseca, Jorge

2015-08-01

tracheoesophageal fistula (TEF) may result from cancer or mechanical ventilation. Endoscopic Gastrostomy or Gastrojejunostomy (PEG/PEG-J) is used for nutritional support. in TEF-patients, evaluating nutritional status when PEG is performed, safety of PEG/PEG-J and clinical outcome. from the files of PEG/PEG-J feed TEF-patients we collected: clinical data, Body Mass Index, albumin, transferrin and cholesterol when gastrostomy was performed, and clinical outcome globally and according with the TEF cause: Group 1: complication of mechanical ventilation, Group 2: cancer. twelve patients, 18-91 years (median: 53), 11 PEG, one PEG-J: six complications of ventilation (neurological diseases), 6 cancers. Mean period from TEF diagnosis until gastrostomy: 2 months in Group 1, 10 months in Group 2. In the day of the gastrostomy, patients presented with malnutrition parameters, most strikingly in the cancer group. Group 1: died a single patient, 3 closed the TEF, resuming oral intake, 2 are still PEG-feed. All cancer patients died (7 months after gastrostomy). One needed a jejunal extension to create a PEG-J. No more complications. PEG/PEG-J was safe in TEF-patients, but cancer patients underwent gastrostomy too late. In TEF-patients, PEG/PEG-J should be considered in a regular basis, earlier in the disease evolution, before established malnutrition. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Influence of primary α-phase volume fraction on the mechanical properties of Ti-6Al-4V alloy at different strain rates and temperatures

NASA Astrophysics Data System (ADS)

Ren, Yu; Zhou, Shimeng; Luo, Wenbo; Xue, Zhiyong; Zhang, Yajing

2018-03-01

Bimodal microstructures with primary α-phase volume fractions ranging from 14.3% to 57.1% were gained in Ti-6Al-4V (Ti-64) alloy through annealed in two-phase region at various temperatures below the β-transus point. Then the influence of the primary α-phase volume fraction on the mechanical properties of Ti-64 were studied. The results show that, at room temperature and a strain rate of 10‑3 s‑1, the yield stress decreases but the fracture strain augments with added primary α-phase volume fraction. The equiaxed primary α-phase possesses stronger ability to coordinate plastic deformation, leading to the improvement of the ductile as well as degradation of the strength of Ti-64 with higher primary α-phase volume fraction. As the temperature goes up to 473 K, the quasi-static yield stress and ultimate strength decrease first and then increase with the incremental primary α-phase volume fraction, due to the interaction between the work hardening and the softening caused by the DRX and the growth of the primary α-phase. At room temperature and a strain rate of 3×103 s‑1, the varying pattern of strength with the primary α-phase volume fraction resembles that at a quasi-static strain rate. However, the flow stress significantly increases but the strain-hardening rate decreases compared to those at quasi-static strain rate due to the competition between the strain rate hardening and the thermal softening during dynamic compression process.

Long-term aging behaviors in a model soft colloidal system.

PubMed

Li, Qi; Peng, Xiaoguang; McKenna, Gregory B

2017-02-15

Colloidal and molecular systems share similar behaviors near to the glass transition volume fraction or temperature. Here, aging behaviors after volume fraction up-jump (induced by performing temperature down-jumps) conditions for a PS-PNIPAM/AA soft colloidal system were investigated using light scattering (diffusing wave spectroscopy, DWS). Both aging responses and equilibrium dynamics were investigated. For the aging responses, long-term experiments (100 000 s) were performed, and both equilibrium and non-equilibrium behaviors of the system were obtained. In the equilibrium state, as effective volume fraction increases (or temperature decreases), the colloidal dispersion displays a transition from the liquid to a glassy state. The equilibrium α-relaxation dynamics strongly depend on both the effective volume fraction and the initial mass concentration for the studied colloidal systems. Compared with prior results from our lab [X. Di, X. Peng and G. B. McKenna, J. Chem. Phys., 2014, 140, 054903], the effective volume fractions investigated spanned a wider range, to deeper into the glassy domain. The results show that the α-relaxation time τ α of the samples aged into equilibrium deviate from the classical Vogel-Fulcher-Tammann (VFT)-type expectations and the super-Arrhenius signature disappears above the glass transition volume fraction. The non-equilibrium aging response shows that the time for the structural evolution into equilibrium and the α-relaxation time are decoupled. The DWS investigation of the aging behavior after different volume fraction jumps reveals a different non-equilibrium or aging behavior for the considered colloidal systems compared with either molecular glasses or the macroscopic rheology of a similar colloidal dispersions.

Density-tunable conjugation of cyclic RGD ligands with polyion complex vesicles for the neovascular imaging of orthotopic glioblastomas

NASA Astrophysics Data System (ADS)

Kawamura, Wataru; Miura, Yutaka; Kokuryo, Daisuke; Toh, Kazuko; Yamada, Naoki; Nomoto, Takahiro; Matsumoto, Yu; Sueyoshi, Daiki; Liu, Xueying; Aoki, Ichio; Kano, Mitsunobu R.; Nishiyama, Nobuhiro; Saga, Tsuneo; Kishimura, Akihiro; Kataoka, Kazunori

2015-06-01

Introduction of ligands into 100 nm scaled hollow capsules has great potential for diagnostic and therapeutic applications in drug delivery systems. Polyethylene glycol-conjugated (PEGylated) polyion complex vesicles (PICsomes) are promising hollow nano-capsules that can survive for long periods in the blood circulation and can be used to deliver water-soluble macromolecules to target tissues. In this study, cyclic RGD (cRGD) peptide, which is specifically recognized by αVβ3 and αvβ5 integrins that are expressed at high levels in the neovascular system, was conjugated onto the distal end of PEG strands on PICsomes for active neovascular targeting. Density-tunable cRGD-conjugation was achieved using PICsomes with definite fraction of end-functionalized PEG, to substitute 20, 40, and 100% of PEG distal end of the PICsomes to cRGD moieties. Compared with control-PICsomes without cRGD, cRGD-PICsomes exhibited increased uptake into human umbilical vein endothelial cells. Intravital confocal laser scanning microscopy revealed that the 40%-cRGD-PICsomes accumulated mainly in the tumor neovasculature and remained in the perivascular region even after 24 h. Furthermore, we prepared superparamagnetic iron oxide (SPIO)-loaded cRGD-PICsomes for magnetic resonance imaging (MRI) and successfully visualized the neovasculature in an orthotopic glioblastoma model, which suggests that SPIO-loaded cRGD-PICsomes might be useful as a MRI contrast reagent for imaging of the tumor microenvironment, including neovascular regions that overexpress αVβ3 integrins.

Preventive antitumor activity against hepatocellular carcinoma (HCC) induced by immunization with fusions of dendritic cells and HCC cells in mice.

PubMed

Homma, S; Toda, G; Gong, J; Kufe, D; Ohno, T

2001-11-01

The prevention of recurrence of hepatocellular carcinoma (HCC) after treatment is very important for improvement of the prognosis of HCC patients. Dendritic cells (DCs) are potent antigen-presenting cells that can prime naive T cells to induce a primary immune response. We attempted to induce preventive antitumor immunity against HCC by immunizing BALB/c mice with fusions of DCs and HCC cells. Murine bone marrow-derived DCs and a murine HCC cell line. BNL cells, were fused by treatment with 50% polyethyleneglvcol (PEG). Fusion efficacy was assessed by the analysis of fusions of BNL cells stained with red fluorescent dye and DCs stained with green fluorescent dye. Mice injected intravenously with DC/BNL fusions were challenged by BNL cell inoculation. About 30% of the PEG-treated non-adherent cells with both fluorescences were considered to be fusion cells. The cell fraction of DC/BNL fusions showed phenotypes of DCs, MHC class II, CD80, CD86, and intercellular adhesion molecule (ICAM)-1, which were not expressed on BNL cells. Mice immunized with the fusions were protected against the inoculation of BNL tumor cells, whereas injection with a mixture of DCs and BNL cells not treated with PEG did not provide significant resistance against BNL cell inoculation. Splenocytes from DC/BNL fusion-immunized mice showed lytic activity against BNL cells. These results demonstrate that immunization with fusions of DCs and HCC cells is capable of inducing preventive antitumor immunity against HCC.

Synthesis and Characterization of Elastin-Mimetic Hybrid Polymers with Multiblock, Alternating Molecular Architecture and Elastomeric Properties

PubMed Central

Grieshaber, Sarah E.; Farran, Alexandra J. E.; Lin-Gibson, Sheng; Kiick, Kristi L.; Jia, Xinqiao

2009-01-01

We are interested in developing elastin–mimetic hybrid polymers (EMHPs) that capture the multiblock molecular architecture of tropoelastin as well as the remarkable elasticity of mature elastin. In this study, multiblock EMHPs containing flexible synthetic segments based on poly(ethylene glycol) (PEG) alternating with alanine-rich, lysine-containing peptides were synthesized by step-growth polymerization using α,ω-azido-PEG and alkyne-terminated AKA3KA (K = lysine, A = alanine) peptide, employing orthogonal click chemistry. The resulting EMHPs contain an estimated three to five repeats of PEG and AKA3KA and have an average molecular weight of 34 kDa. While the peptide alone exhibited α-helical structures at high pH, the fractional helicity for EMHPs was reduced. Covalent cross-linking of EMHPs with hexamethylene diisocyanate (HMDI) through the lysine residue in the peptide domain afforded an elastomeric hydrogel (xEMHP) with a compressive modulus of 0.12 MPa when hydrated. The mechanical properties of xEMHP are comparable to a commercial polyurethane elastomer (Tecoflex SG80A) under the same conditions. In vitro toxicity studies showed that while the soluble EMHPs inhibited the growth of primary porcine vocal fold fibroblasts (PVFFs) at concentrations ≥0.2 mg/mL, the cross-linked hybrid elastomers did not leach out any toxic reagents and allowed PVFFs to grow and proliferate normally. The hybrid and modular approach provides a new strategy for developing elastomeric scaffolds for tissue engineering. PMID:19763157

Application of microchip CGE for the analysis of PEG-modified recombinant human granulocyte-colony stimulating factors.

PubMed

Park, Eun Ji; Lee, Kyung Soo; Lee, Kang Choon; Na, Dong Hee

2010-11-01

The purpose of this study was to evaluate the microchip CGE (MCGE) for the analysis of PEG-modified granulocyte-colony stimulating factor (PEG-G-CSF) prepared with PEG-aldehydes. The unmodified and PEG-modified G-CSFs were analyzed by Protein 80 and 230 Labchips on the Agilent 2100 Bioanalyzer. The MCGE allowed size-based separation and quantitation of PEG-G-CSF. The Protein 80 Labchip was useful for PEG-5K-G-CSF, while the Protein 230 Labchip was more suitable for PEG-20K-G-CSF. The MCGE was also used to monitor a search for optimal PEG-modification (PEGylation) conditions to produce mono-PEG-G-CSF. This study demonstrates the usefulness of MCGE for monitoring and optimizing the PEGylation of G-CSF with the advantages of speed, minimal sample consumption, and automatic quantitation.

Bisacodyl plus split 2-L polyethylene glycol-citrate-simethicone improves quality of bowel preparation before screening colonoscopy.

PubMed

Valiante, Flavio; Bellumat, Angelo; De Bona, Manuela; De Boni, Michele

2013-09-07

To compare the bowel cleansing efficacy, tolerability and acceptability of split 2-L polyethylene glycol (PEG)-citrate-simethicone (PEG-CS) plus bisacodyl (BIS) vs 4-L PEG for fecal occult blood test-positive screening colonoscopy. This was a randomised, observer-blind comparative study. Two hundred and sixty-four subjects underwent screening colonoscopy (mean age 62.5 ± 7.4 years, male 61.7%). The primary objective of the study was to compare the bowel cleansing efficacy of the two preparations. BIS plus PEG-CS: 3 tablets of 5-mg BIS at 16:00, PEG-CS 1-L at 19:00 and 1-L at 7:00, 4-L PEG: 3-L at 17:00, and 1-L at 7:00. Colonoscopy was carried out after 11:00, at least 3 h after the completion of bowel preparation. Bowel cleansing was evaluated using the Harefield Cleansing Scale. Bowel preparation was successful for 92.8% of subjects in the PEG-CS group and for 92.1% of subjects in the 4-L PEG (RR = 1.01; 95%CI: 0.94-1.08). BIS + PEG-CS was better tolerated than 4-L PEG. A greater rate of patients in the BIS + PEG-CS group had no difficulty and/or were willing to repeat the same preparation compared to split-dose 4-L PEG group. Subjects in the BIS + PEG-CS group rated the prep as good or satisfactory in 90.6% as compared to 77% in the 4-L PEG (P = 0.003). Subjects receiving BIS + PEG-CS stated they fully adhered to instructions drinking all the 2-L solution in 97.1% compared with 87.3% in the 4-L PEG (P = 0.003). BIS plus split 2-L PEG-CS was as effective as but better tolerated and accepted than split 4-L PEG for screening colonoscopy. This new procedure may increase the positive attitude and participation to colorectal cancer screening colonoscopy.

Preparation of PEG-conjugated fullerene containing Gd3+ ions for photodynamic therapy.

PubMed

Liu, Jian; Ohta, Shin-Ichi; Sonoda, Akinaga; Yamada, Masatoshi; Yamamoto, Masaya; Nitta, Norihisa; Murata, Kiyoshi; Tabata, Yasuhiko

2007-01-22

A novel photosensitizer with magnetic resonance imaging (MRI) activity was designed from fullerene (C(60)) for efficient photodynamic therapy (PDT) of tumor. After chemical conjugation of polyethylene glycol (PEG) to C(60) (C(60)-PEG), diethylenetriaminepentaacetic acid (DTPA) was subsequently introduced to the terminal group of PEG to prepare PEG-conjugated C(60) (C(60)-PEG-DTPA). The C(60)-PEG-DTPA was mixed with gadolinium acetate solution to obtain Gd(3+)-chelated C(60)-PEG (C(60)-PEG-Gd). Following intravenous injection of C(60)-PEG-Gd into tumor-bearing mice, the PDT anti-tumor effect and the MRI tumor imaging were evaluated. The similar O(2)(*-)generation was observed with or without Gd(3+) chelation upon light irradiation. Both of the C(60)-PEG-Gd and Magnevist(R) aqueous solutions exhibited a similar MRI activity. When intravenously injected into tumor-bearing mice, the C(60)-PEG-Gd maintained an enhanced MRI signal at the tumor tissue for a longer time period than Magnevist(R). Injection of C(60)-PEG-Gd plus light irradiation showed significant tumor PDT effect although the effect depended on the timing of light irradiation. The PDT efficacy of C(60)-PEG-Gd was observed at the time when the tumor accumulation was detected by the enhanced intensity of MRI signal. This therapeutic and diagnostic hybrid system is a promising tool to enhance the PDT efficacy for tumor.

Computational Characterization of Impact Induced Multi-Scale Dissipation in Reactive Solid Composites

DTIC Science & Technology

2016-07-01

Predicted variation in (a) hot-spot number density , (b) hot-spot volume fraction, and (c) hot-spot specific surface area for each ensemble with piston speed...packing density , characterized by its effective solid volume fraction φs,0, affects hot-spot statistics for pressure dominated waves corresponding to...distribution in solid volume fraction within each ensemble was nearly Gaussian, and its standard deviation decreased with increasing density . Analysis of

Lamb Wave Assessment of Fiber Volume Fraction in Composites

NASA Technical Reports Server (NTRS)

Seale, Michael D.; Smith, Barry T.; Prosser, W. H.; Zalameda, Joseph N.

1998-01-01

Among the various techniques available, ultrasonic Lamb waves offer a convenient method of examining composite materials. Since the Lamb wave velocity depends on the elastic properties of a material, an effective tool exists to evaluate composites by measuring the velocity of these waves. Lamb waves can propagate over long distances and are sensitive to the desired in-plane elastic properties of the material. This paper discusses a study in which Lamb waves were used to examine fiber volume fraction variations of approximately 0.40-0.70 in composites. The Lamb wave measurements were compared to fiber volume fractions obtained from acid digestion tests. Additionally, a model to predict the fiber volume fraction from Lamb wave velocity values was evaluated.

Estimation of the fractional coverage of rainfall in climate models

NASA Technical Reports Server (NTRS)

Eltahir, E. A. B.; Bras, R. L.

1993-01-01

The fraction of the grid cell area covered by rainfall, mu, is an essential parameter in descriptions of land surface hydrology in climate models. A simple procedure is presented for estimating this fraction, based on extensive observations of storm areas and rainfall volumes. Storm area and rainfall volume are often linearly related; this relation can be used to compute the storm area from the volume of rainfall simulated by a climate model. A formula is developed for computing mu, which describes the dependence of the fractional coverage of rainfall on the season of the year, the geographical region, rainfall volume, and the spatial and temporal resolution of the model. The new formula is applied in computing mu over the Amazon region. Significant temporal variability in the fractional coverage of rainfall is demonstrated. The implications of this variability for the modeling of land surface hydrology in climate models are discussed.

Naval War College Review. Volume 68, Number 2, Spring 2015

DTIC Science & Technology

2015-01-01

economy the government established a currency board that pegged the Bulgarian unit of currency, the lev, to the German mark� The banking sector was...Consider an attack during an armed conflict on the enemy’s banking , taxation, government pension, or airline reservations systems� Critics of a restrictive...targets cannot be struck kinetically in a fashion that would generate the same effects as cyber attacks� Consider the banking system� While kinetic

Draft Environmental Impact Statement. MX Deployment Area Selection & Land Withdrawal/Acquisition. Volume I. Program Overview.

DTIC Science & Technology

1980-12-01

loWaeSiptlAt ppovarision ’a- fcna Slf ate ngmn As it lIeh Solido waatdooa Waste Ac..13 065k, Sec. 4-.e.Sq Sil..d i.t ltgt. PegsCA a. P.q perinn ,ca Prtert...NATURAI ENVIPONMENT r -1--RESOURCE WATE KGOR. RESOURCE: ATTE IBUTE ater Iurfac- wauE’ Location (ma: Leve Runoff acr -- ft Sediment load (tons) "C a

Near-infrared (1550 nm) in vivo bioimaging based on rare-earth doped ceramic nanophosphors modified with PEG-b-poly(4-vinylbenzylphosphonate).

PubMed

Kamimura, Masao; Kanayama, Naoki; Tokuzen, Kimikazu; Soga, Kohei; Nagasaki, Yukio

2011-09-01

A novel poly(ethylene glycol) (PEG)-based block copolymer possessing a 4-vinylbenzylphosphonate repeating unit in another segment (PEG-block-poly(4-vinylbenzylphosphonate)) (PEG-b-PVBP) was designed and successfully synthesized. As a control, an end-functionalized PEG possessing a mono-phosphonate group (PEG-PO(3)H(2)) was also synthesized. The surface of near-infrared (NIR) phosphors (i.e., ytterbium (Yb) and erbium (Er) ion-codoped Y(2)O(3) nanoparticles (YNPs)) were modified with PEG-b-PVBP (PEG-YNP(b)s) and PEG-PO(3)H(2) (PEG-YNP(1)s). The adsorption of PEG-b-PVBP and PEG-PO(3)H(2) was estimated by Fourier transform infrared (FT-IR) measurements and thermal gravimetric analysis (TGA). The physicochemical characteristics of the obtained YNP samples were analyzed by ζ-potential and dynamic light scattering (DLS) measurements. The ζ-potentials of YNPs modified by these polymers were close to zero, indicating the effective coverage of the YNP surface by our new PEG derivatives. However, the dispersion stability of the PEGylated YNPs was strongly affected by the structure of the PEG terminus. The average diameter of the PEG-YNP(1)s increased, and aggregates precipitated after less than 1 h in phosphate buffer saline (PBS). In contrast, the size did not change at all in the case of PEG-YNP(b)s and the dispersion in PBS was stable for over 1 week. PEG-YNP(b)s also showed high erosion resistance under acidic conditions. The multiple coordinated PVBP segment of the block copolymer on the YNP surface plays a substantial role in improving such dispersion stability. The excellent dispersion stability and strong NIR luminescence of the obtained PEG-YNP(b)s were also confirmed in fetal bovine serum (FBS) solution over 1 week. Furthermore, in vivo NIR imaging of live mice was performed, and the 1550 nm NIR emission of PEG-YNP(b)s from the organ of live mice was confirmed without dissection.

Analysis of peg formation in cucumber seedlings grown on clinostats and in a microgravity (space) environment.

PubMed

Link, B M; Cosgrove, D J

1999-12-01

In young cucumber seedlings, the peg is a polar out-growth of tissue that functions by snagging the seed coat, thereby freeing the cotyledons. Previous studies have indicated that peg formation is gravity dependent. In this study we analyzed peg formation in cucumber seedlings (Cucumis sativus L. cv Burpee Hybrid II) grown under conditions of normal gravity, microgravity, and simulated microgravity (clinostat rotation). Seeds were germinated on the ground, in clinostats and on board the space shuttle (STS 95) for 1-2 days, frozen and subsequently examined for their stage of development, degree of hook formation, number of pegs formed, and peg morphology. The frequency of peg formation in space grown seedlings was found to be nearly identical to that of clinostat grown seedlings and to differ from that of seedlings germinated under normal gravity only in a minority of cases; approximately 6% of the seedlings formed two pegs and nearly 2% of the seedlings lacked pegs, whereas such abnormalities did not occur in ground controls. The degree of hook formation was found to be less pronounced for space grown seedlings, compared to clinostat grown seedlings, indicating a greater degree of decoupling between peg formation and hook formation in space. Nonetheless, in all seedlings having single pegs and a hook, the peg was found to be positioned correctly on the inside of the hook, showing that there is coordinate development even in microgravity environments. Peg morphologies were altered in space grown samples, with the pegs having a blunt appearance and many pegs showing alterations in expansion, with the peg extending out over the edges of the seed coat and downwards. These phenotypes were not observed in clinostat or ground grown seedlings.

Analysis of peg formation in cucumber seedlings grown on clinostats and in a microgravity (space) environment

NASA Technical Reports Server (NTRS)

Link, B. M.; Cosgrove, D. J.

1999-01-01

In young cucumber seedlings, the peg is a polar out-growth of tissue that functions by snagging the seed coat, thereby freeing the cotyledons. Previous studies have indicated that peg formation is gravity dependent. In this study we analyzed peg formation in cucumber seedlings (Cucumis sativus L. cv Burpee Hybrid II) grown under conditions of normal gravity, microgravity, and simulated microgravity (clinostat rotation). Seeds were germinated on the ground, in clinostats and on board the space shuttle (STS 95) for 1-2 days, frozen and subsequently examined for their stage of development, degree of hook formation, number of pegs formed, and peg morphology. The frequency of peg formation in space grown seedlings was found to be nearly identical to that of clinostat grown seedlings and to differ from that of seedlings germinated under normal gravity only in a minority of cases; approximately 6% of the seedlings formed two pegs and nearly 2% of the seedlings lacked pegs, whereas such abnormalities did not occur in ground controls. The degree of hook formation was found to be less pronounced for space grown seedlings, compared to clinostat grown seedlings, indicating a greater degree of decoupling between peg formation and hook formation in space. Nonetheless, in all seedlings having single pegs and a hook, the peg was found to be positioned correctly on the inside of the hook, showing that there is coordinate development even in microgravity environments. Peg morphologies were altered in space grown samples, with the pegs having a blunt appearance and many pegs showing alterations in expansion, with the peg extending out over the edges of the seed coat and downwards. These phenotypes were not observed in clinostat or ground grown seedlings.

Post-modification of preformed liposomes with novel non-phospholipid poly(ethylene glycol)-conjugated hexadecylcarbamoylmethyl hexadecanoic acid for enhanced circulation persistence in vivo

PubMed Central

Nag, Okhil K; Yadav, Vivek R; Hedrick, Andria; Awasthi, Vibhudutta

2013-01-01

We report synthesis and characterization of a novel PEG2000-conjugated hexadecylcarbamoylmethyl hexadecanoate (HDAS-PEG) as a PEG-phospholipid substitute for enhancing circulation persistence of liposomes. HDAS-PEG showed critical micelle concentration of 4.25 μM. We used post-insertion technique to introduce HDAS-PEG in outer lipid layer of the preformed liposomes. The presence of surface HDAS-PEG was confirmed by altered electrophoretic mobility, confocal microscopy and PEG estimation by ELISA. The post-inserted HDAS-PEG desorbed at approximately half the rate at which post-inserted DSPE-PEG desorbed from the liposome surface. HDAS-PEG significantly reduced liposome-induced complement activation (C4d, Bb and SC5b); HDAS-PEG was more effective than more commonly used DSPE-PEG in this capacity. For studying circulation persistence, the liposomes were labeled with 99mTc radionuclide and administered in rats. 99mTc-HDAS-PEG-liposomes showed prolonged persistence in blood as compared to that shown by 99mTc-plain liposomes. After 24 h of administration, < 1% of 99mTc-plain liposomes remained in blood, whereas approximately 28% of injected 99mTc-HDAS-PEG-liposomes were present in blood. In comparison, only 4.8% of 99mTc-DSPE-PEG-liposomes was measured in blood after 24 h. As expected, the clearance route of the liposomes was through liver and spleen. These results demonstrate the potential of a novel non-phosphoryl HDAS-PEG for surface modification of preformed liposomes with a goal of prolonging their circulation persistence and more effective inhibition of complement activation. PMID:23419666

Colonoscopy preparation: polyethylene glycol with Gatorade is as safe and efficacious as four liters of polyethylene glycol with balanced electrolytes.

PubMed

McKenna, Thomas; Macgill, Alice; Porat, Gail; Friedenberg, Frank K

2012-12-01

Four liters of polyethylene glycol 3350 (PEG) with balanced electrolytes for colonoscopy preparation has had poor acceptance. Another approach is the use of electrolyte-free PEG combined with 1.9 L of Gatorade. Despite its widespread use, there are no data on metabolic safety and minimal data on efficacy. Our aim was to assess the efficacy and electrolyte safety of these two PEG-based preparations. This was a prospective, randomized, single-blind, non-inferiority trial. Patients were randomized to 238 g PEG + 1.9 L Gatorade or 4 L of PEG-ELS containing 236 g PEG. Split dosing was not performed. On procedure day blood was drawn for basic chemistries. The primary outcome was preparation quality from procedure photos using the Boston Bowel Preparation Scale. We randomized 136 patients (66 PEG + Gatorade, 70 PEG-ELS). There were no differences in preparation scores between the two agents in the ITT analysis (7.2 ± 1.9 for PEG-ELS and 7.0 ± 2.1 for PEG + Gatorade; p = 0.45). BBPS scores were identical for those who completed the preparation and dietary instructions as directed (7.4 ± 1.7 for PEG-ELS, and 7.4 ± 1.8 for PEG + Gatorade; p = 0.98). There were no statistical differences in serum electrolytes between the two preparations. Patients who received PEG + Gatorade gave higher overall satisfaction scores for the preparation experience (p = 0.001), and had fewer adverse effects. Use of 238 g PEG + 1.9 L Gatorade appears to be safe, better tolerated, and non-inferior to 4 L PEG-ELS. This preparation may be especially useful for patients who previously tolerated PEG-ELS poorly.

Nano-hydrogels of methoxy polyethylene glycol-grafted branched polyethyleneimine via biodegradable cross-linking of Zn2+-ionomer micelle template

NASA Astrophysics Data System (ADS)

Abolmaali, Samira Sadat; Tamaddon, Ali Mohammad; Dinarvand, Rasoul

2013-12-01

Soft polymeric nanomaterials were synthesized by the template-assisted method involving self-association of methoxy polyethylene glycol- g-branched polyethyleneimine (mPEG- g-branched PEI) ionomer by transition metal ions such as Zn2+ followed by chemical cross-linking of the polyamine core by dithiopropionic acid. The formation of donor-acceptor complexes of Zn2+ and PEI ionomer was characterized by FT-IR spectroscopy and potentiometric titration. Turbidimetry was performed to study the solution property of the complexes which depended on pH, relative weight fraction of mPEG, and the molar ratio of Zn2+. The cross-linking reaction was studied by TNBS assay, 1H-NMR, and size exclusion chromatography. Upon removal of Zn2+ from cl-mPEG- g-branched PEI/Zn2+ at pH 3 by dialysis, the resulting cross-linked self-assembly represented a uniform, stable, and less positively charged hydrogel-like nanosphere with an intensity-averaged size ranging from 150 to 250 nm as determined by a Zetasizer. Atomic forced microscopy imaging was performed in intermittent contact mode in air that revealed discrete and oval-to-spherically shaped particles with average sizes ranging from 40 to 50 nm depending on the degree of cross-linking. This functional nanocarrier is expected to exhibit some key features such as active encapsulation of negatively charged hydrophilic agents in the swollen core of polyamine network and a hydrophilic mPEG shell which provides an increased solubility and passive targeting of active pharmaceutical agents to impaired tissues. The nano-hydrogels especially at 12 % degrees of cross-link demonstrated excellent biocompatibility determined by different experiments such as albumin aggregation, erythrocyte aggregation, hemolysis, and MTT cytotoxicity assay. Moreover, biodegradability of the cross-links as shown by the Ellman assay can offer a time-dependent degradation and redox-stimulated release of active agents.

Comparative analysis of EV isolation procedures for miRNAs detection in serum samples.

PubMed

Andreu, Zoraida; Rivas, Eva; Sanguino-Pascual, Aitana; Lamana, Amalia; Marazuela, Mónica; González-Alvaro, Isidoro; Sánchez-Madrid, Francisco; de la Fuente, Hortensia; Yáñez-Mó, María

2016-01-01

Extracellular vesicles (EVs) are emerging as potent non-invasive biomarkers. However, current methodologies are time consuming and difficult to translate to clinical practice. To analyse EV-encapsulated circulating miRNA, we searched for a quick, easy and economic method to enrich frozen human serum samples for EV. We compared the efficiency of several protocols and commercial kits to isolate EVs. Different methods based on precipitation, columns or filter systems were tested and compared with ultracentrifugation, which is the most classical protocol to isolate EVs. EV samples were assessed for purity and quantity by nanoparticle tracking analysis and western blot or cytometry against major EV protein markers. For biomarker validation, levels of a set of miRNAs were determined in EV fractions and compared with their levels in total serum. EVs isolated with precipitation-based methods were enriched for a subgroup of miRNAs that corresponded to miRNAs described to be encapsulated into EVs (miR-126, miR-30c and miR-143), while the detection of miR-21, miR-16-5p and miR-19a was very low compared with total serum. Our results point to precipitation using polyethylene glycol (PEG) as a suitable method for an easy and cheap enrichment of serum EVs for miRNA analyses. The overall performance of PEG was very similar, or better than other commercial precipitating reagents, in both protein and miRNA yield, but in comparison to them PEG is much cheaper. Other methods presented poorer results, mostly when assessing miRNA by qPCR analyses. Using PEG precipitation in a longitudinal study with human samples, we demonstrated that miRNA could be assessed in frozen samples up to 8 years of storage. We report a method based on a cut-off value of mean of fold EV detection versus serum that provides an estimate of the degree of encapsulation of a given miRNA.

Partitioning of human and sheep forms of the pathogenic prion protein during the purification of therapeutic proteins from human plasma.

PubMed

Stenland, Christopher J; Lee, Douglas C; Brown, Paul; Petteway, Stephen R; Rubenstein, Richard

2002-11-01

Therapeutic proteins derived from human plasma and other biologic sources have demonstrated an excellent safety record relative to the potential threat of transmissible spongiform encephalopathy (TSE) transmission. Previously, hamster-adapted scrapie was used as a model agent to assess TSE clearance in purification steps leading to the isolation of biopharmaceutical proteins. The current study investigated the validity of hamster scrapie as a model for human TSE clearance studies. The partitioning of the pathogenic forms of the prion protein associated with human variant CJD (PrP(vCJD)), human sporadic CJD (PrP(sCJD)) and Gerstmann-Sträussler-Scheinker (PrP(GSS)) syndrome was compared to the partitioning of hamster scrapie (PrP(Sc)) in three plasma protein purification steps. Sheep scrapie (PrP(Sc)) was similarly evaluated. The starting materials for three plasma protein purification steps, cryoseparation, 3 percent PEG separation, and 11.5 percent PEG separation, were spiked with brain homogenates containing human PrP(vCJD), human PrP(sCJD), human PrP(GSS), sheep PrP(Sc), and hamster 263K PrP(Sc). The partitioning of the pathogenic form of the PrP was analyzed. Clearance of the pathogenic form of the PrP was measured relative to the effluent fraction. Regardless of the source of the pathogenic prion, clearance was similar to hamster PrP(Sc). A nominal amount of clearance (approx., 1 log), an intermediate amount of clearance (approx., 2 log), and a substantial amount of clearance (> or = 3 log) were observed for the cryoseparation, 3 percent PEG separation, and 11.5 percent PEG separation steps, respectively. In the latter step, no PrP was detected in the effluents. These data demonstrate that human prions, including vCJD prions, can be removed during the purification of human therapeutic proteins and indicate that partitioning of human prions is similar to that observed in the hamster scrapie model.

A prospective audit of the efficacy, safety, and acceptability of low-volume polyethylene glycol (2 L) versus standard volume polyethylene glycol (4 L) versus magnesium citrate plus stimulant laxative as bowel preparation for colonoscopy.

PubMed

Kelly, Nicholas Michael; Rodgers, Colin; Patterson, Neil; Jacob, Sudheer George; Mainie, Inder

2012-08-01

High-quality video colonoscopy requires adequate preparation of the bowel to ensure both adequate procedure completion rates and polyp detection rates. We sought to examine our practice to determine which bowel preparation cleansed most effectively in our patients. A prospective audit of the efficacy, safety, and acceptability of low-volume polyethylene glycol (2-L Moviprep; Norgine Pharmaceuticals) versus standard volume polyethylene glycol (4-L KleanPrep; Norgine Pharmaceuticals) versus magnesium citrate (Citramag; Sanochemia UK Ltd.) plus stimulant laxative as bowel preparation for colonoscopy. District General Hospital. Patients attending for day case colonoscopy. Not applicable. Overall cleansing grades of preparations used: patient compliance, taste, and acceptability. A prospective audit of patient experience of taking bowel preparation and blinded colonic scoring assessment of bowel cleansing of each of the tested regimes. A total of 258 (female,138; 53.5%) patients were recruited, 91 in the KleanPrep group (F:45, 49.5%), 86 patients in the Moviprep group (female, 45; 52.3%), and 81 in the Senna/Citramag group (female, 44; 54.3%). Significantly more patients were unable to take the prescribed dose of KleanPrep when compared with the other 2 regimes (19.6%; P<0.0001 vs. Moviprep; P<0.0001 vs. Senna/Citramag). A total of 45.65% of patients reported KleanPrep as tasting unpleasant. This was significantly more than both Moviprep (10.47%; P=0.008) and Senna/Citramag (9.88%; P<0.0001). The overall cleansing efficacy across the 3 groups (those with grades A or B) was 73.9%, 74.5%, and 86.5% for KleanPrep, Moviprep, and Senna/Citramag, respectively. In this series Senna/Citramag proved significantly better at bowel cleansing than KleanPrep (P<0.05) and it showed a trend toward better cleansing when compared with Moviprep (P=0.08). Nonrandomized trial. Split-dosing regime for morning and afternoon lists may have confounded results. In summary, low-volume PEG (Moviprep) and Senna/Citramag combination were better tolerated than large volume PEG with Senna/Citramag providing superior mucosal cleansing.

Unconfined laminar nanofluid flow and heat transfer around a rotating circular cylinder in the steady regime

NASA Astrophysics Data System (ADS)

Bouakkaz, Rafik; Salhi, Fouzi; Khelili, Yacine; Quazzazi, Mohamed; Talbi, Kamel

2017-06-01

In this work, steady flow-field and heat transfer through a copper- water nanofluid around a rotating circular cylinder with a constant nondimensional rotation rate α varying from 0 to 5 was investigated for Reynolds numbers of 5-40. Furthermore, the range of nanoparticle volume fractions considered is 0-5%. The effect of volume fraction of nanoparticles on the fluid flow and heat transfer characteristics are carried out by using a finite-volume method based commercial computational fluid dynamics solver. The variation of the local and the average Nusselt numbers with Reynolds number, volume fractions, and rotation rate are presented for the range of conditions. The average Nusselt number is found to decrease with increasing value of the rotation rate for the fixed value of the Reynolds number and volume fraction of nanoparticles. In addition, rotation can be used as a drag reduction technique.

Influence of different peg length in glenoid bone loss: A biomechanical analysis regarding primary stability of the glenoid baseplate in reverse shoulder arthroplasty.

PubMed

Königshausen, M; Jettkant, B; Sverdlova, N; Ehlert, C; Gessmann, J; Schildhauer, T A; Seybold, D

2015-01-01

There is no biomechanical basis to determine the influence of different length of the central peg of the baseplate anchored within the native scapula in glenoid defect reconstruction in cases of degenerative or posttraumatic glenoid bone loss in reversed shoulder arthroplasty. The purpose of this study was to analyse the stability of different peg lengths used in glenoid bone loss in reversed shoulder arthroplasty. Different lengths of metaglene pegs with different depths of peg anchorage performed with or without metaglene screws in sawbone foam blocks were loaded in vertical and horizontal directions for differentiating load capacities. Simulated physiological loadings were then applied to the peg implants to determine the limits of loading in each depth of anchorage. The loading capacity of the implant was reduced as less of the peg was anchored. The vertically loaded implants showed a significantly higher stability, in contrast to those loaded horizontally at a corresponding peg length and depth of anchorage (p < 0.05). The tests revealed that the metaglene screws are more essential for primary stability than is the peg particularly in the vertically directed loadings (2/3 anchored: peg contributed to 28% of the stability, 1/3 anchorage: peg contributed to 12%). Under the second test conditions, the lowest depth of peg anchorage (1/3) resulted in 322 Newtons [N] in the long peg with a vertical loading direction, and in 130 N in the long peg with a horizontal loading direction (p < 0.05). The pegs should be anchored as deeply as possible into the native scapula bone stock. The metaglene screws play a major role in the initial stability, in contrast to the peg, and they become more important when the depth of the peg anchorage is reduced. If possible, four metaglene screws should be used in cases of uncontained bone loss to guarantee the highest stability.

Investigation of PEG crystallization in frozen and freeze-dried PEGylated recombinant human growth hormone-sucrose systems: implications on storage stability.

PubMed

Bhatnagar, Bakul S; Martin, Susan W H; Hodge, Tamara S; Das, Tapan K; Joseph, Liji; Teagarden, Dirk L; Shalaev, Evgenyi Y; Suryanarayanan, Raj

2011-08-01

The objectives of the current study were to investigate (i) the phase behavior of a PEGylated recombinant human growth hormone (PEG-rhGH, ∼60 kDa) during freeze-drying and (ii) its storage stability. The phase transitions during freeze-thawing of an aqueous solution containing PEG-rhGH and sucrose were characterized by differential scanning calorimetry. Finally, PEG-rhGH and sucrose formulations containing low, medium, and high polyethylene glycol (PEG) to sucrose ratios were freeze-dried in dual-chamber syringes and stored at 4°C and 25°C. Chemical decomposition (methionine oxidation and deamidation) and irreversible aggregation were characterized by size-exclusion and ion-exchange chromatography, and tryptic mapping. PEG crystallization was facilitated when it was covalently linked with rhGH. When the solutions were frozen, phase separation into PEG-rich and sucrose-rich phases facilitated PEG crystallization and the freeze-dried cake contained crystalline PEG. Annealing caused PEG crystallization and when coupled with higher drying temperatures, the primary drying time decreased by up to 51%. When the freeze-dried cakes were stored at 4°C, while there was no change in the purity of the PEG-rhGH monomer, deamidation was highest in the formulations with the lowest PEG to sucrose ratio. When stored at 25°C, this composition also showed the most pronounced decrease in monomer purity, the highest level of aggregation, and deamidation. Furthermore, an increase in PEG crystallinity during storage was accompanied by a decrease in PEG-rhGH stability. Interestingly, during storage, there was no change in PEG crystallinity in formulations with medium and high PEG to sucrose ratios. Although PEG crystallization during freeze-drying did not cause protein degradation, crystallization during storage might have influenced protein stability. Copyright © 2011 Wiley-Liss, Inc.

The role of facilitated diffusion in oxygen transport by cell-free hemoglobins: implications for the design of hemoglobin-based oxygen carriers.

PubMed

McCarthy, M R; Vandegriff, K D; Winslow, R M

2001-08-30

We compared rates of oxygen transport in an in vitro capillary system using red blood cells (RBCs) and cell-free hemoglobins. The axial PO(2) drop down the capillary was calculated using finite-element analysis. RBCs, unmodified hemoglobin (HbA(0)), cross-linked hemoglobin (alpha alpha-Hb) and hemoglobin conjugated to polyethylene-glycol (PEG-Hb) were evaluated. According to their fractional saturation curves, PEG-Hb showed the least desaturation down the capillary, which most closely matched the RBCs; HbA(0) and alpha alpha-Hb showed much greater desaturation. A lumped diffusion parameter, K*, was calculated based on the Fick diffusion equation with a term for facilitated diffusion. The overall rates of oxygen transfer are consistent with hemoglobin diffusion rates according to the Stokes-Einstein Law and with previously measured blood pressure responses in rats. This study provides a conceptual framework for the design of a 'blood substitute' based on mimicking O(2) transport by RBCs to prevent autoregulatory changes in blood flow and pressure.

Numerical Investigation on Absorption Enhancement of Black Carbon Aerosols Partially Coated With Nonabsorbing Organics

NASA Astrophysics Data System (ADS)

Zhang, Xiaolin; Mao, Mao; Yin, Yan; Wang, Bin

2018-01-01

This study numerically evaluates the effects of aerosol microphysics, including coated volume fraction of black carbon (BC), shell/core ratio, and size distribution, on the absorption enhancement (Eab) of polydisperse BC aggregates partially coated by organics, which is calculated by the exact multiple-sphere T-matrix method. The coated volume fraction of BC plays a substantial role in determining the absorption enhancement of partially coated BC aggregates, which typically have an Eab in the range of 1.0-2.0 with a larger value for larger coated volume fraction of BC as the shell/core ratio, BC geometry, and size distribution are fixed. The shell/core ratio, BC geometry, and size distribution have little impact on the Eab of coated BC with small coated volume fraction of BC, while they become significant for large coated volume fraction of BC. The Eab of partially coated BC particles can be slightly less than 1.0 for the large BC in the accumulation mode exhibiting large shell/core ratio and small coated volume fraction of BC, indicating that the absorption shows even slight decrease relative to uncoated BC particles. For partially coated BC aggregates in the accumulation and coarse modes, the refractive index uncertainties of BC result in the Eab differences of less than 9% and 2%, respectively, while those of organics can induce larger variations with the maximum differences up to 22% and 18%, respectively. Our study indicates that accounting for particle coating microphysics, particularly the coated volume fraction of BC, can potentially help to understand the differences in observations of largely variable absorption enhancements over various regions.

Artesunate-modified nano-graphene oxide for chemo-photothermal cancer therapy

PubMed Central

Pang, Yilin; Mai, Zihao; Wang, Bin; Wang, Lu; Wu, Liping; Wang, Xiaoping; Chen, Tongsheng

2017-01-01

Poor water-solubility of artesunate (ARS) hampers its clinical application. We here covalently linked ARS to PEGylated nanographene oxide (nGO-PEG) to obtain ARS-modified nGO-PEG (nGO-PEG-ARS) with excellent photothermal effect and dispersibility in physiological environment. nGO-PEG-ARS induced reactive oxygen species (ROS) and peroxynitrite (ONOO─) generations. Although nGO-PEG with near-infrared (NIR) irradiation did not induce cytotoxicity, the photothermal effect of nGO-PEG under NIR irradiation enhanced not only cell uptake but also ONOO─ generation of nGO-PEG-ARS, resulting in the synergistic chemo-photothermal effect of nGO-PEG-ARS in killing HepG2 cells. Pretreatment with Fe(III) 5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinato chloride (FeTTPS, a ONOO─ scavenger) instead of antioxidant N-Acetyle-Cysteine (NAC, an ROS scavenger) significantly blocked the cytotoxicity of nGO-PEG-ARS with or without NIR irradiation, demonstrating that ONOO─ instead of ROS dominated the synergistic chemo-photothermal anti-cancer action of nGO-PEG-ARS. nGO-PEG-ARS with NIR irradiation resulted in a complete tumor cure within 15 days earlier than other treatment groups, and did not induce apparent histological lesion for the mice treated with nGO-PEG-ARS with or without NIR irradiation for 30 days, further proving the synergistic chemo-photothermal anti-cancer effect of nGO-PEG-ARS. Collectively, nGO-PEG-ARS is a versatile nano-platform for multi-modal synergistic cancer therapy. PMID:29212190

Hyaluronic Acid Hydrogel Functionalized with Self-Assembled Micelles of Amphiphilic PEGylated Kartogenin for the Treatment of Osteoarthritis.

PubMed

Kang, Mi-Lan; Jeong, Se-Young; Im, Gun-Il

2017-07-01

Synthetic hyaluronic acid (HA) containing a covalently integrated drug is capable of releasing therapeutic molecules and is an attractive candidate for the intra-articular treatment of osteoarthritis (OA). Herein, self-assembled PEGylated kartogenin (PEG/KGN) micelles consisting of hydrophilic polyethylene glycol (PEG) and hydrophobic KGN, which has been shown to induce chondrogenesis in human mesenchymal stem cells, were prepared by covalent crosslinking. HA hydrogels containing PEG/KGN micelles (HA/PEG/KGN) were prepared by covalently bonding PEG chains to HA. The physicochemical properties of the HA/PEG/KGN conjugate gels were investigated using Fourier transform infrared spectroscopy, 1 H NMR, dynamic light scattering (DLS), and scanning electron microscopy (SEM). HA/PEG/KGN gels exhibited larger micelles in aqueous solution than PEG/KGN. SEM images of PEG/KGN micelles showed a dark core and a bright shell, whereas PEG/KGN micelles covalently integrated into HA had an irregular oval shape. Covalent integration of PEG/KGN micelles in HA hydrogels significantly reduced drug release rates and provided sustained release over a prolonged period of time. HA/PEG/KGN hydrogels were degradable enzymatically by collagenase and hyaluronidase in vitro. Injection of HA/PEG/KGN hydrogels into articular cartilage significantly suppressed the progression of OA in rats compared with free-HA hydrogel injection. These results suggest that the HA/PEG/KGN hydrogels have greater potency than free-HA hydrogels against OA as biodegradable synthetic therapeutics.

A study on the effects of temperature and volume fraction on thermal conductivity of copper oxide nanofluid.

PubMed

Jwo, Ching-Song; Chang, Ho; Teng, Tun-Ping; Kao, Mu-Jnug; Guo, Yu-Ting

2007-06-01

By using copper oxide nanofluid fabricated by the self-made Submerged Arc Nanofluid Synthesis System (SANSS), this paper measures the thermal conductivity under different volume fractions and different temperatures by thermal properties analyzer, and analyzes the correlation among the thermal conductivity, volume fraction, and temperature of nanofluid. The CuO nanoparticles used in the experiment are needle-like, with a mean particle size of about 30 nm. They can be stably suspended in deionized water for a long time. The experimental results show that under the condition that the temperature is 40 degrees C, when the volume fraction of nanofluid increases from 0.2% to 0.8%, the thermal conductivity increment of the prepared nanofluid towards deionized water can be increased from 14.7% to 38.2%. Under the condition that the volume fraction is 0.8%, as the temperature of nanofluid rises from 5 degrees C to 40 degrees C, the thermal conductivity increment of the prepared nanofluid towards deionized water increases from 5.9% to 38.2%. Besides, the effects of temperature change are greater than the effects of volume fraction on the thermal conductivity of nanofluid. Therefore, when the self-made copper oxide nanofluid is applied to the heat exchange device under medium and high temperature, an optimal radiation effect can be acquired.

Simultaneous integrated vs. sequential boost in VMAT radiotherapy of high-grade gliomas.

PubMed

Farzin, Mostafa; Molls, Michael; Astner, Sabrina; Rondak, Ina-Christine; Oechsner, Markus

2015-12-01

In 20 patients with high-grade gliomas, we compared two methods of planning for volumetric-modulated arc therapy (VMAT): simultaneous integrated boost (SIB) vs. sequential boost (SEB). The investigation focused on the analysis of dose distributions in the target volumes and the organs at risk (OARs). After contouring the target volumes [planning target volumes (PTVs) and boost volumes (BVs)] and OARs, SIB planning and SEB planning were performed. The SEB method consisted of two plans: in the first plan the PTV received 50 Gy in 25 fractions with a 2-Gy dose per fraction. In the second plan the BV received 10 Gy in 5 fractions with a dose per fraction of 2 Gy. The doses of both plans were summed up to show the total doses delivered. In the SIB method the PTV received 54 Gy in 30 fractions with a dose per fraction of 1.8 Gy, while the BV received 60 Gy in the same fraction number but with a dose per fraction of 2 Gy. All of the OARs showed higher doses (Dmax and Dmean) in the SEB method when compared with the SIB technique. The differences between the two methods were statistically significant in almost all of the OARs. Analysing the total doses of the target volumes we found dose distributions with similar homogeneities and comparable total doses. Our analysis shows that the SIB method offers advantages over the SEB method in terms of sparing OARs.

Final report on the safety assessment of Triethylene Glycol and PEG-4.

PubMed

2006-01-01

Triethylene Glycol and PEG-4 (polyethylene glycol) are polymers of ethylene oxide alcohol. Triethylene Glycol is a specific three-unit chain, whereas PEG-4 is a polymer with an average of four units, but may contain polymers ranging from two to eight ethylene oxide units. In the same manner, other PEG compounds, e.g., PEG-6, are mixtures and likely contain some Triethylene Glycol and PEG-4. Triethylene Glycol is a fragrance ingredient and viscosity decreasing agent in cosmetic formulations, with a maximum concentration of use of 0.08% in skin-cleansing products. Following oral doses, Triethylene Glycol and its metabolites are excreted primarily in urine, with small amounts released in feces and expired air. With oral LD50 values in rodents from 15 to 22 g/kg, this compound has little acute toxicity. Rats given short term oral doses of 3% in water showed no signs of toxicity, whereas all rats given 10% died by the 12th day of exposure. At levels up to 1 g/m3, rats exposed to aerosolized Triethylene Glycol for 6 h per day for 9 days showed no signs of toxicity. Rats fed a diet containing 4% Triethylene Glycol for 2 years showed no signs of toxicity. There were no treatment-related effects on rats exposed to supersaturated Triethylene Glycol vapor for 13 months nor in rats that consumed 0.533 cc Triethylene Glycol per day in drinking water for 13 months. Triethylene Glycol was not irritating to the skin of rabbits and produced only minimal injury to the eye. In reproductive and developmental toxicity studies in rats and mice, Triethylene Glycol did not produce biologically significant embryotoxicity or teratogenicity. However, some maternal toxicity was seen in dams given 10 ml/kg/day during gestation. Triethylene Glycol was not mutagenic or genotoxic in Ames-type assays, the Chinese hamster ovary mutation assay, and the sister chromatid exchange assays. PEG-4 is a humectant and solvent in cosmetic products, with a maximum concentration of use of 20% in the "other manicuring preparations" product category. This ingredient, with an oral LD50 in rats of 32.77 g/kg, has low acute toxicity. Rats given up to 50,000 ppm PEG-4 in drinking water for 5 days showed no permanent signs of toxicity. Rats given daily oral doses up to 2 g/kg/day of PEG-4 for 33 days showed no signs of toxicity. Undiluted PEG-4 produced only minimal injury to the rabbit eye. PEG-4 was not mutagenic in Ames-type assays, did not induce chromosome aberration in an in vivo bone marrow assay, and was negative for genotoxicity in a dominant lethal assay using rats. Other PEG compounds, which have previously been reviewed by the Cosmetic Ingredient Review (CIR) Expert Panel, e.g., PEG-6, are mixtures that likely include Triethylene Glycol and PEG-4, so these data were also considered. PEG-6 and PEG-8 were not dermal irritants in several rabbit studies. PEG-2 Stearate had a potential for slight irritation in rabbits but was not a sensitizer in guinea pigs. PEG-2 Cocamine was a moderate irritant in rabbits, producing severe erythema. In one dermal study, PEG-2 Cocamine was determined to be corrosive to rabbit skin, causing eschar and necrosis. PEG-6 and PEG-8 caused little to no ocular irritation. PEG-8 was not mutagenic or genotoxic in a Chinese hamster ovary assay, a sister-chromatid exchange assay, and in an unscheduled DNA synthesis assay. In clinical studies on normal skin, PEG-6 and PEG-8 caused mild cases of immediate hypersensitivity; PEG-8 was not a sensitizer; PEG-2 Stearate was not an irritant, a sensitizer, or a photosensitizer; and PEG-6 Stearate was not an irritant or sensitizer. In damaged skin, cases of systemic toxicity and contact dermatitis in burn patients were attributed to a PEG-based topical ointment. The CIR Expert Panel acknowledged the lack of dermal sensitization data for Triethylene Glycol and dermal irritation and sensitization data for PEG-4. That PEG-6, PEG-8, and PEG-2 Stearate were not irritants or sensitizers suggested that Triethylene Glycol and PEG-4 also would not be irritants or sensitizers, and the absence of any reported reactions in the case literature and the professional experience of the Expert Panel further supported the absence of any significant sensitization potential. The need for additional data to demonstrate the safety of PEGs Cocamine was related to the Cocamine moiety and is not relevant here. The Panel reminded formulators of cosmetic products that, as with other PEG compounds, Triethylene Glycol and PEG-4 should not be used on damaged skin because of cases of systemic toxicity and contact dermatitis in burn patients have been attributed to a PEG-based topical ointment. Based on its consideration of the available information, the CIR Expert Panel concluded that Triethylene Glycol and PEG-4 are safe as cosmetic ingredients in the present practices and concentrations of use as described in this safety assessment.

Interfacial effect on physical properties of composite media: Interfacial volume fraction with non-spherical hard-core-soft-shell-structured particles.

PubMed

Xu, Wenxiang; Duan, Qinglin; Ma, Huaifa; Chen, Wen; Chen, Huisu

2015-11-02

Interfaces are known to be crucial in a variety of fields and the interfacial volume fraction dramatically affects physical properties of composite media. However, it is an open problem with great significance how to determine the interfacial property in composite media with inclusions of complex geometry. By the stereological theory and the nearest-surface distribution functions, we first propose a theoretical framework to symmetrically present the interfacial volume fraction. In order to verify the interesting generalization, we simulate three-phase composite media by employing hard-core-soft-shell structures composed of hard mono-/polydisperse non-spherical particles, soft interfaces, and matrix. We numerically derive the interfacial volume fraction by a Monte Carlo integration scheme. With the theoretical and numerical results, we find that the interfacial volume fraction is strongly dependent on the so-called geometric size factor and sphericity characterizing the geometric shape in spite of anisotropic particle types. As a significant interfacial property, the present theoretical contribution can be further drawn into predicting the effective transport properties of composite materials.

Interfacial effect on physical properties of composite media: Interfacial volume fraction with non-spherical hard-core-soft-shell-structured particles

PubMed Central

Xu, Wenxiang; Duan, Qinglin; Ma, Huaifa; Chen, Wen; Chen, Huisu

2015-01-01

Interfaces are known to be crucial in a variety of fields and the interfacial volume fraction dramatically affects physical properties of composite media. However, it is an open problem with great significance how to determine the interfacial property in composite media with inclusions of complex geometry. By the stereological theory and the nearest-surface distribution functions, we first propose a theoretical framework to symmetrically present the interfacial volume fraction. In order to verify the interesting generalization, we simulate three-phase composite media by employing hard-core-soft-shell structures composed of hard mono-/polydisperse non-spherical particles, soft interfaces, and matrix. We numerically derive the interfacial volume fraction by a Monte Carlo integration scheme. With the theoretical and numerical results, we find that the interfacial volume fraction is strongly dependent on the so-called geometric size factor and sphericity characterizing the geometric shape in spite of anisotropic particle types. As a significant interfacial property, the present theoretical contribution can be further drawn into predicting the effective transport properties of composite materials. PMID:26522701

Improved Micellar Formulation for Enhanced Delivery for Paclitaxel.

PubMed

Xu, Jieni; Zhang, Xiaolan; Chen, Yichao; Huang, Yixian; Wang, Pengcheng; Wei, Yuan; Ma, Xiaochao; Li, Song

2017-01-03

We have previously improved the bioactivity of PEG 5k -FTS 2 system by incorporating disulfide bond (PEG 5k -S-S-FTS 2 ) to facilitate the release of farnesyl thiosalicylic acid (FTS).1 Later, fluorenylmethyloxycarbonyl (Fmoc) moiety has been introduced to PEG 5k -FTS 2 system (PEG 5k -Fmoc-FTS 2 ) in order to enhance drug loading capacity (DLC) and formulation stability.2 In this study, we have brought in both disulfide linkage and Fmoc group to PEG 5k -FTS 2 to form a simple PEG 5k -Fmoc-S-S-FTS 2 micellar system. PEG 5k -Fmoc-S-S-FTS 2 conjugate formed filamentous micelles with a ∼10-fold decrease in critical micellar concentration (CMC). Compared with PEG 5k -Fmoc-FTS 2 , our novel system exhibited further strengthened DLC and colloidal stability. More FTS was freed from PEG 5k -Fmoc-S-S-FTS 2 in treated tumor cells compared to PEG 5k -Fmoc-FTS 2 , which was correlated to an increased cytotoxicity of our new carrier in these cancer cells. After loading Paclitaxel (PTX) into PEG 5k -Fmoc-S-S-FTS 2 micelles, it showed more potent efficiency in inhibition of tumor cell proliferation than Taxol and PTX-loaded PEG 5k -Fmoc-FTS 2 . PTX release kinetics of PTX/PEG 5k -Fmoc-S-S-FTS 2 was much slower than that of Taxol and PTX/PEG 5k -Fmoc-FTS 2 in normal release medium. In contrast, in glutathione (GSH)-containing medium, PTX in PEG 5k -Fmoc-S-S-FTS 2 micelles revealed faster and more complete release. Pharmacokinetics and tissue distribution study showed that our PEG 5k -Fmoc-S-S-FTS 2 system maintained PTX in circulation for a longer time and delivered more PTX to tumor sites with less accumulation in major organs. Finally, PTX-loaded PEG 5k -Fmoc-S-S-FTS 2 micelles resulted in a superior therapeutic effect in vivo compared to Taxol and PTX formulated in PEG 5k -Fmoc-FTS 2 micelles.

Bisacodyl plus split 2-L polyethylene glycol-citrate-simethicone improves quality of bowel preparation before screening colonoscopy

PubMed Central

Valiante, Flavio; Bellumat, Angelo; De Bona, Manuela; De Boni, Michele

2013-01-01

AIM: To compare the bowel cleansing efficacy, tolerability and acceptability of split 2-L polyethylene glycol (PEG)-citrate-simethicone (PEG-CS) plus bisacodyl (BIS) vs 4-L PEG for fecal occult blood test-positive screening colonoscopy. METHODS: This was a randomised, observer-blind comparative study. Two hundred and sixty-four subjects underwent screening colonoscopy (mean age 62.5 ± 7.4 years, male 61.7%). The primary objective of the study was to compare the bowel cleansing efficacy of the two preparations. Interventions: BIS plus PEG-CS: 3 tablets of 5-mg BIS at 16:00, PEG-CS 1-L at 19:00 and 1-L at 7:00, 4-L PEG: 3-L at 17:00, and 1-L at 7:00. Colonoscopy was carried out after 11:00, at least 3 h after the completion of bowel preparation. Bowel cleansing was evaluated using the Harefield Cleansing Scale. RESULTS: Bowel preparation was successful for 92.8% of subjects in the PEG-CS group and for 92.1% of subjects in the 4-L PEG (RR = 1.01; 95%CI: 0.94-1.08). BIS + PEG-CS was better tolerated than 4-L PEG. A greater rate of patients in the BIS + PEG-CS group had no difficulty and/or were willing to repeat the same preparation compared to split-dose 4-L PEG group. Subjects in the BIS + PEG-CS group rated the prep as good or satisfactory in 90.6% as compared to 77% in the 4-L PEG (P = 0.003). Subjects receiving BIS + PEG-CS stated they fully adhered to instructions drinking all the 2-L solution in 97.1% compared with 87.3% in the 4-L PEG (P = 0.003). CONCLUSION: BIS plus split 2-L PEG-CS was as effective as but better tolerated and accepted than split 4-L PEG for screening colonoscopy. This new procedure may increase the positive attitude and participation to colorectal cancer screening colonoscopy. PMID:24023492

Changes in chemical components and cytotoxicity at different maturity stages of Pleurotus eryngii fruiting body.

PubMed

Cui, Fengjie; Li, Yunhong; Yang, Yan; Sun, Wenjing; Wu, Di; Ping, Lifeng

2014-12-31

The present study investigated the changes of the chemical components and cytotoxicity potency at 5 developmental stages of Pleurotus eryngii fruiting body. The carbohydrate and protein contents increased along the maturity of fruiting body while fat content decreased. By comparison, the polysaccharide-protein fractions had the highest antiproliferative effect on SGC-7901 and HepG-2 cells in vitro and increasing activity with growing maturity of P. eryngii fruiting body.The maturation process increased the protein content and acid property through the enhanced relative abundance of Asp, Thr, and Glu in polysaccharide-protein fractions. Further purification and electrophoresis identified that the polysaccharide-protein PEG-1with three subunits possibly was the target cytotoxical component. Our findings proved that mature fruiting body of P. eryngii containing these polysaccharide-proteins possessed highly nutritional values and therapeutical benefits.

Unexpected electronic perturbation effects of simple PEG environments on the optical properties of small cadmium chalcogenide clusters

NASA Astrophysics Data System (ADS)

Fukunaga, Naoto; Konishi, Katsuaki

2015-12-01

Poly(ethylene glycol) (PEG) has been widely used for the surface protection of inorganic nanoobjects because of its virtually `inert' nature, but little attention has been paid to its inherent electronic impacts on inorganic cores. Herein, we definitively show, through studies on optical properties of a series of PEG-modified Cd10Se4(SR)10 clusters, that the surrounding PEG environments can electronically affect the properties of the inorganic core. For the clusters with PEG units directly attached to an inorganic core (R = (CH2CH2O)nOCH3, 1-PEGn, n = 3, ~7, ~17, ~46), the absorption bands, associated with the low-energy transitions, continuously blue-shifted with the increasing PEG chain length. The chain length dependencies were also observed in the photoluminescence properties, particularly in the excitation spectral profiles. By combining the spectral features of several PEG17-modified clusters (2-Cm-PEG17 and 3) whose PEG and core units are separated by various alkyl chain-based spacers, it was demonstrated that sufficiently long PEG units, including PEG17 and PEG46, cause electronic perturbations in the cluster properties when they are arranged near the inorganic core. These unique effects of the long-PEG environments could be correlated with their large dipole moments, suggesting that the polarity of the proximal chemical environment is critical when affecting the electronic properties of the inorganic cluster core.Poly(ethylene glycol) (PEG) has been widely used for the surface protection of inorganic nanoobjects because of its virtually `inert' nature, but little attention has been paid to its inherent electronic impacts on inorganic cores. Herein, we definitively show, through studies on optical properties of a series of PEG-modified Cd10Se4(SR)10 clusters, that the surrounding PEG environments can electronically affect the properties of the inorganic core. For the clusters with PEG units directly attached to an inorganic core (R = (CH2CH2O)nOCH3, 1-PEGn, n = 3, ~7, ~17, ~46), the absorption bands, associated with the low-energy transitions, continuously blue-shifted with the increasing PEG chain length. The chain length dependencies were also observed in the photoluminescence properties, particularly in the excitation spectral profiles. By combining the spectral features of several PEG17-modified clusters (2-Cm-PEG17 and 3) whose PEG and core units are separated by various alkyl chain-based spacers, it was demonstrated that sufficiently long PEG units, including PEG17 and PEG46, cause electronic perturbations in the cluster properties when they are arranged near the inorganic core. These unique effects of the long-PEG environments could be correlated with their large dipole moments, suggesting that the polarity of the proximal chemical environment is critical when affecting the electronic properties of the inorganic cluster core. Electronic supplementary information (ESI) available: Details of synthetic procedures and characterisation data of the PEGylated thiols and clusters and additional absorption, photoluminescence emission and excitation spectral data. See DOI: 10.1039/c5nr06307h

Sensitive and rapid detection of anti-PEG in blood using surface plasmon resonance sensor (Conference Presentation)

NASA Astrophysics Data System (ADS)

Sun, Fang; Jiang, Shaoyi; Yu, Qiuming

2016-03-01

Polyethylene glycol (PEG) is widely used to modify many therapeutic proteins and nanoparticles to reduce their immunogenicity and to improve their pharmacokinetic and therapeutic properties. It is generally accepted that PEG is non-immunogenic and non-antigenic. However, an emerging of literature and studies shows that the immune system can generate specific antibodies binding PEG. These anti-PEG antibodies not only correlate with adverse reactions appeared after patient infusions, but are also found to be the reason for therapeutic efficacy loss during chronical administrations. In addition, because of constant exposure to PEG in daily consumer products including detergents, processed food and cosmetics, a substantial proportion of the population has likely developed anti-PEG immunity. Thus a method to quickly and accurately measure the anti-PEG antibody level is desired. Nevertheless, the gold standard to detect anti-PEG antibodies is ELISA, which is costly and time-consuming especially for quantification. Herein, we demonstrated the anti-PEG measurement in blood serum using surface plasmon resonance (SPR) sensor. Several PEG-based surface functionalization on SPR sensor chip were studied in terms of protein resistance and the limit of detection (LOD) of anti-PEG. The quantitative detection can be achieved in less than 30 min with LOD comparable to ELISA. Furthermore, the IgG and IgM of anti-PEG can be differentiated by following the secondary antibody.

Synthesis, characterization, and biocompatibility of alternating block polyurethanes based on PLA and PEG.

PubMed

Mei, Tingzhen; Zhu, Yonghe; Ma, Tongcui; He, Tao; Li, Linjing; Wei, Chiju; Xu, Kaitian

2014-09-01

A series of alternating block polyurethanes (abbreviated as PULA-alt-PEG) and random block polyurethanes (abbreviated as PULA-ran-PEG) based on poly(L-lactic acid) (PLA) and poly(ethylene glycol) (PEG) were synthesized. The differences of PULA-alt/ran-PEG chemical structure, molecular weight, distribution, thermal properties, mechanical properties and static contact angle were systematically investigated. The PULA-alt/ran-PEG polyurethanes exhibited low T(g) (-47.3 ∼ -34.4°C), wide mechanical properties (stress σ(t): 4.6-32.6 MPa, modulus E: 11.4-323.9 MPa and strain ε: 468-1530%) and low water contact angle (35.4-51.4°). Scanning electron microscope (SEM) observation showed that PULA-alt-PEG film displays rougher and more patterned surface morphology than PULA-ran-PEG does, due to more regular structures of PULA-alt-PEG. Hydrolytic degradation shows that degradation rate of random block polyurethane series PULA-ran-PEG is higher than the alternating counterpart PULA-alt-PEG. PLA segment degradation is faster than urethane linkage and PEG segment almost does not degrade in the buffer solution. Platelet adhesion study showed that all the polyurethanes possess excellent hemocompatibility. The cell culture assay revealed that PULA-alt/ran-PEG polyurethanes were cell inert and unfavorable for the attachment of rat glial cell due to the hydrophilic characters of the materials. © 2013 Wiley Periodicals, Inc.

The effect of polyoxyethylene polymers on the transport of ranitidine in Caco-2 cell monolayers.

PubMed

Ashiru-Oredope, Diane A I; Patel, Nilesh; Forbes, Ben; Patel, Rajesh; Basit, Abdul W

2011-05-16

Previous in vivo studies using PEG 400 showed an enhancement in the bioavailability of ranitidine. This study investigated the effect of PEG 200, 300 and 400 on ranitidine transport across Caco-2 cells. The effect of PEG polymers (20%, v/v) on the bi-directional flux of (3)H-ranitidine across Caco-2 cell monolayers was measured. The concentration dependence of PEG 400 effects on ranitidine transport was also studied. A specific screen for P-glycoprotein (P-gp) activity was used to test for an interaction between PEG and P-gp. In the absence of PEG, ranitidine transport showed over 5-fold greater flux across Caco-2 monolayers in the secretory than the absorptive direction; efflux ratio 5.38. PEG 300 and 400 significantly reduced this efflux ratio (p<0.05), whereas PEG 200 had no effect (p>0.05). In concordance, PEG 300 and 400 showed an interaction with the P-gp transporter, whereas PEG 200 did not. Interestingly, with PEG 400 a non-linear concentration dependence was seen for the inhibition of the efflux ratio of ranitidine, with a maxima at 1%, v/v (p<0.05). The inhibition of ranitidine efflux by PEG 300 and 400 which interact with P-gp provides a mechanism that may account for the observations of ranitidine absorption enhancement by PEG 400 in vivo. Copyright © 2011 Elsevier B.V. All rights reserved.

Enhanced circulation half-life of site-specific PEGylated rhG-CSF: optimization of PEG molecular weight.

PubMed

Zhai, Yanqin; Zhao, Yongjiang; Lei, Jiandu; Su, Zhiguo; Ma, Guanghui

2009-07-15

Recombinant human granulocyte colony stimulating factor (rhG-CSF) and its PEGylated product "mono-PEG20-GCSF" have already been widely used for treatment of all kinds of neutropenia. However, the high required dosage of mono-PEG20-GCSF made it relatively expensive in clinical use. We postulated that an N-terminal site-specific PEGylated rhG-CSF with higher PEG Mw (PEG30 kDa) might be able to achieve longer circulation half-life while retaining its bioactivity, allowing the reduction of dosage for clinical use. rhG-CSF was PEGylated at the N-terminus by 5 kDa, 10 kDa, 20 kDa and 30 kDa methoxy-poly(ethylene glycol)-propionaldehyde (mPEG-ALD), and the four PEGylates were compared with respect to reaction, separation, characterization and also in vivo/in vitro activity, results showed that the mPEG-ALD of higher Mw demonstrated better N-terminal site-specific selectivity, separation purity and yield. The production cost and in vitro activity of mono-PEG30-GCSF and mono-PEG20-GCSF were almost the same, while mono-PEG30-GCSF showed longer in vivo circulation half-life and 60% higher drug bioavailability than mono-PEG20-GCSF. Consequently, mono-PEG30-GCSF shall be administered at a lower dosage than mono-PEG20-GCSF while retaining the same therapeutic efficacy.

Differences in taste between two polyethylene glycol preparations.

PubMed

Szojda, Maria M; Mulder, Chris J J; Felt-Bersma, Richelle J F

2007-12-01

Polyethylene glycol preparations (PEG) are increasingly used for chronic constipation in both adults and children. There are some suggestions that PEG 4000 with orange flavour (Forlax) tastes better than PEG 3350 which contains salt (Movicolon). Poor taste is an important factor for non-compliance and is one of the leading causes of therapy failure. The aim of the study was to compare the taste of two commonly used PEG preparations, PEG 4000 and PEG 3350. A double-blind, cross over randomised trial. A hundred people were recruited by advertisement. All tasted both preparations without swallowing and after tasting each of the preparations, they rinsed their mouths. Then a score, on a 5-point scale, was given for both preparations. 100 volunteers were included (27 males and 73 females, mean age 36). The taste score for PEG 4000 (mean 3.9, SD 0.7) was significantly better than for PEG 3350 (mean 2.7, SD 0.7) (p<0.0001, Wilcoxon matched pairs test). No difference in gender or age was observed. The volunteers which tasted PEG 3350 liked it more, when they tasted it first rather than when they tasted it after PEG 4000 (p<0.0001). The order in which volunteers tested PEG 4000 had no influence on the taste results. PEG 4000 tastes better than PEG 3350. This may have implications for patient compliance and effectiveness of treatment in patients with chronic constipation.

Predictive Factors for Prophylactic Percutaneous Endoscopic Gastrostomy (PEG) Tube Placement and Use in Head and Neck Patients Following Intensity-Modulated Radiation Therapy (IMRT) Treatment: Concordance, Discrepancies, and the Role of Gabapentin.

PubMed

Yang, Wuyang; McNutt, Todd R; Dudley, Sara A; Kumar, Rachit; Starmer, Heather M; Gourin, Christine G; Moore, Joseph A; Evans, Kimberly; Allen, Mysha; Agrawal, Nishant; Richmon, Jeremy D; Chung, Christine H; Quon, Harry

2016-04-01

The prophylactic placement of a percutaneous endoscopic gastrostomy (PEG) tube in the head and neck cancer (HNC) patient is controversial. We sought to identify factors associated with prophylactic PEG placement and actual PEG use. Since 2010, data regarding PEG placement and use were prospectively recorded in a departmental database from January 2010 to December 2012. HNC patients treated with intensity-modulated radiation therapy (IMRT) were retrospectively evaluated from 2010 to 2012. Variables potentially associated with patient post-radiation dysphagia from previous literature, and our experience was evaluated. We performed multivariate logistic regression on these variables with PEG placement and PEG use, respectively, to compare the difference of association between the two arms. We identified 192 HNC patients treated with IMRT. Prophylactic PEG placement occurred in 121 (63.0 %) patients, with PEG use in 97 (80.2 %) patients. PEG placement was associated with male gender (p < .01), N stage ≥ N2 (p < .05), pretreatment swallowing difficulties (p < .01), concurrent chemotherapy (p < .01), pretreatment KPS ≥80 (p = .01), and previous surgery (p = .02). Concurrent chemotherapy (p = .03) was positively associated with the use of PEG feeding by the patient, whereas pretreatment KPS ≥80 (p = .03) and prophylactic gabapentin use (p < .01) were negatively associated with PEG use. The analysis suggests there were discrepancies between prophylactic PEG tube placement and actual use. Favorable pretreatment KPS, no pretreatment dysphagia, no concurrent chemotherapy, and the use of gabapentin were significantly associated with reduced PEG use. This analysis may help refine the indications for prophylactic PEG placement.

Colonoscopy Preparation: Polyethylene Glycol with Gatorade is as Safe and Efficacious as 4 Liters of Polyethylene Glycol with Balanced Electrolytes

PubMed Central

McKenna, Thomas; Macgill, Alice; Porat, Gail; Friedenberg, Frank K.

2013-01-01

Background Four liters of polyethylene glycol 3350 with balanced electrolytes for colonoscopy preparation has had poor acceptance. Another approach is the use of electrolyte-free PEG combined with 1.9L of Gatorade. Despite its widespread use, there are no data on metabolic safety and minimal data on efficacy. Our aim was to assess the efficacy and electrolyte safety of these two PEG-based preparations. Methods This was a prospective, randomized, single-blind, non-inferiority trial. Patients were randomized to 238g PEG + 1.9L Gatorade or 4L of PEG-ELS containing 236g PEG. Split dosing was not performed. On procedure day blood was drawn for basic chemistries. The primary outcome was preparation quality from procedure photos using the Boston Bowel Preparation Scale. Results We randomized 136 patients (66 PEG + Gatorade, 70 PEG-ELS). There were no differences in preparation scores between the two agents in the ITT analysis (7.2 ± 1.9 for PEG-ELS and 7.0 ± 2.1 for PEG + Gatorade; p = 0.45). BBPS scores were identical for those who completed the preparation and dietary instructions as directed (7.4 ± 1.7 for PEG-ELS, and 7.4 ± 1.8 for PEG + Gatorade; p = 0.98). There were no statistical differences in serum electrolytes between the two preparations. Patients who received PEG + Gatorade gave higher overall satisfaction scores for the preparation experience (p = 0.001), and had fewer adverse effects. Conclusions Use of 238g PEG + 1.9L Gatorade appears to be safe, better tolerated, and non-inferior to 4L PEG-ELS. This preparation may be especially useful for patients who previously tolerated PEG-ELS poorly. PMID:22711499

Local structure of percolating gels at very low volume fractions

NASA Astrophysics Data System (ADS)

Griffiths, Samuel; Turci, Francesco; Royall, C. Patrick

2017-01-01

The formation of colloidal gels is strongly dependent on the volume fraction of the system and the strength of the interactions between the colloids. Here we explore very dilute solutions by the means of numerical simulations and show that, in the absence of hydrodynamic interactions and for sufficiently strong interactions, percolating colloidal gels can be realised at very low values of the volume fraction. Characterising the structure of the network of the arrested material we find that, when reducing the volume fraction, the gels are dominated by low-energy local structures, analogous to the isolated clusters of the interaction potential. Changing the strength of the interaction allows us to tune the compactness of the gel as characterised by the fractal dimension, with low interaction strength favouring more chain-like structures.

Dependence of particle volume fraction on sound velocity and attenuation of EPDM composites.

PubMed

Kim, K S; Lee, K I; Kim, H Y; Yoon, S W; Hong, S H

2007-05-01

The sound velocity and the attenuation coefficient of EPDM (Ethylene-propylene Diene Monomer) composites incorporated with Silicon Carbide particles (SiCp's) of various volume fractions (0-40%) were experimentally and theoretically investigated. For the experiment a through-transmission technique was used. For the theoretical prediction, some mechanical property models such as Reuss model and Coherent Potential Approximation (CPA) model etc. were employed. The experimental results showed that the sound velocity decreased with the increase of the SiCp volume fraction up to 30% and then increased with the 40 vol% specimen. The attenuation coefficient was increased with the increasing SiCp volume fractions. The modified Reuss model with a longitudinal elastic modulus predicted most well the experimental sound velocity and elastic modulus results.

Directed aggregation of carbon nanotube on curved surfaces by polymer induced depletion attraction

NASA Astrophysics Data System (ADS)

Lee, Hsin-Chieh; Jiang, Hong-Ren

2017-12-01

In this study, we show that by chemically grafting macromolecule, polyethylene glycol (PEG), onto CNTs, PEG-CNTs become dispersible in an aqueous solution with tunable depletion interactions with each other. The aggregation of the PEG-CNTs can be controlled by adding PEG polymers into the solution. PEG-CNTs not only aggregate with each other but also tend to aggregate on curved surfaces. Due to this property, we show that PEG-CNTs can be directed to aggregate on particles and patterned surfaces. Depletion interaction induced aggregation of PEG-CNTs may provide a method to place PEG-CNTs on a specific position for different applications ranging from biomedical to industrial usages.

A quantitative assessment of volumetric and anatomic changes of the parotid gland during intensity-modulated radiotherapy for head and neck cancer using serial computed tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ajani, Abdallah A.; Qureshi, Muhammad M.; Kovalchuk, Nataliya

To evaluate the change in volume and movement of the parotid gland measured by serial contrast-enhanced computed tomography scans in patients with head and neck cancer treated with parotid-sparing intensity-modulated radiotherapy (IMRT). A prospective study was performed on 13 patients with head and neck cancer undergoing dose-painted IMRT to 69.96 Gy in 33 fractions. Serial computed tomography scans were performed at baseline, weeks 2, 4, and 6 of radiotherapy (RT), and at 6 weeks post-RT. The parotid volume was contoured at each scan, and the movement of the medial and lateral borders was measured. The patient's body weight was recordedmore » at each corresponding week during RT. Regression analyses were performed to ascertain the rate of change during treatment as a percent change per fraction in parotid volume and distance relative to baseline. The mean parotid volume decreased by 37.3% from baseline to week 6 of RT. The overall rate of change in parotid volume during RT was−1.30% per fraction (−1.67% and−0.91% per fraction in≥31 Gy and<31 Gy mean planned parotid dose groups, respectively, p = 0.0004). The movement of parotid borders was greater in the≥31 Gy mean parotid dose group compared with the<31 Gy group (0.22% per fraction and 0.14% per fraction for the lateral border and 0.19% per fraction and 0.06% per fraction for the medial border, respectively). The median change in body weight was−7.4% (range, 0.75% to−17.5%) during RT. A positive correlation was noted between change in body weight and parotid volume during the course of RT (Spearman correlation coefficient, r = 0.66, p<0.01). Head and neck IMRT results in a volume loss of the parotid gland, which is related to the planned parotid dose, and the patient's weight loss during RT.« less

A new sample treatment for asialo-Tf determination with capillary electrophoresis: an added value to the analysis of CDT.

PubMed

Porpiglia, Nadia Maria; De Palo, Elio Franco; Savchuk, Sergey Alexandrovich; Appolonova, Svetlana Alexandrovna; Bortolotti, Federica; Tagliaro, Franco

2018-05-10

The non-glycosylated glycoform of transferrin (Tf), known as asialo-Tf, was not selected (in favor of disialo-Tf) as the measurand for the standardization of carbohydrate deficient transferrin (CDT) determination because of a lower diagnostic sensitivity provided with the currently available analytical procedures for sera. However, asialo-Tf could provide an additional value to disialo-Tf in the CDT analysis employed in forensic toxicology contexts. The present work aimed at developing an easy sample preparation based on PEG precipitation in order to improve the detectability of asialo-Tf in capillary electrophoresis (CE). Equal volumes (35 μL) of serum and of 30% PEG-8000 were mixed and briefly vortexed. After centrifugation, the supernatant was iron saturated with a ferric solution (1:1, v/v). The mixture was analyzed in CE for asialo-Tf and disialo-Tf determination. PEG-8000 precipitation allowed the improvement of the baseline in the electropherograms in terms of interferences reduction particularly in the asialo-Tf migration region. The detection of asialo-Tf was possible in 89% of samples with disialo-Tf above the cut-off limit, whereas only 16% of them showed asialo-Tf by employing the traditional sample preteatment. Asialo-Tf represents an additional value to disialo-Tf as a biomarker of alcohol abuse in forensic toxicology. Copyright © 2018. Published by Elsevier B.V.

Acoustic, Thermal and Molecular Interactions of Polyethylene Glycol (2000, 3000, 6000)

NASA Astrophysics Data System (ADS)

Venkatramanan, K.; Padmanaban, R.; Arumugam, V.

Polyethylene Glycol (PEG) is a condensation polymer of ethylene oxide and water. PEG find its application as emulsifying agents, detergents, soaps, plasticizers, ointments, etc. Though the chemical and physical properties of PEG are known, still because of their uses in day to day life, it becomes necessary to study few physical properties like ultrasonic velocity, viscosity and hence adiabatic compressibility, free length, etc. In the present study, an attempt has been made to compute the activation energy and hence to analyse the molecular interactions of aqueous solutions of Polyethylene Glycol of molar mass 2000, 3000 and 6000 at different concentrations (2%, 4%, 6%, 8% and 10%) at different temperatures (303K, 308K, 313K, 318K) by determining relative viscosity, ultrasonic velocity and density. Various parameters like adiabatic compressibility, viscous relaxation time, inter molecular free length, free volume, internal pressure, etc are calculated at 303K and the results are discussed in the light of polymer-solvent interaction. This study helps to understand the behavior of macro-molecules with respect to changing concentration and temperature. Furthermore, viscosity and activation energy results are correlated to understand the increased entanglement of the polymer chains due to the increase in the concentration of a polymer solution that leads to an increase in viscosity and an increase in the activation energy of viscous flow.

Change in Seroma Volume During Whole-Breast Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sharma, Rajiv; Spierer, Marnee; Mutyala, Subhakar

2009-09-01

Purpose: After breast-conserving surgery, a seroma often forms in the surgical cavity. If not drained, it may affect the volume of tumor bed requiring a boost after whole-breast radiation therapy (WBRT). Our objective was to evaluate the change in seroma volume that occurs during WBRT, before boost planning. Methods and Materials: A retrospective review was performed of women receiving breast-conserving therapy with evidence of seroma at the time of WBRT planning. Computed tomography (CT) simulation was performed before WBRT and before the tumor bed boost. All patients received either a hypofractionated (42.4 Gy/16 fraction + 9.6 Gy/4 fraction boost) ormore » standard fractionated (50.4 Gy/28 fraction + 10 Gy/5 fraction boost) regimen. Seroma volumes were contoured and compared on CT at the time of WBRT simulation and tumor bed boost planning. Results: Twenty-four patients with evidence of seroma were identified and all patients received WBRT without drainage of the seroma. Mean seroma volume before WBRT and at boost planning were significantly different at 65.7 cm{sup 3} (SD, 50.5 cm{sup 3}) and 35.6 cm{sup 3} (SD, 24.8 cm{sup 3}), respectively (p < 0.001). Mean and median reduction in seroma volume during radiation were 39.6% (SD, 23.8%) and 46.2% (range, 10.7-76.7%), respectively. Fractionation schedule was not correlated with change in seroma volume. Length of time from surgery to start of radiation therapy showed an inverse correlation with change in seroma volume (Pearson correlation r = -0.53, p < 0.01). Conclusions: The volume of seroma changes significantly during WBRT. Consequently, the accuracy of breast boost planning is likely affected, as is the volume of normal breast tissue irradiated. CT-based boost planning before boost irradiation is suggested to ensure appropriate coverage.« less

Identification of Poly(ethylene glycol) and Poly(ethylene glycol)-Based Detergents Using Peptide Search Engines.

PubMed

Ahmadi, Shiva; Winter, Dominic

2018-06-05

Poly(ethylene glycol) (PEG) is one of the most common polymer contaminations in mass spectrometry (MS) samples. At present, the detection of PEG and other polymers relies largely on manual inspection of raw data, which is laborious and frequently difficult due to sample complexity and retention characteristics of polymer species in reversed-phase chromatography. We developed a new strategy for the automated identification of PEG molecules from tandem mass spectrometry (MS/MS) data using protein identification algorithms in combination with a database containing "PEG-proteins". Through definition of variable modifications, we extend the approach for the identification of commonly used PEG-based detergents. We exemplify the identification of different types of polymers by static nanoelectrospray tandem mass spectrometry (nanoESI-MS/MS) analysis of pure detergent solutions and data analysis using Mascot. Analysis of liquid chromatography-tandem mass spectrometry (LC-MS/MS) runs of a PEG-contaminated sample by Mascot identified 806 PEG spectra originating from four PEG species using a defined set of modifications covering PEG and common PEG-based detergents. Further characterization of the sample for unidentified PEG species using error-tolerant and mass-tolerant searches resulted in identification of 3409 and 3187 PEG-related MS/MS spectra, respectively. We further demonstrate the applicability of the strategy for Protein Pilot and MaxQuant.

Plasma-mediated grafting of poly(ethylene glycol) on polyamide and polyester surfaces and evaluation of antifouling ability of modified substrates.

PubMed

Dong, Baiyan; Jiang, Hongquan; Manolache, Sorin; Wong, Amy C Lee; Denes, Ferencz S

2007-06-19

A simple cold plasma technique was developed to functionalize the surfaces of polyamide (PA) and polyester (PET) for the grafting of polyethylene glycol (PEG) with the aim of reducing biofilm formation. The surfaces of PA and PET were treated with silicon tetrachloride (SiCl4) plasma, and PEG was grafted onto plasma-functionalized substrates (PA-PEG, PET-PEG). Different molecular weights of PEG and grafting times were tested to obtain optimal surface coverage by PEG as monitored by electron spectroscopy for chemical analysis (ESCA). The presence of a predominant C-O peak on the PEG-modified substrates indicated that the grafting was successful. Data from hydroxyl group derivatization and water contact angle measurement also indicated the presence of PEG after grafting. The PEG-grafted PA and PET under optimal conditions had similar chemical composition and hydrophilicity; however, different morphology changes were observed after grafting. Both PA-PEG and PET-PEG surfaces developed under optimal plasma conditions showed about 96% reduction in biofilm formation by Listeria monocytogenes compared with that of the corresponding unmodified substrates. This plasma functionalization method provided an efficient way to graft PEG onto PA and PET surfaces. Because of the high reactivity of Si-Cl species, this method could potentially be applied to other polymeric materials.

Identification of the Centrifuged Lipoaspirate Fractions Suitable for Postgrafting Survival.

PubMed

Qiu, Lihong; Su, Yingjun; Zhang, Dongliang; Song, Yajuan; Liu, Bei; Yu, Zhou; Guo, Shuzhong; Yi, Chenggang

2016-01-01

The Coleman centrifugation procedure generates fractions with different adipocyte and progenitor cell densities. This study aimed to identify all fractions that are feasible for implantation. Human lipoaspirates were processed by Coleman centrifugation. The centrifugates were divided arbitrarily into upper, middle, and lower layers. Adipocyte viability, morphology, numbers of stromal vascular fraction cells, and adipose-derived mesenchymal stem cells of each layer were determined. The 12-week volume retention of subcutaneously implanted 0.3-ml lipoasperate of each layer was investigated in an athymic mice model. Most damaged adipocytes were located in the upper layers, whereas the intact adipocytes were distributed in the middle and lower layers. A gradient of stromal vascular fraction cell density was formed in the centrifugates. The implant volume retentions of samples from the upper, middle, and lower layers were 33.44 ± 5.9, 55.11 ± 4.4, and 71.2 ± 5.8 percent, respectively. Furthermore, the middle and lower layers contained significantly more adipose-derived stem cells than did the upper layer. The lower layer contains more viable adipocytes and stromal vascular fraction cells leading to the highest implant volume retention, whereas the most impaired cells are distributed in the upper layer, leading to the least volume retention. Although with a lower stromal vascular fraction content, the middle layer has a substantial number of intact adipocytes that are capable of retaining partial adipose tissue volume after implantation, suggesting that the middle layer may be an alternative fat source when large volumes of fat grafts are needed for transplantation.

Polyethylene glycol-coated blue-emitting silicon dots with improved properties for uses in aqueous and biological environments

NASA Astrophysics Data System (ADS)

Rodríguez Sartori, Damián; Lillo, Cristian R.; Romero, Juan J.; Dell‧Arciprete, María Laura; Miñán, Alejandro; de Mele, Mónica Fernández Lorenzo; Gonzalez, Mónica C.

2016-11-01

Grafting of polyethylene glycol (PEG) to ultrasmall photoluminescent silicon dots (SiDs) is expected to improve and expand the applications of these particles to aqueous environments and biological systems. Herein we report a novel one-pot synthesis of robust, highly water compatible PEG-coated SiDs (denoted as PEG-SiDs) of (3.3 ± 0.5) nm size. The nanoparticles’ synthesis is based on the liquid phase oxidation of magnesium silicide using PEG as reaction media and leading to high PEG density grafting. PEG-SiDs enhanced photophysical, photosensitising, and solution properties in aqueous environments are described and compared to those of 2 nm size PEG-coated SiDs with low PEG density grafting (denoted as PEG-NHSiDs) obtained from a multistep synthesis strategy. PEG-SiDs form highly dispersed suspensions in water showing stable photoluminescence and quantum yields of Φ = 0.13 ± 0.04 at 370 nm excitation in air-saturated suspensions. These particles exhibited the capacity of photosensitising the formation of singlet molecular oxygen, not observed for PEG-NHSiDs. PEG robust shielding of the silicon core luminescent properties is further demonstrated in bio-imaging experiments stressing the strong interaction between PEG-SiDs and Staphylococcus aureus smears by observing the photoluminescence of particles. PEG-SiDs were found to be nontoxic to S. aureus cells at concentrations of 100 mg ml-1, though a bacteriostatic effect on S. aureus biofilms was observed upon UV-A irradiation under conditions where light alone has no effect.

Antitumor Effect of GO-PEG-DOX Complex on EMT-6 Mouse Breast Cancer Cells.

PubMed

Yan, Jinyin; Song, Bo; Hu, Wanning; Meng, Ying; Niu, Fengling; Han, Xiaochen; Ge, Yuhui; Li, Ning

2018-05-01

Doxorubicin (DOX) can be used to treat malignant tumors, but with multiple adverse effects. Graphene oxide-polyethylene glycol (GO-PEG) is a novel nanoscale carrier material and can elevate solubility and biocompatibility of drugs. This study prepared a GO-PEG-DOX complex, whose toxicity and antitumor effects were evaluated on mouse EMT-6 breast cancer cells. GO-PEG-DOX complex was prepared for calculating the drug carrier rate of DOX on GO-PEG by MV approach. EMT-6 cells were treated with 40 μg/mL GO-PEG, 1 μg/mL DOX, or 40 μg/mL +1 μg/mL GO-PEG-DOX for 72 h of incubation. Cells without treatment were considered the control group. Cell survival rate and apoptotic rate were tested at different time points. GO-PEG and GO-PEG-DOX complex were successfully prepared with satisfactory solubility. After 72 h of incubation, EMT-6 cells after GO-PEG-DOX treatment had significantly higher survival rate than GO-PEG group (p < 0.05). All three treatment groups had significantly elevated apoptotic rates than control group (p < 0.05). GO-PEG-DOX group had much more apoptosis (p < 0.05 compared with DOX group). Moreover, with elongated treatment time, all groups showed decreased survival rate (p < 0.05). GO-PEG did not reduce the cytotoxicity of DOX on EMT-6 cells. GO-PEG-DOX complex can increase the water solubility and targeting sensitivity of DOX, with facilitating effects on DOX-induced tumor cell apoptosis.

Intra-fraction motion of larynx radiotherapy

NASA Astrophysics Data System (ADS)

Durmus, Ismail Faruk; Tas, Bora

2018-02-01

In early stage laryngeal radiotherapy, movement is an important factor. Thyroid cartilage can move from swallowing, breathing, sound and reflexes. The effects of this motion on the target volume (PTV) during treatment were examined. In our study, the target volume movement during the treatment for this purpose was examined. Thus, setup margins are re-evaluated and patient-based PTV margins are determined. Intrafraction CBCT was scanned in 246 fractions for 14 patients. During the treatment, the amount of deviation which could be lateral, vertical and longitudinal axis was determined. ≤ ± 0.1cm deviation; 237 fractions in the lateral direction, 202 fractions in the longitudinal direction, 185 fractions in the vertical direction. The maximum deviation values were found in the longitudinal direction. Intrafraction guide in laryngeal radiotherapy; we are sure of the correctness of the treatment, the target volume is to adjust the margin and dose more precisely, we control the maximum deviation of the target volume for each fraction. Although the image quality of intrafraction-CBCT scans was lower than the image quality of planning CT, they showed sufficient contrast for this work.

Performance enhancement of direct ethanol fuel cell using Nafion composites with high volume fraction of titania

NASA Astrophysics Data System (ADS)

Matos, B. R.; Isidoro, R. A.; Santiago, E. I.; Fonseca, F. C.

2014-12-01

The present study reports on the performance enhancement of direct ethanol fuel cell (DEFC) at 130 °C with Nafion-titania composite electrolytes prepared by sol-gel technique and containing high volume fractions of the ceramic phase. It is found that for high volume fractions of titania (>10 vol%) the ethanol uptake of composites is largely reduced while the proton conductivity at high-temperatures is weakly dependent on the titania content. Such tradeoff between alcohol uptake and conductivity resulted in a boost of DEFC performance at high temperatures using Nafion-titania composites with high fraction of the inorganic phase.

Comparison of polyethylene glycol with and without electrolytes in the treatment of constipation in elderly institutionalized patients: a randomized, double-blind, parallel-group study.

PubMed

Seinelä, Lauri; Sairanen, Ulla; Laine, Tarmo; Kurl, Sangita; Pettersson, Tiina; Happonen, Pertti

2009-01-01

Polyethylene glycol (PEG) is a commonly used osmotic laxative. PEG with electrolytes is mixed with water, but PEG without electrolytes can also be mixed with, for example, juice, coffee or tea, making it more palatable. Laxatives, including PEG, are commonly used by the elderly, particularly those living in institutions. Few clinical studies, however, have investigated the use of PEG in this population. To test whether PEG 4000 without electrolytes (hypotonic PEG) is at least as effective and safe as PEG 4000 with electrolytes (isotonic PEG) in elderly institutionalized constipated patients. The acceptability of the treatments was also compared. This randomized, double-blind, parallel-group study was conducted at ten private assisted-living facilities or communal nursing homes in Finland. Eligible patients were required to have used isotonic PEG at a stable dose without any other treatment for constipation (except for Plantago ovata seeds) for at least 2 weeks prior to a run-in period. After the 1-week run-in, 62 patients (mean age 86 years; range 66-99 years) were randomly either switched to receive hypotonic PEG or continued to receive isotonic PEG, both dissolved in water, 12 g once or twice daily or once every other day, for 4 weeks. Stool frequency, stool consistency, stool straining and gastrointestinal symptoms were recorded. Safety laboratory tests were conducted before and after the treatment period. Acceptability was assessed at the end of the study. At week 4, mean (SD) weekly stool frequencies in the hypotonic and isotonic PEG groups were 8.5 (4.5) and 8.4 (3.6), respectively. The mean stool frequency ratio (95% CI) was 0.90 (0.74, 1.10); thus, the PEG products were considered equally effective. At week 4, the proportion of patients with soft or normal stool consistency was higher in the hypotonic PEG group than in the isotonic PEG group (70% vs 52%), but this difference was not statistically significant. There were no differences between the groups in stool straining or gastrointestinal symptoms. In the safety laboratory tests, no clinically significant differences between the groups were detected, although plasma sodium level was statistically significantly lower in the hypotonic PEG group at the end of the study (137.7 vs 138.9 mmol/L, respectively; p = 0.012). Most patients were willing to continue their study treatment (85% in the hypotonic PEG and 63% in the isotonic PEG group; p = 0.070). Compared with only 12% of the patients receiving hypotonic PEG, however, 31% of the patients in the isotonic PEG group rated the taste of the study treatment as bad or very bad (p = 0.101). Hypotonic PEG solution is as effective as isotonic PEG in the treatment of constipation in elderly institutionalized patients. Both treatments appear safe, well tolerated and, when dissolved in water, well accepted by the majority of the patients. When desired, switching from isotonic to hypotonic PEG can safely take place in elderly individuals without compromising efficacy.

Improved lignin polyurethane properties with Lewis acid treatment.

PubMed

Chung, Hoyong; Washburn, Newell R

2012-06-27

Chemical modification strategies to improve the mechanical properties of lignin-based polyurethanes are presented. We hypothesized that treatment of lignin with Lewis acids would increase the concentration of hydroxyl groups available to react with diisocyanate monomers. Under the conditions used, hydrogen bromide-catalyzed modification resulted in a 28% increase in hydroxyl group content. Associated increases in hydrophilicity of solvent-cast thin films were also recorded as evidenced by decreases in water contact angle. Polyurethanes were then prepared by first preparing a prepolymer based on mixtures of toluene-2,4-diisocyanate (TDI) and unmodified or modified lignin, then polymerization was completed through addition of polyethylene glycol (PEG), resulting in mass ratios of TDI:lignin:PEG of 43:17:40 in the compositions investigated here. The mixture of TDI and unmodified lignin resulted in a lignin powder at the bottom of the liquid, suggesting it did not react directly with TDI. However, a homogeneous solution resulted when TDI and the hydrogen bromide-treated lignin were mixed, suggesting demethylation indeed increased reactivity and resulted in better integration of lignin into the urethane network. Significant improvements in mechanical properties of modified lignin polyurethanes were observed, with a 6.5-fold increase in modulus, which were attributed to better integration of the modified lignin into the covalent polymer network due to the higher concentration of hydroxyl groups. This research indicates that chemical modification strategies can lead to significant improvements in the properties of lignin-based polymeric materials using a higher fraction of an inexpensive lignin monomer from renewable resources and a lower fraction an expensive, petroleum-derived isocyanate monomer to achieve the required material properties.

Cost analysis of cetuximab (Erbitux) plus radiotherapy (ERT) versus concomitant cisplatin plus radiotherapy (CRT) within an NHS oncology unit (single institution): a pilot study.

PubMed

Caroline, Brammer; Sundus, Yahya; Dawn, Dawson; Carol, Glaister; Susan, Merrick

2016-12-01

The aim of this feasibility study is to define the resource effectiveness of cetuximab vs cisplatin given concomitantly with radiotherapy for squamous cell carcinoma within a National Health Service clinical oncology unit. 20 patients with Stage 3 or 4 head and neck squamous cell cancers were randomized to receive either cetuximab with radiotherapy (ERT) or cisplatin with radiotherapy concurrent with external beam radiotherapy 70 Gy in 35 fractions on a 1 : 1 basis over a 12-month duration. The study compared the resource utilization of ERT vs cisplatin with radiotherapy taking into account drug costs, clinical management and the costs of managing treatment-related toxicity from first fraction of radiotherapy to 6 months after the completion of therapy. Outcome measures were quality of life (recorded at the entry, end of radiotherapy, 6 weeks post treatment and 6 months post treatment), admissions to hospital, delays to radiotherapy, locoregional control and survival. Total drug costs including cost of nutritional supplements for patients treated with cetuximab were £7407.45 compared with £3959.07 for patients treated with cisplatin. Unscheduled admissions for toxicity management were significantly more common in the ERT arm. Healthcare personnel spent significantly more time delivering unscheduled outpatient care for patients receiving cisplatin than for those receiving cetuximab (p = 0.01). No significant difference in the quality of life was suggested at baseline, 6 weeks and 6 months. The mean time to removal of percutaneous gastrostomy (PEG) after completion of radiotherapy was 49.7 weeks in the cisplatin arm and 18.5 weeks in the cetuximab arm (p = 0.04). There was a statistically significant difference in patient-reported use of PEG between the cisplatin and cetuximab arms at 6 months following completion of treatment (p = 0.04). At 21 months, overall survival was 80% in the cisplatin arm vs 50% in the cetuximab (p = 0.332), with disease-free survival being 80% in the cisplatin arm vs 40% in the cetuximab (p = 0.097). Cetuximab is still more expensive in simple drug cost terms than cisplatin when delivered with radiotherapy taking into account costs of drugs for toxicity management and nutritional supplements but other resource implications such as inpatient admission, time spent delivering unscheduled care and cost of additional investigations to manage toxicity for patients treated with cisplatin significantly reduce differential. The study suggested significant differences in patient-reported PEG use at 6 months and in time to PEG removal in favour of the cetuximab arm. Advances in knowledge: There is paucity of randomized data on cost analysis for cisplatin vs cetuximab radiotherapy; this trial informs on the cost analysis between the two approaches.

Raman scattering studies on PEG functionalized hydroxyapatite nanoparticles

NASA Astrophysics Data System (ADS)

Yamini, D.; Devanand Venkatasubbu, G.; Kumar, J.; Ramakrishnan, V.

2014-01-01

The pure hydroxyapatite (HAP) nanoparticles (NPs) have been synthesized by wet chemical precipitation method. Raman spectral measurements have been made for pure HAP, pure Polyethylene glycol (PEG) 6000 and PEG coated HAP in different mass ratios (sample 1, sample 2 and sample 3). The peaks observed in Raman spectrum of pure HAP and the XRD pattern have confirmed the formation of HAP NPs. Vibrational modes have been assigned for pure HAP and pure PEG 6000. The observed variation in peak position of Raman active vibrational modes of PEG in PEG coated HAP has been elucidated in this work, in terms of intermolecular interactions between PEG and HAP. Further these results suggest that the functionalization of nanoparticles may be independent of PEG mass.

Use of amphiphilic triblock copolymers for enhancing removal efficiency of organic pollutant from contaminated media

NASA Astrophysics Data System (ADS)

Lee, Jun Hyup; Lee, Byungsun; Son, Intae; Kim, Jae Hong; Kim, Chunho; Yoo, Ji Yong; Wu, Jong-Pyo; Kim, Younguk

2015-11-01

We have studied amphiphilic triblock copolymers poly(ethylene glycol)- b-poly(propylene glycol)- b-poly(ethylene glycol) (PEG- b-PPG- b-PEG) and poly(propylene glycol)- b-poly(ethylene glycol)- b-poly(propylene glycol) (PPG- b-PEG- b-PPG) as possible substitutes for sodium dodecyl sulfate as anionic surfactants for the removal of hydrophobic contaminants. The triblock copolymers were compared with sodium dodecyl sulfate in terms of their abilities to remove toluene as hydrophobic contaminant in fuel, and the effects of polymer structure, PEG content, and concentration were studied. The PEG- b-PPG- b-PEG copolymer containing two hydrophilic PEG blocks was more effective for the removal of hydrophobic contaminant at extremely high concentration. We also measured the removal capabilities of the triblock copolymers having various PEG contents and confirmed that removal capability was greatest at 10% PEG content regardless of polymer structure. As with sodium dodecyl sulfate, the removal efficiency of a copolymer has a positive correlation with its concentration. Finally, we proposed the amphiphilic triblock copolymer of PPG- b-PEG- b-PPG bearing 10% PEG content that proved to be the most effective substitute for sodium dodecyl sulfate.

Lamellar, micro-phase separated blends of methyl cellulose and dendritic polyethylene glycol, POSS-PEG.

PubMed

Chinnam, Parameswara Rao; Mantravadi, Ramya; Jimenez, Jayvic C; Dikin, Dmitriy A; Wunder, Stephanie L

2016-01-20

Blends of methyl cellulose (MC) and liquid pegylated polyoctahedralsilsesquioxane (POSS-PEG) were prepared from non-gelled, aqueous solutions at room temperature (RT), which was below their gel temperatures (Tm). Lamellar, fibrillated films (pure MC) and increasingly micro-porous morphologies with increasing POSS-PEG content were formed, which had RT moduli between 1 and 5GPa. Evidence of distinct micro-phase separated MC and POSS-PEG domains was indicated by the persistence of the MC and POSS-PEG (at 77K) crystal structures in the X-ray diffraction data, and scanning transmission electron images. Mixing of MC and POSS-PEG in the interface region was indicated by suppression of crystallinity in the POSS-PEG, and increases/decreases in the glass transition temperatures (Tg) of POSS-PEG/MC in the blends compared with the pure components. These interface interactions may serve as cross-link sites between the micro-phase separated domains that permit incorporation of high amounts of POSS-PEG in the blends, prevent macro-phase separation and result in rubbery material properties (at high POSS-PEG content). Above Tg/Tm of POSS-PEG, the moduli of the blends increase with MC content as expected. However, below Tg/Tm of POSS-PEG, the moduli are greater for blends with high POSS-PEG content, suggesting that it behaves like semi-crystalline polyethylene oxide reinforced with silica (SiO1.5). Copyright © 2015 Elsevier Ltd. All rights reserved.

Doxorubicin-loaded micelles based on multiarm star-shaped PLGA-PEG block copolymers: influence of arm numbers on drug delivery.

PubMed

Ma, Guilei; Zhang, Chao; Zhang, Linhua; Sun, Hongfan; Song, Cunxian; Wang, Chun; Kong, Deling

2016-01-01

Star-shaped block copolymers based on poly(D,L-lactide-co-glycolide) (PLGA) and poly(ethylene glycol) (PEG) (st-PLGA-PEG) were synthesized with structural variation on arm numbers in order to investigate the relationship between the arm numbers of st-PLGA-PEG copolymers and their micelle properties. st-PLGA-PEG copolymers with arm numbers 3, 4 and 6 were synthesized by using different cores such as trimethylolpropane, pentaerythritol and dipentaerythritol, and were characterized by nuclear magnetic resonance and gel permeation chromatography. The critical micelle concentration decreased with increasing arm numbers in st-PLGA-PEG copolymers. The doxorubicin-loaded st-PLGA-PEG micelles were prepared by a modified nanoprecipitation method. Micellar properties such as particle size, drug loading content and in vitro drug release behavior were investigated as a function of the number of arms and compared with each other. The doxorubicin-loaded 4-arm PLGA-PEG micelles were found to have the highest cellular uptake efficiency and cytotoxicity compared with 3-arm PLGA-PEG micelles and 6-arm PLGA-PEG micelles. The results suggest that structural tailoring of arm numbers from st-PLGA-PEG copolymers could provide a new strategy for designing drug carriers of high efficiency. Structural tailoring of arm numbers from star shaped-PLGA-PEG copolymers (3-arm/4-arm/6-arm-PLGA-PEG) could provide a new strategy for designing drug carriers of high efficiency.

Regulating the surface poly(ethylene glycol) density of polymeric nanoparticles and evaluating its role in drug delivery in vivo.

PubMed

Du, Xiao-Jiao; Wang, Ji-Long; Liu, Wei-Wei; Yang, Jin-Xian; Sun, Chun-Yang; Sun, Rong; Li, Hong-Jun; Shen, Song; Luo, Ying-Li; Ye, Xiao-Dong; Zhu, Yan-Hua; Yang, Xian-Zhu; Wang, Jun

2015-11-01

Poly(ethylene glycol) (PEG) is usually used to protect nanoparticles from rapid clearance in blood. The effects are highly dependent on the surface PEG density of nanoparticles. However, there lacks a detailed and informative study in PEG density and in vivo drug delivery due to the critical techniques to precisely control the surface PEG density when maintaining other nano-properties. Here, we regulated the polymeric nanoparticles' size and surface PEG density by incorporating poly(ε-caprolactone) (PCL) homopolymer into poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-PCL) and adjusting the mass ratio of PCL to PEG-PCL during the nanoparticles preparation. We further developed a library of polymeric nanoparticles with different but controllable sizes and surface PEG densities by changing the molecular weight of the PCL block in PEG-PCL and tuning the molar ratio of repeating units of PCL (CL) to that of PEG (EG). We thus obtained a group of nanoparticles with variable surface PEG densities but with other nano-properties identical, and investigated the effects of surface PEG densities on the biological behaviors of nanoparticles in mice. We found that, high surface PEG density made the nanoparticles resistant to absorption of serum protein and uptake by macrophages, leading to a greater accumulation of nanoparticles in tumor tissue, which recuperated the defects of decreased internalization by tumor cells, resulting in superior antitumor efficacy when carrying docetaxel. Copyright © 2015 Elsevier Ltd. All rights reserved.

Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (ε-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone

PubMed Central

Liu, Jinsong; Zeng, Youyun; Shi, Shuai; Xu, Lihua; Zhang, Hualin; Pathak, Janak L; Pan, Yihuai

2017-01-01

Treatment of cancer metastasized to bone is still a challenge due to hydrophobicity, instability, and lack of target specificity of anticancer drugs. Poly (ethylene glycol)-poly (ε-caprolactone) polymer (PEG-PCL) is an effective, biodegradable, and biocompatible hydrophobic drug carrier, but lacks bone specificity. Polyaspartic acid with eight peptide sequences, that is, (Asp)8, has a strong affinity to bone surface. The aim of this study was to synthesize (Asp)8-PEG-PCL nanoparticles as a bone-specific carrier of hydrophobic drugs to treat cancer metastasized to bone. 1H nuclear magnetic resonance, Fourier transform infrared spectroscopy, and transmission electron microscopy data showed that (Asp)8-PEG-PCL nanoparticles (size 100 nm) were synthesized successfully. (Asp)8-PEG-PCL nanoparticles did not promote erythrocyte aggregation. Fluorescence microscopy showed clear uptake of Nile red-loaded (Asp)8-PEG-PCL nanoparticles by cancer cells. (Asp)8-PEG-PCL nanoparticles did not show cytotoxic effect on MG63 and human umbilical vein endothelial cells at the concentration of 10–800 μg/mL. (Asp)8-PEG-PCL nanoparticles bound with hydroxyapatite 2-fold more than PEG-PCL. Intravenously injected (Asp)8-PEG-PCL nanoparticles accumulated 2.7-fold more on mice tibial bone, in comparison to PEG-PCL. Curcumin is a hydrophobic anticancer drug with bone anabolic properties. Curcumin was loaded in the (Asp)8-PEG-PCL. (Asp)8-PEG-PCL showed 11.07% loading capacity and 95.91% encapsulation efficiency of curcumin. The curcumin-loaded (Asp)8-PEG-PCL nanoparticles gave sustained release of curcumin in high dose for >8 days. The curcumin-loaded (Asp)8-PEG-PCL nanoparticles showed strong antitumorigenic effect on MG63, MCF7, and HeLa cancer cells. In conclusion, (Asp)8-PEG-PCL nanoparticles were biocompatible, permeable in cells, a potent carrier, and an efficient releaser of hydrophobic anticancer drug and were bone specific. The curcumin-loaded (Asp)8-PEG-PCL nanoparticles showed strong antitumorigenic ability in vitro. Therefore, (Asp)8-PEG-PCL nanoparticles could be a potent carrier of hydrophobic anticancer drugs to treat the cancer metastasized to bone. PMID:28507436

Single endoscopist-performed percutaneous endoscopic gastrostomy tube placement.

PubMed

Erdogan, Askin

2013-07-14

To investigate whether single endoscopist-performed percutaneous endoscopic gastrostomy (PEG) is safe and to compare the complications of PEG with those reported in the literature. Patients who underwent PEG placement between June 2001 and August 2011 at the Baskent University Alanya Teaching and Research Center were evaluated retrospectively. Patients whose PEG was placed for the first time by a single endoscopist were enrolled in the study. PEG was performed using the pull method. All of the patients were evaluated for their indications for PEG, major and minor complications resulting from PEG, nutritional status, C-reactive protein (CRP) levels and the use of antibiotic treatment or antibiotic prophylaxis prior to PEG. Comorbidities, rates, time and reasons for mortality were also evaluated. The reasons for PEG removal and PEG duration were also investigated. Sixty-two patients underwent the PEG procedure for the first time during this study. Eight patients who underwent PEG placement by 2 endoscopists were not enrolled in the study. A total of 54 patients were investigated. The patients' mean age was 69.9 years. The most common indication for PEG was cerebral infarct, which occurred in approximately two-thirds of the patients. The mean albumin level was 3.04 ± 0.7 g/dL, and 76.2% of the patients' albumin levels were below the normal values. The mean CRP level was high in 90.6% of patients prior to the procedure. Approximately two-thirds of the patients received antibiotics for either prophylaxis or treatment for infections prior to the PEG procedure. Mortality was not related to the procedure in any of the patients. Buried bumper syndrome was the only major complication, and it occurred in the third year. In such case, the PEG was removed and a new PEG tube was placed via surgery. Eight patients (15.1%) experienced minor complications, 6 (11.1%) of which were wound infections. All wound infections except one recovered with antibiotic treatment. Two patients had bleeding from the PEG site, one was resolved with primary suturing and the other with fresh frozen plasma transfusion. The incidence of major and minor complications is in keeping with literature. This finding may be noteworthy, especially in developing countries.

Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (ε-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone.

PubMed

Liu, Jinsong; Zeng, Youyun; Shi, Shuai; Xu, Lihua; Zhang, Hualin; Pathak, Janak L; Pan, Yihuai

2017-01-01

Treatment of cancer metastasized to bone is still a challenge due to hydrophobicity, instability, and lack of target specificity of anticancer drugs. Poly (ethylene glycol)-poly (ε-caprolactone) polymer (PEG-PCL) is an effective, biodegradable, and biocompatible hydrophobic drug carrier, but lacks bone specificity. Polyaspartic acid with eight peptide sequences, that is, (Asp) 8 , has a strong affinity to bone surface. The aim of this study was to synthesize (Asp) 8 -PEG-PCL nanoparticles as a bone-specific carrier of hydrophobic drugs to treat cancer metastasized to bone. 1 H nuclear magnetic resonance, Fourier transform infrared spectroscopy, and transmission electron microscopy data showed that (Asp) 8 -PEG-PCL nanoparticles (size 100 nm) were synthesized successfully. (Asp) 8 -PEG-PCL nanoparticles did not promote erythrocyte aggregation. Fluorescence microscopy showed clear uptake of Nile red-loaded (Asp) 8 -PEG-PCL nanoparticles by cancer cells. (Asp) 8 -PEG-PCL nanoparticles did not show cytotoxic effect on MG63 and human umbilical vein endothelial cells at the concentration of 10-800 μg/mL. (Asp) 8 -PEG-PCL nanoparticles bound with hydroxyapatite 2-fold more than PEG-PCL. Intravenously injected (Asp) 8 -PEG-PCL nanoparticles accumulated 2.7-fold more on mice tibial bone, in comparison to PEG-PCL. Curcumin is a hydrophobic anticancer drug with bone anabolic properties. Curcumin was loaded in the (Asp) 8 -PEG-PCL. (Asp) 8 -PEG-PCL showed 11.07% loading capacity and 95.91% encapsulation efficiency of curcumin. The curcumin-loaded (Asp) 8 -PEG-PCL nanoparticles gave sustained release of curcumin in high dose for >8 days. The curcumin-loaded (Asp) 8 -PEG-PCL nanoparticles showed strong antitumorigenic effect on MG63, MCF7, and HeLa cancer cells. In conclusion, (Asp) 8 -PEG-PCL nanoparticles were biocompatible, permeable in cells, a potent carrier, and an efficient releaser of hydrophobic anticancer drug and were bone specific. The curcumin-loaded (Asp) 8 -PEG-PCL nanoparticles showed strong antitumorigenic ability in vitro. Therefore, (Asp) 8 -PEG-PCL nanoparticles could be a potent carrier of hydrophobic anticancer drugs to treat the cancer metastasized to bone.

Pharmacokinetic evidence for improved ophthalmic drug delivery by reduction of instilled volume.

PubMed

Patton, T F

1977-07-01

The bioavailability of topically applied pilocarpine nitrate was studied as a function of instilled volume. As the instilled volume decreased, the fraction of dose absorbed increased. The relationship between fraction absorbed and instilled volume was not direct, but appropriate adjustment of instilled volume and concentration should permit substantial dosage reductions without sacrifice of drug concentration in the eye. The implications of these findings from both a therapeutic and toxicity standpoint are discussed.

Quantitative assessment of fatty infiltration and muscle volume of the rotator cuff muscles using 3-dimensional 2-point Dixon magnetic resonance imaging.

PubMed

Matsumura, Noboru; Oguro, Sota; Okuda, Shigeo; Jinzaki, Masahiro; Matsumoto, Morio; Nakamura, Masaya; Nagura, Takeo

2017-10-01

In patients with rotator cuff tears, muscle degeneration is known to be a predictor of irreparable tears and poor outcomes after surgical repair. Fatty infiltration and volume of the whole muscles constituting the rotator cuff were quantitatively assessed using 3-dimensional 2-point Dixon magnetic resonance imaging. Ten shoulders with a partial-thickness tear, 10 shoulders with an isolated supraspinatus tear, and 10 shoulders with a massive tear involving supraspinatus and infraspinatus were compared with 10 control shoulders after matching age and sex. With segmentation of muscle boundaries, the fat fraction value and the volume of the whole rotator cuff muscles were computed. After reliabilities were determined, differences in fat fraction, muscle volume, and fat-free muscle volume were evaluated. Intra-rater and inter-rater reliabilities were regarded as excellent for fat fraction and muscle volume. Tendon rupture adversely increased the fat fraction value of the respective rotator cuff muscle (P < .002). In the massive tear group, muscle volume was significantly decreased in the infraspinatus (P = .035) and increased in the teres minor (P = .039). With subtraction of fat volume, a significant decrease of fat-free volume of the supraspinatus muscle became apparent with a massive tear (P = .003). Three-dimensional measurement could evaluate fatty infiltration and muscular volume with excellent reliabilities. The present study showed that chronic rupture of the tendon adversely increases the fat fraction of the respective muscle and indicates that the residual capacity of the rotator cuff muscles might be overestimated in patients with severe fatty infiltration. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Effect of ethanol on crystallization of the polymorphs of L-histidine

NASA Astrophysics Data System (ADS)

Wantha, Lek; Punmalee, Neeranuch; Sawaddiphol, Vanida; Flood, Adrian E.

2018-05-01

It is known that the antisolvents used for crystallization can affect the crystallization outcome and may promote the crystallization of a specific polymorph. In this study L-histidine (L-his) is used as a model substance, and ethanol was selected to be an antisolvent. The formation of the polymorphs of L-his in antisolvent crystallization as a function of supersaturation, ethanol volume fraction, and temperature was studied. The induction time for the antisolvent crystallization was also measured. The results showed that the induction time decreases with higher supersaturation and ethanol volume fraction, indicating that the nucleation rate of L-his from antisolvent crystallization (where water was used as the solvent and ethanol as the antisolvent) increases with higher supersaturation, as expected, and ethanol fraction. At all temperatures studied, the pure metastable polymorph B of L-his was obtained initially at higher ethanol volume fraction and supersaturation, while a mixture of the polymorphs A and B was obtained at lower ethanol volume fraction and supersaturation.

Tuning mechanical performance of poly(ethylene glycol) and agarose interpenetrating network hydrogels for cartilage tissue engineering.

PubMed

Rennerfeldt, Deena A; Renth, Amanda N; Talata, Zsolt; Gehrke, Stevin H; Detamore, Michael S

2013-11-01

Hydrogels are attractive for tissue engineering applications due to their incredible versatility, but they can be limited in cartilage tissue engineering applications due to inadequate mechanical performance. In an effort to address this limitation, our team previously reported the drastic improvement in the mechanical performance of interpenetrating networks (IPNs) of poly(ethylene glycol) diacrylate (PEG-DA) and agarose relative to pure PEG-DA and agarose networks. The goal of the current study was specifically to determine the relative importance of PEG-DA concentration, agarose concentration, and PEG-DA molecular weight in controlling mechanical performance, swelling characteristics, and network parameters. IPNs consistently had compressive and shear moduli greater than the additive sum of either single network when compared to pure PEG-DA gels with a similar PEG-DA content. IPNs withstood a maximum stress of up to 4.0 MPa in unconfined compression, with increased PEG-DA molecular weight being the greatest contributing factor to improved failure properties. However, aside from failure properties, PEG-DA concentration was the most influential factor for the large majority of properties. Increasing the agarose and PEG-DA concentrations as well as the PEG-DA molecular weight of agarose/PEG-DA IPNs and pure PEG-DA gels improved moduli and maximum stresses by as much as an order of magnitude or greater compared to pure PEG-DA gels in our previous studies. Although the viability of encapsulated chondrocytes was not significantly affected by IPN formulation, glycosaminoglycan (GAG) content was significantly influenced, with a 12-fold increase over a three-week period in gels with a lower PEG-DA concentration. These results suggest that mechanical performance of IPNs may be tuned with partial but not complete independence from biological performance of encapsulated cells. © 2013 Elsevier Ltd. All rights reserved.

Synthesis and characterization of mannosylated pegylated polyethylenimine as a carrier for siRNA

PubMed Central

Kim, NaJung; Jiang, Dahai; Jacobi, Ashley; Lennox, Kim A.; Rose, Scott; Behlke, Mark A.; Salem, Aliasger K.

2011-01-01

Regulation of gene expression using small interfering RNA (siRNA) is a promising strategy for research and treatment of numerous diseases. In this study, we develop and characterize a delivery system for siRNA composed of polyethylenimine (PEI), polyethylene glycol (PEG), and mannose (Man). Cationic PEI complexes and compacts siRNA, PEG forms a hydrophilic layer outside of the polyplex for steric stabilization, and mannose serves as a cell binding ligand for macrophages. The PEI-PEG-mannose delivery system was constructed in two different ways. In the first approach, mannose and PEG chains are directly conjugated to the PEI backbone. In the second approach, mannose is conjugated to one end of the PEG chain and the other end of the PEG chain is conjugated to the PEI backbone. The PEI-PEG-mannose delivery systems were synthesized with 3.45 – 13.3 PEG chains and 4.7 – 3.0 mannose molecules per PEI. The PEI-PEG-Man-siRNA polyplexes displayed a coarse surface in Scanning Electron Microscopy (SEM) images. Polyplex sizes were found to range from 169nm to 357nm. Gel retardation assays showed that the PEI-PEG-mannose polymers are able to efficiently complex with siRNA at low N/P ratios. Confocal microscope images showed that the PEI-PEG-Man-siRNA polyplexes could enter cells and localized in the lysosomes at 2 hours post-incubation. Pegylation of the PEI reduced toxicity without any adverse reduction in knockdown efficiency relative to PEI alone. Mannosylation of the PEI-PEG could be carried out without any significant reduction in knockdown efficiency relative to PEI alone. Conjugating mannose to PEI via the PEG spacer generated superior toxicity and gene knockdown activity relative to conjugating mannose and PEG directly onto the PEI backbone. PMID:21864664

Affinity partitioning of human antibodies in aqueous two-phase systems.

PubMed

Rosa, P A J; Azevedo, A M; Ferreira, I F; de Vries, J; Korporaal, R; Verhoef, H J; Visser, T J; Aires-Barros, M R

2007-08-24

The partitioning of human immunoglobulin (IgG) in a polymer-polymer and polymer-salt aqueous two-phase system (ATPS) in the presence of several functionalised polyethylene glycols (PEGs) was studied. As a first approach, the partition studies were performed with pure IgG using systems in which the target protein remained in the bottom phase when the non-functionalised systems were tested. The effect of increasing functionalised PEG concentration and the type of ligand were studied. Afterwards, selectivity studies were performed with the most successful ligands first by using systems containing pure proteins and an artificial mixture of proteins and, subsequently, with systems containing a Chinese hamster ovary (CHO) cells supernatant. The PEG/phosphate ATPS was not suitable for the affinity partitioning of IgG. In the PEG/dextran ATPS, the diglutaric acid functionalised PEGs (PEG-COOH) displayed great affinity to IgG, and all IgG could be recovered in the top phase when 20% (w/w) of PEG 150-COOH and 40% (w/w) PEG 3350-COOH were used. The selectivity of these functionalised PEGs was evaluated using an artificial mixture of proteins, and PEG 3350-COOH did not show affinity to IgG in the presence of typical serum proteins such as human serum albumin and myoglobin, while in systems with PEG 150-COOH, IgG could be recovered with a yield of 91%. The best purification of IgG from the CHO cells supernatant was then achieved in a PEG/dextran ATPS in the presence of PEG 150-COOH with a recovery yield of 93%, a purification factor of 1.9 and a selectivity to IgG of 11. When this functionalised PEG was added to the ATPS, a 60-fold increase in selectivity was observed when compared to the non-functionalised systems.

SU-E-T-480: Radiobiological Dose Comparison of Single Fraction SRS, Multi-Fraction SRT and Multi-Stage SRS of Large Target Volumes Using the Linear-Quadratic Formula

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, C; Hrycushko, B; Jiang, S

2014-06-01

Purpose: To compare the radiobiological effect on large tumors and surrounding normal tissues from single fraction SRS, multi-fractionated SRT, and multi-staged SRS treatment. Methods: An anthropomorphic head phantom with a centrally located large volume target (18.2 cm{sup 3}) was scanned using a 16 slice large bore CT simulator. Scans were imported to the Multiplan treatment planning system where a total prescription dose of 20Gy was used for a single, three staged and three fractionated treatment. Cyber Knife treatment plans were inversely optimized for the target volume to achieve at least 95% coverage of the prescription dose. For the multistage plan,more » the target was segmented into three subtargets having similar volume and shape. Staged plans for individual subtargets were generated based on a planning technique where the beam MUs of the original plan on the total target volume are changed by weighting the MUs based on projected beam lengths within each subtarget. Dose matrices for each plan were export in DICOM format and used to calculate equivalent dose distributions in 2Gy fractions using an alpha beta ratio of 10 for the target and 3 for normal tissue. Results: Singe fraction SRS, multi-stage plan and multi-fractionated SRT plans had an average 2Gy dose equivalent to the target of 62.89Gy, 37.91Gy and 33.68Gy, respectively. The normal tissue within 12Gy physical dose region had an average 2Gy dose equivalent of 29.55Gy, 16.08Gy and 13.93Gy, respectively. Conclusion: The single fraction SRS plan had the largest predicted biological effect for the target and the surrounding normal tissue. The multi-stage treatment provided for a more potent biologically effect on target compared to the multi-fraction SRT treatments with less biological normal tissue than single-fraction SRS treatment.« less

Microencapsulation of islets within alginate/poly(ethylene glycol) gels cross-linked via Staudinger ligation

PubMed Central

Hall, Kristina K.; Gattás-Asfura, Kerim M.; Stabler, Cherie L.

2010-01-01

Functionalized alginate and PEG polymers were used to generate covalently linked alginate-PEG (XAlgPEG) microbeads of high stability. The cell-compatible Staudinger ligation scheme was used to chemoselectively cross-link phosphine-terminated poly(ethylene glycol) (PEG) to azide-functionalized alginate, resulting in XAlgPEG hydrogels. XAlgPEG microbeads were formed by co-incubation of the two polymers, followed by ionic cross-linking of the alginate using barium ions. The enhanced stability and gel properties of the resulting XAlgPEG microbeads, as well as the compatibility of these polymers for the encapsulation of islets and beta cells lines, were investigated. Our data show that XAlgPEG microbeads exhibit superior resistance to osmotic swelling compared to traditional barium cross-linked alginate (Ba-Alg) beads, with a 5-fold reduction in observed swelling, as well as resistance to dissolution via chelation solution. Diffusion and porosity studies found XAlgPEG beads to exhibit properties comparable to standard Ba-Alg. Our data found XAlgPEG microbeads to be highly cell compatible with insulinoma cell lines, as well as rat and human pancreatic islets, where the viability and functional assessment of cells within XAlgPEG were comparable to Ba-Alg controls. The remarkable improved stability, as well as demonstrated cellular compatibility, of XAlgPEG hydrogels makes them an appealing option for a wide variety of tissue engineering applications. PMID:20654745

Polyethylene glycol as marker for nitrofurazone allergy: 20 years of experience from Turkey.

PubMed

Özkaya, Esen; Kılıç, Sıla

2018-03-01

Polyethylene glycols (PEGs) and propylene glycol (PG) are used as vehicles in various medicinal and cosmetic products. They are potential contact sensitizers, including low molecular weight PEGs in nitrofurazone preparations that are still widely used in Turkey. To investigate the prevalence of allergic contact dermatitis caused by PEG and PG in a relatively large group of patients in Turkey. In this retrospective, cross-sectional, single-centre study, 836 patients patch tested with PEG and PG between 1996 and 2015 were reviewed. Thirty-five patients (4.2%) showed positive patch test reactions to PEG, and 7 (0.8%) showed positive patch test reactions to PG, partly as late positive reactions with PEG. PEG sensitivity was almost exclusively related to nitrofurazone allergy. Patch test reactions to PG were currently relevant mainly with regard to the use of minoxidil, and antiherpetic or corticosteroid creams. Ten patients (25%) had concomitant contact allergies to various topical drugs containing mainly PEGs. PEG sensitivity seems to be a marker for contact allergy to topical nitrofurazone in Turkey. Nitrofurazone allergy appears to favour concomitant sensitization to PEG. We would suggest the inclusion of PEG in an extended baseline patch test series in Turkey. Late patch test readings are important to diagnose delayed positive reactions to PEG. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparison of Polyethylene Glycol-Electrolyte Solution vs Polyethylene Glycol-3350 for the Treatment of Fecal Impaction in Pediatric Patients

PubMed Central

Boles, Erin E.; Gaines, Cameryn L.

2015-01-01

OBJECTIVES: The objective of this study was to evaluate the safety and efficacy of polyethylene glycol-electrolyte solution vs polyethylene glycol-3350 for the treatment of fecal impaction in pediatric patients. METHODS: A retrospective, observational, institutional review board–approved study was conducted over a 1-year time period. Patients were included in the study if they were admitted to the hospital with a diagnosis of fecal impaction or constipation and were treated with either polyethylene glycol-electrolyte solution (PEG-ES) or polyethylene glycol-3350 (PEG-3350). Patients were excluded if they were discharged prior to resolution of treatment and/or did not receive PEG-ES or PEG-3350. RESULTS: Fifty-one patients (ranging in age from 1 month to 15 years) were evaluated: 23 patients received PEG-ES and 28 patients received PEG-3350. Sex, race, age, and weight were not statistically different between the 2 groups. Resolution of fecal impaction was not significantly different between PEG-ES vs PEG-3350 (87% and 86%, respectively; p = 0.87). There was only 1 reported side effect with PEG-3350, vs 11 reported side effects with PEG-ES (p < 0.01). CONCLUSIONS: Theses results suggest that PEG-3350 is as effective as PEG-ES for the treatment of fecal impaction in pediatric patients and is associated with fewer side effects. PMID:26170773

Comparison of Polyethylene Glycol-Electrolyte Solution vs Polyethylene Glycol-3350 for the Treatment of Fecal Impaction in Pediatric Patients.

PubMed

Boles, Erin E; Gaines, Cameryn L; Tillman, Emma M

2015-01-01

The objective of this study was to evaluate the safety and efficacy of polyethylene glycol-electrolyte solution vs polyethylene glycol-3350 for the treatment of fecal impaction in pediatric patients. A retrospective, observational, institutional review board-approved study was conducted over a 1-year time period. Patients were included in the study if they were admitted to the hospital with a diagnosis of fecal impaction or constipation and were treated with either polyethylene glycol-electrolyte solution (PEG-ES) or polyethylene glycol-3350 (PEG-3350). Patients were excluded if they were discharged prior to resolution of treatment and/or did not receive PEG-ES or PEG-3350. Fifty-one patients (ranging in age from 1 month to 15 years) were evaluated: 23 patients received PEG-ES and 28 patients received PEG-3350. Sex, race, age, and weight were not statistically different between the 2 groups. Resolution of fecal impaction was not significantly different between PEG-ES vs PEG-3350 (87% and 86%, respectively; p = 0.87). There was only 1 reported side effect with PEG-3350, vs 11 reported side effects with PEG-ES (p < 0.01). Theses results suggest that PEG-3350 is as effective as PEG-ES for the treatment of fecal impaction in pediatric patients and is associated with fewer side effects.

Effect on the operation properties of DMBR with the addition of GAC

NASA Astrophysics Data System (ADS)

Lin, Jizhi; Zhang, Qian; Hong, Junming

2017-01-01

The membrane bioreactor and dynamic membrane bioreactor were used to examine the effect of granular activated carbon (GAC) on the treatment of synthetic wastewater. After the addition of different volume fractions GAC in the DMBR, the operation parameters, effluent COD, NH4 +-N, NO3 --N, TN concentrations and sludge viscosity of the bioreactor was investigated. The results showed that the addition of GAC could relieve the membrane fouling and improve the removal efficiencies of pollutants in the DMBR. The effluent concentrations of pollutants were linear correlation with the addition of volume fractions of GAC in the bioreactor. The value of R2 of each modulation was almost more than 0.9. The sludge viscosity was almost not affected by the volume fractions of GAC in the bioreactor. The best volume fractions of GAC were 20% in the DMBR.

Tissue microstructure features derived from anomalous diffusion measurements in magnetic resonance imaging.

PubMed

Yu, Qiang; Reutens, David; O'Brien, Kieran; Vegh, Viktor

2017-02-01

Tissue microstructure features, namely axon radius and volume fraction, provide important information on the function of white matter pathways. These parameters vary on the scale much smaller than imaging voxels (microscale) yet influence the magnetic resonance imaging diffusion signal at the image voxel scale (macroscale) in an anomalous manner. Researchers have already mapped anomalous diffusion parameters from magnetic resonance imaging data, but macroscopic variations have not been related to microscale influences. With the aid of a tissue model, we aimed to connect anomalous diffusion parameters to axon radius and volume fraction using diffusion-weighted magnetic resonance imaging measurements. An ex vivo human brain experiment was performed to directly validate axon radius and volume fraction measurements in the human brain. These findings were validated using electron microscopy. Additionally, we performed an in vivo study on nine healthy participants to map axon radius and volume fraction along different regions of the corpus callosum projecting into various cortical areas identified using tractography. We found a clear relationship between anomalous diffusion parameters and axon radius and volume fraction. We were also able to map accurately the trend in axon radius along the corpus callosum, and in vivo findings resembled the low-high-low-high behaviour in axon radius demonstrated previously. Axon radius and volume fraction measurements can potentially be used in brain connectivity studies and to understand the implications of white matter structure in brain diseases and disorders. Hum Brain Mapp 38:1068-1081, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Raman scattering studies on PEG functionalized hydroxyapatite nanoparticles.

PubMed

Yamini, D; Devanand Venkatasubbu, G; Kumar, J; Ramakrishnan, V

2014-01-03

The pure hydroxyapatite (HAP) nanoparticles (NPs) have been synthesized by wet chemical precipitation method. Raman spectral measurements have been made for pure HAP, pure Polyethylene glycol (PEG) 6000 and PEG coated HAP in different mass ratios (sample 1, sample 2 and sample 3). The peaks observed in Raman spectrum of pure HAP and the XRD pattern have confirmed the formation of HAP NPs. Vibrational modes have been assigned for pure HAP and pure PEG 6000. The observed variation in peak position of Raman active vibrational modes of PEG in PEG coated HAP has been elucidated in this work, in terms of intermolecular interactions between PEG and HAP. Further these results suggest that the functionalization of nanoparticles may be independent of PEG mass. Copyright © 2013 Elsevier B.V. All rights reserved.

Combined therapy with danazol, pegilated interferon, and ribavirin improves thrombocytopenia and liver injury in rats with fibrosis.

PubMed

Alvarez, Guillermo Cabrera; Madrid-Marina, Vicente; Jimenez-Mendez, Ricardo; Buitimea, Angel Leon; Román, Margarita Bahena; Cortez-Gomez, Rudyard; Esparza, Jorge Reyes; Rodríguez-Fragoso, Lourdes

2007-01-01

The aim of this study was to investigate the effects of combinations of pegilated-interferon (PEG-IFN), ribavirin, and danazol on thrombocytopenia and liver injury in rats with fibrosis. Male adult Wistar rats were treated with either mineral oil, danazol (0.83 mg/kg per day), PEG-interferon alpha-2a (PEG-IFN, 0.3 microg/ week) + ribavirin (12 mg/kg per day), PEG-IFN + ribavirin + danazol, CCl(4) (4 g/kg for eight weeks), CCl(4) + PEG-IFN + ribavirin, or CCl(4) + PEG-IFN + ribavirin+ danazol. The following assays were conducted: hematology, clinical chemistry, liver function, liver fibrosis, lymphocyte cytokine mRNA expression, and bone-marrow DNA content. Platelet counts were low in sham-treated animals and animals treated with PEG- IFN + ribavirin (30% and 25% respectively; P < 0.05). PEG-IFN + ribavirin + danazol reduced platelet counts of fibrotic animals by only 9% (P < 0.05). PEG- IFN + ribavirin reduced hepatic collagen content by 50%, whereas danazol + PEG-IFN + ribavirin reduced hepatic collagen content by 60% (P < 0.05). PEG-IFN + ribavirin reduced the total bilirubin concentration by 27%, alanine amino transferase (ALT) activity by 75% and gamma-glutamyl transpeptidase (gamma-GTP) activity by 74% (P < 0.05). In contrast, danazol + PEG-IFN + ribavirin reduced total bilirubin levels by 61%, alkaline phosphatase activity by 45%, ALT activity by 76%, and gamma-GTP activity by 74% (P < 0.05). The only treatment that increased interleukin 10 (IL-10) mRNA in fibrotic rats was PEG-IFN + ribavirin. However, danazol + PEG-IFN + ribavirin reduced the expression of IL-6, IL-10, tumor necrosis factor alpha and transforming growth factor ss. Bone-marrow DNA content was not altered by any treatment. In conclusion, PEG-IFN + ribavirin + danazol could be a new therapeutic option for patients with liver injury, fibrosis, and thrombocytopenia.

Current status of percutaneous endoscopic gastrostomy (PEG) in a general hospital in Japan: a cross-sectional study

PubMed Central

Kusano, Chika; Yamada, Nobuo; Kikuchi, Kenji; Hashimoto, Masaji; Gotoda, Takuji

2016-01-01

Background: There has been debate over the indications for percutaneous endoscopic gastrostomy (PEG) in recent years in Japan. In addition, the level of satisfaction of patients and patient’s family after PEG remains unclear. The aim of this study was to investigate the current status of PEG and the level of satisfaction of patients and patients’ families after PEG in Japan. Methods: We reviewed the existing data of all patients who underwent PEG tube insertion at Yuri Kumiai General Hospital (Akita, Japan) between February 2000 and December 2010. We examined the following points: underlying diseases requiring PEG, levels of consciousness, and performance status. We also sent a questionnaire to the patients and patient’s families to ask about their satisfaction with and thoughts about PEG. Results: The data of 545 patients who underwent PEG were reviewed. There were 295 men and 250 women, with a mean age of 77.2 ± 11.4 years. PEG was indicated most frequently for cerebrovascular disorders (48.2%, 239/545). There were 515 (94.4%, 515/545) patients showing consciousness disturbance and 444 (81.5%, 444/545) bedridden patients. The questionnaire was answered by one patient himself and 316 patients’ families. When asked, “Was performing PEG a good decision?”, 57.5% (182/316) of the patients’ families answered yes. Meanwhile, when patients’ family members were asked if they would wish to undergo PEG if they were in the same condition as the patient, 28.4% (90/316) answered yes, whereas 55.3% (175/316) answered no. Conclusions: Few patients were able to make their own decision about PEG tube placement because of consciousness disturbance. As a result, many family members of the patients did not want to experience PEG for themselves. Future studies should be performed to clarify the quality of life and ethical aspects associated with PEG. PMID:27313796

The effect of bi-terminal PEGylation of an integrin  α vβ 6-targeted 18F peptide on pharmacokinetics and tumor uptake

DOE PAGES

Hausner, Sven H.; Bauer, Nadine; Hu, Lina Y.; ...

2015-03-26

Radiotracers based on the peptide A20FMDV2 selectively target the cell surface receptor integrin α vβ 6. This integrin has been identified as a prognostic indicator correlating with the severity of disease for several challenging malignancies. In previous studies of A20FMDV2 peptides labeled with 4- 18F-fluorobenzoic acid ( 18F-FBA), we have shown that the introduction of poly(ethylene glycol) (PEG) improves pharmacokinetics, including increased uptake in α vβ 6-expressing tumors. The present study evaluated the effect of site-specific C-terminal or dual (N- and C-terminal) PEGylation, yielding 18F-FBA-A20FMDV2-PEG 28 (4) and 18F-FBA-PEG 28-A20FMDV2-PEG 28 (5), on α vβ 6-targeted tumor uptake and pharmacokinetics.more » The results are compared with 18F-FBA–labeled A20FMDV2 radiotracers (1–3) bearing either no PEG or different PEG units at the N terminus. The radiotracers were prepared and radiolabeled on solid phase. Using 3 cell lines, DX3puroβ6 (α vβ 6+), DX3puro (α vβ 6–), and BxPC-3 (α vβ 6+), we evaluated the radiotracers in vitro (serum stability; cell binding and internalization) and in vivo in mouse models bearing paired DX3puroβ6–DX3puro and, for 5, BxPC-3 xenografts. Here, the size and location of the PEG units significantly affected α vβ 6 targeting and pharmacokinetics. Although the C-terminally PEGylated 4 showed some improvements over the un-PEGylated 18F-FBA-A20FMDV2 (1), it was the bi-terminally PEGylated 5 that displayed the more favorable combination of high α vβ 6 affinity, selectivity, and pharmacokinetic profile. In vitro, 5 bound to α vβ 6-expressing DX3puroβ6 and BxPC-3 cells with 60.5% ± 3.3% and 48.8% ± 8.3%, respectively, with a significant fraction of internalization (37.2% ± 4.0% and 37.6% ± 4.1% of total radioactivity, respectively). By comparison, in the DX3puro control 5 showed only 3.0% ± 0.5% binding and 0.9% ± 0.2% internalization. In vivo, 5 maintained high, α vβ 6-directed binding in the paired DX3puroβ6–DX3puro model (1 h: DX3puroβ6, 2.3 ± 0.2 percentage injected dose per gram [%ID/g]; DX3puroβ6/DX3puro ratio, 6.5:1; 4 h: 10.7:1). In the pancreatic BxPC-3 model, uptake was 4.7 ± 0.9 %ID/g (1 h) despite small tumor sizes (20–80 mg). In conclusion, the bi-PEGylated radiotracer 5 showed a greatly improved pharmacokinetic profile, beyond what was predicted from individual N- or C-terminal PEGylation. It appears that the 2 PEG units acted synergistically to result in an improved metabolic profile including high α vβ 6+ tumor uptake and retention.« less

The effect of bi-terminal PEGylation of an integrin  α vβ 6-targeted 18F peptide on pharmacokinetics and tumor uptake

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hausner, Sven H.; Bauer, Nadine; Hu, Lina Y.

Radiotracers based on the peptide A20FMDV2 selectively target the cell surface receptor integrin α vβ 6. This integrin has been identified as a prognostic indicator correlating with the severity of disease for several challenging malignancies. In previous studies of A20FMDV2 peptides labeled with 4- 18F-fluorobenzoic acid ( 18F-FBA), we have shown that the introduction of poly(ethylene glycol) (PEG) improves pharmacokinetics, including increased uptake in α vβ 6-expressing tumors. The present study evaluated the effect of site-specific C-terminal or dual (N- and C-terminal) PEGylation, yielding 18F-FBA-A20FMDV2-PEG 28 (4) and 18F-FBA-PEG 28-A20FMDV2-PEG 28 (5), on α vβ 6-targeted tumor uptake and pharmacokinetics.more » The results are compared with 18F-FBA–labeled A20FMDV2 radiotracers (1–3) bearing either no PEG or different PEG units at the N terminus. The radiotracers were prepared and radiolabeled on solid phase. Using 3 cell lines, DX3puroβ6 (α vβ 6+), DX3puro (α vβ 6–), and BxPC-3 (α vβ 6+), we evaluated the radiotracers in vitro (serum stability; cell binding and internalization) and in vivo in mouse models bearing paired DX3puroβ6–DX3puro and, for 5, BxPC-3 xenografts. Here, the size and location of the PEG units significantly affected α vβ 6 targeting and pharmacokinetics. Although the C-terminally PEGylated 4 showed some improvements over the un-PEGylated 18F-FBA-A20FMDV2 (1), it was the bi-terminally PEGylated 5 that displayed the more favorable combination of high α vβ 6 affinity, selectivity, and pharmacokinetic profile. In vitro, 5 bound to α vβ 6-expressing DX3puroβ6 and BxPC-3 cells with 60.5% ± 3.3% and 48.8% ± 8.3%, respectively, with a significant fraction of internalization (37.2% ± 4.0% and 37.6% ± 4.1% of total radioactivity, respectively). By comparison, in the DX3puro control 5 showed only 3.0% ± 0.5% binding and 0.9% ± 0.2% internalization. In vivo, 5 maintained high, α vβ 6-directed binding in the paired DX3puroβ6–DX3puro model (1 h: DX3puroβ6, 2.3 ± 0.2 percentage injected dose per gram [%ID/g]; DX3puroβ6/DX3puro ratio, 6.5:1; 4 h: 10.7:1). In the pancreatic BxPC-3 model, uptake was 4.7 ± 0.9 %ID/g (1 h) despite small tumor sizes (20–80 mg). In conclusion, the bi-PEGylated radiotracer 5 showed a greatly improved pharmacokinetic profile, beyond what was predicted from individual N- or C-terminal PEGylation. It appears that the 2 PEG units acted synergistically to result in an improved metabolic profile including high α vβ 6+ tumor uptake and retention.« less

Turbulent forced convection of nanofluids downstream an abrupt expansion

NASA Astrophysics Data System (ADS)

Kimouche, Abdelali; Mataoui, Amina

2018-03-01

Turbulent forced convection of Nanofluids through an axisymmetric abrupt expansion is investigated numerically in the present study. The governing equations are solved by ANYS 14.0 CFD code based on the finite volume method by implementing the thermo-physical properties of each nanofluid. All results are analyzed through the evolutions of skin friction coefficient and Nusselt number. For each nanofluid, the effect of both volume fraction and Reynolds number on this type of flow configuration, are examined. An increase on average Nusselt number with the volume fraction and Reynolds number, are highlighted and correlated. Two relationships are proposed. The first one, determines the average Nusselt number versus Reynolds number, volume fraction and the ratio of densities of the solid particles to that of the base fluid ( \\overline{Nu}=f(\\operatorname{Re},φ, ρ_s/ρ_f) ). The second one varies according Reynolds number, volume fraction and the conductivities ratio of solid particle to that of the base fluid ( \\overline{Nu}=f(\\operatorname{Re},φ, k_s/k_f) ).

SU-E-T-429: Uncertainties of Cell Surviving Fractions Derived From Tumor-Volume Variation Curves

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chvetsov, A

2014-06-01

Purpose: To evaluate uncertainties of cell surviving fraction reconstructed from tumor-volume variation curves during radiation therapy using sensitivity analysis based on linear perturbation theory. Methods: The time dependent tumor-volume functions V(t) have been calculated using a twolevel cell population model which is based on the separation of entire tumor cell population in two subpopulations: oxygenated viable and lethally damaged cells. The sensitivity function is defined as S(t)=[δV(t)/V(t)]/[δx/x] where δV(t)/V(t) is the time dependent relative variation of the volume V(t) and δx/x is the relative variation of the radiobiological parameter x. The sensitivity analysis was performed using direct perturbation method wheremore » the radiobiological parameter x was changed by a certain error and the tumor-volume was recalculated to evaluate the corresponding tumor-volume variation. Tumor volume variation curves and sensitivity functions have been computed for different values of cell surviving fractions from the practically important interval S{sub 2}=0.1-0.7 using the two-level cell population model. Results: The sensitivity functions of tumor-volume to cell surviving fractions achieved a relatively large value of 2.7 for S{sub 2}=0.7 and then approached zero as S{sub 2} is approaching zero Assuming a systematic error of 3-4% we obtain that the relative error in S{sub 2} is less that 20% in the range S2=0.4-0.7. This Resultis important because the large values of S{sub 2} are associated with poor treatment outcome should be measured with relatively small uncertainties. For the very small values of S2<0.3, the relative error can be larger than 20%; however, the absolute error does not increase significantly. Conclusion: Tumor-volume curves measured during radiotherapy can be used for evaluation of cell surviving fractions usually observed in radiation therapy with conventional fractionation.« less

Steric and electrostatic surface forces on sulfonated PEG graft surfaces with selective albumin adsorption.

PubMed

Bremmell, Kristen E; Britcher, Leanne; Griesser, Hans J

2013-06-01

Addition of ionized terminal groups to PEG graft layers may cause additional interfacial forces to modulate the net interfacial interactions between PEG graft layers and proteins. In this study we investigated the effect of terminal sulfonate groups, characterizing PEG-aldehyde (PEG-CHO) and sulfonated PEG (PEG-SO3) graft layers by XPS and colloid probe AFM interaction force measurements as a function of ionic strength, in order to determine surface forces relevant to protein resistance and models of bio-interfacial interaction of such graft coatings. On the PEG-CHO surface the measured interaction force does not alter with ionic strength, typical of a repulsive steric barrier coating. An analogous repulsive interaction force of steric origin was also observed on the PEG-SO3 graft coating; however, the net interaction force changed with ionic strength. Interaction forces were modelled by steric and electrical double layer interaction theories, with fitting to a scaling theory model enabling determination of the spacing and stretching of the grafted chains. Albumin, fibrinogen, and lysozyme did not adsorb on the PEG-CHO coating, whereas the PEG graft with terminal sulfonate groups showed substantial adsorption of albumin but not fibrinogen or lysozyme from 0.15 M salt solutions. Under lower ionic strength conditions albumin adsorption was again minimized as a result of the increased electrical double-layer interaction observed with the PEG-SO3 modified surface. This unique and unexpected adsorption behaviour of albumin provides an alternative explanation to the "negative cilia" model used by others to rationalize observed thromboresistance on PEG-sulfonate coatings. Copyright © 2013 Elsevier B.V. All rights reserved.

Quantitative analysis of polyethylene glycol (PEG) and PEGylated proteins in animal tissues by LC-MS/MS coupled with in-source CID.

PubMed

Gong, Jiachang; Gu, Xiaomei; Achanzar, William E; Chadwick, Kristina D; Gan, Jinping; Brock, Barry J; Kishnani, Narendra S; Humphreys, W Griff; Iyer, Ramaswamy A

2014-08-05

The covalent conjugation of polyethylene glycol (PEG, typical MW > 10k) to therapeutic peptides and proteins is a well-established approach to improve their pharmacokinetic properties and diminish the potential for immunogenicity. Even though PEG is generally considered biologically inert and safe in animals and humans, the slow clearance of large PEGs raises concerns about potential adverse effects resulting from PEG accumulation in tissues following chronic administration, particularly in the central nervous system. The key information relevant to the issue is the disposition and fate of the PEG moiety after repeated dosing with PEGylated proteins. Here, we report a novel quantitative method utilizing LC-MS/MS coupled with in-source CID that is highly selective and sensitive to PEG-related materials. Both (40K)PEG and a tool PEGylated protein (ATI-1072) underwent dissociation in the ionization source of mass spectrometer to generate a series of PEG-specific ions, which were subjected to further dissociation through conventional CID. To demonstrate the potential application of the method to assess PEG biodistribution following PEGylated protein administration, a single dose study of ATI-1072 was conducted in rats. Plasma and various tissues were collected, and the concentrations of both (40K)PEG and ATI-1072 were determined using the LC-MS/MS method. The presence of (40k)PEG in plasma and tissue homogenates suggests the degradation of PEGylated proteins after dose administration to rats, given that free PEG was absent in the dosing solution. The method enables further studies for a thorough characterization of disposition and fate of PEGylated proteins.

Physicochemical and in vitro deposition properties of salbutamol sulphate/ipratropium bromide and salbutamol sulphate/excipient spray dried mixtures for use in dry powder inhalers.

PubMed

Corrigan, Deirdre O; Corrigan, Owen I; Healy, Anne Marie

2006-09-28

The physicochemical and aerodynamic properties of spray dried powders of the drug/drug mixture salbutamol sulphate/ipratropium bromide were investigated. The in vitro deposition properties of spray dried salbutamol sulphate and the spray dried drug/excipient mixtures salbutamol sulphate/lactose and salbutamol sulphate/PEG were also determined. Spray drying ipratropium bromide monohydrate resulted in a crystalline material from both aqueous and ethanolic solution. The product spray dried from aqueous solution consisted mainly of ipratropium bromide anhydrous. There was evidence of the presence of another polymorphic form of ipratropium bromide. When spray dried from ethanolic solution the physicochemical characterisation suggested the presence of an ipratropium bromide solvate with some anhydrous ipratropium bromide. Co-spray drying salbutamol sulphate with ipratropium bromide resulted in amorphous composites, regardless of solvent used. Particles were spherical and of a size suitable for inhalation. Twin impinger studies showed an increase in the fine particle fraction (FPF) of spray dried salbutamol sulphate compared to micronised salbutamol sulphate. Co-spray dried salbutamol sulphate:ipratropium bromide 10:1 and 5:1 systems also showed an increase in FPF compared to micronised salbutamol sulphate. Most co-spray dried salbutamol sulphate/excipient systems investigated demonstrated FPFs greater than that of micronised drug alone. The exceptions to this were systems containing PEG 4000 20% or PEG 20,000 40% both of which had FPFs not significantly different from micronised salbutamol sulphate. These two systems were crystalline unlike most of the other spray dried composites examined which were amorphous in nature.

Collagenase-labile polyurethane urea synthesis and processing into hollow fiber membranes.

PubMed

Fu, Hui-Li; Hong, Yi; Little, Steven R; Wagner, William R

2014-08-11

As a means to stimulate wound healing, a hollow fiber membrane system might be placed within a wound bed to provide local and externally regulated controlled delivery of regenerative factors. After sufficient healing, it would be desirable to triggerably degrade these fibers as opposed to pulling them out. Accordingly, a series of enzymatically degradable thermoplastic elastomers was developed as potential hollow fiber base material. Polyurethane ureas (PUUs) were synthesized based on 1, 4-diisocyanatobutane, polycaprolactone (PCL) diol and polyethylene glycol (PEG) at different molar fractions as soft segments, and collagenase-sensitive peptide GGGLGPAGGK-NH2 as a chain extender (defined as PUU-CLxEGy-peptide, where x and y are the respective molar percents). In these polymers, PEG in the polymer backbone decreased tensile strengths and initial moduli of solvent-cast films in the wet state, while increasing water absorption. Collagenase degradation was observed at 75% relative PEG content in the soft segment. Control PUUs with putrescine or nonsense peptide chain extenders did not degrade acutely in collagenase. Conduits electrospun from PUU-CL25EG75-peptide and PUU-CL50EG50-peptide exhibited appropriate mechanical strength and sustained release of a model protein from the tube lumen for 7 days. Collapse of PUU-CL25EG75-peptide tubes occurred after collagenase degradation for 3 days. In conclusion, through molecular design, synthesis and characterization, a collagenase-labile PUU-CL25EG75-peptide polymer was identified that exhibited the desired traits of triggerable lability, processability, and the capacity to act as a membrane to facilitate controlled protein release.

Preparation and evaluation of a new releasable PEGylated tumor necrosis factor-α (TNF-α) conjugate for therapeutic application.

PubMed

Dai, ChuanYun; Fu, Ya; Chen, ShaoCheng; Li, Biao; Yao, Bo; Liu, WanHong; Zhu, LiQing; Chen, Nan; Chen, Ji; Zhang, Qiang

2013-01-01

To design a releasable PEGylated TNF-α (rPEG-TNF-α), a cathepsin B-sensitive dipeptide (Val-Cit moiety) was inserted into conventional PEG-modified TNF-α (PEG-TNF-α), facilitating its clinical use for anti-tumor therapy. Comparative pharmacokinetic and pharmacodynamic studies showed that the half-lives of both PEGylated forms of TNF-α were ∼60-fold greater than that of unmodified TNF-α. In addition, the in vitro bioactivity of rPEG-TNF-α was greater than that of PEG-TNF-α with the same degree of PEG modification. Release of TNF-α from rPEG-TNF-α in vitro was dependent on the presence of cathepsin B and was inhibited by a cathepsin B inhibitor. Despite the potent cytotoxicity of unmodified TNF-α against normal cells, its PEGylated forms at higher TNF-α concentrations showed low cytotoxic activity against these cells. In contrast, both forms of PEGylated TNF-α showed potent cytotoxic activity against the B16 and L929 cell lines, with rPEG-TNF-α being 5- and 9-fold more potent, respectively, than PEG-TNF-α. Moreover, rPEG-TNF-α was a more potent in vivo antitumor agent than PEG-TNF-α.

The effects of oil-in-water nanoemulsion polyethylene glycol surface density on intracellular stability, pharmacokinetics, and biodistribution in tumor bearing mice.

PubMed

Hak, Sjoerd; Garaiova, Zuzana; Olsen, Linda Therese; Nilsen, Asbjørn Magne; de Lange Davies, Catharina

2015-04-01

Lipid-based nanoparticles are extensively studied for drug delivery. These nanoparticles are often surface-coated with polyethylene glycol (PEG) to improve their biodistribution. Until now, the effects of varying PEG surface density have been studied in a narrow and low range. Here, the effects of high and a broad range of PEG surface densities on the in vivo performance of lipid-based nanoparticles were studied. Oil-in-water nanoemulsions were prepared with PEG surface densities of 5-50 mol%. Confocal microscopy was used to assess intracellular disintegration in vitro. In vivo pharmacokinetics and biodistribution in tumor bearing mice were studied using a small animal optical imager. PEG surface density did not affect intracellular nanoemulsion stability. Surprisingly, circulation half-lives decreased with increasing PEG surface density. A plausible explanation was that nanoemulsion with high (50 mol%) PEG surface density activated the complement in a whole blood assay, whereas nanoemulsion with low (5 mol%) PEG density did not. In vivo, nanoemulsion with low PEG surface density was mostly confined to the tumor and organs of the mononuclear phagocyte system, whereas nanoemulsion with high PEG density accumulated throughout the mouse. Optimal PEG surface density of lipid-based nanoparticles for tumor targeting was found to be below 10 mol%.

Planar measurements of soot volume fraction and OH in a JP-8 pool fire

DOE Office of Scientific and Technical Information (OSTI.GOV)

Henriksen, Tara L.; Ring, Terry A.; Eddings, Eric G.

2009-07-15

The simultaneous measurement of soot volume fraction by laser induced incandescence (LII) and qualitative imaging of OH by laser induced fluorescence (LIF) was performed in a JP-8 pool fire contained in a 152 mm diameter pan. Line of sight extinction was used to calibrate the LII system in a laminar flame, and to provide an independent method of measuring average soot volume fraction in the turbulent flame. The presence of soot in the turbulent flame was found to be approximately 50% probable, resulting in high levels of optical extinction, which increased slightly through the flame from approximately 30% near themore » base, to approximately 50% at the tip. This high soot loading pushes both techniques toward their detection limit. Nevertheless, useful accuracy was obtained, with the LII measurement of apparent extinction in the turbulent flame being approximately 21% lower than a direct measurement, consistent with the influence of signal trapping. The axial and radial distributions of soot volume fraction are presented, along with PDFs of volume fraction, and new insight into the behavior of soot sheets in pool fires are sought from the simultaneous measurements of OH and LII. (author)« less

INFLUENCE OF LIPOPHILIC AND HYDROPHILIC CO-MONOMERS ON THE HYDRODYNAMIC DIAMETER OF THERMOSENSITIVE NIPA DERIVATIVES FOR THERMALLY CONTROLLED DRUG DELIVERY.

PubMed

Musial, Witold; Gasztych, Monika; Kokol, Vanja; Mucha, Igor; Makanis, Aleksandra; Kolodziejczyk, Woiciech; Gola, Agnieszka

2017-01-01

For modem drug delivery, new drug carriers sensitive to various factors and with size in the range of micro- and nanometers are required. The aim of this work was to evaluate the influence of hydrophilic and hydrophobic co-monomers on the hydrodynamic diameter of three co-polymers of N-isopropylacrylamide (NIPA) nanogels synthesized at 70*C in the presence of potassium persulfate (KPS) as the initiator and N.N'-methylene bis-acrylamide (MBA) as the cross-linker. The first batch of nanoparticles was synthesized without co-monomer, whereas poly(ethylene glycol) methyl ether acrylate (PEG-MEA), and N-teii-butylacrylamide (NTB), were implemented as co-monomers for the second and third batch. Hydrodynamic diameter of nanoparticles was in the range 550-800 rn. The compositions of the synthesized co-polymer nanoparticles were con- firmed via IR and NMR analyses. The SFPP conditions resulted in hydrodynamic diameters ranging from approximately 550 to 800 nm at temperatures lower than the volume phase transition temperature (VPTT) and diameters ranging from 250 to 600 nm at temperatures above the VPTT, where the VPTT was between 26 and 41'C. The polydispersity index (PDI) showed a maximum or a minimum value at the VPTT, which was an important indicator of the volume phase transition. According to the PDI observation during thermal cycling, the addition of NTB into the polymeric chain resulted in maximal values of the PDI at the VPIT, similar to the case of nanoparticles without any additional co-monomers. In contrast, in the case of PEG-MEA, the PDI presented a minimal value. Dynamic light scattering (DLS) volume measurements, performed simultaneously with spectral methods, may lead to a fast evaluation of nanoparticles prepared by SFPP.

Predicting Rectal and Bladder Overdose During the Course of Prostate Radiotherapy Using Dose-Volume Data From Initial Treatment Fractions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murthy, Vedang, E-mail: vmurthy@actrec.gov.in; Shukla, Pragya; Adurkar, Pranjal

2012-09-01

Purpose: To evaluate whether information from the initial fractions can determine which patients are likely to consistently exceed their planning dose-volume constraints during the course of radiotherapy for prostate cancer. Methods and Materials: Ten patients with high-risk prostate cancer were treated with helical tomotherapy to a dose of 60 Gy in 20 fractions. The prostate, rectum, and bladder were recontoured on their daily megavoltage computed tomography scans and the dose was recalculated. The bladder and rectal volumes (in mL) receiving {>=}100% and {>=}70% of the prescribed dose in each fraction and in the original plans were recorded. A fraction formore » which the difference between planned and delivered was more than 2 mL was considered a volume failure. Similarly if the difference in the planned and delivered maximum dose (D{sub max}) was {>=}1% for the rectum and bladder, the fraction was considered a dose failure. Each patient's first 3 to 5 fractions were analyzed to determine if they correctly identified those patients who would consistently fail (i.e., {>=}20% of fractions) during the course of their radiotherapy. Results: Six parameters were studied; the rectal volume (RV) and bladder volumes (BV) (in mL) received {>=}100% and {>=}70% of the prescribed dose and maximum dose to 2 mL of the rectum and bladder. This was given by RV{sub 100}, RV{sub 70}, BV{sub 100}, BV{sub 70}, RD{sub max}, and BD{sub max}, respectively. When more than 1 of the first 3 fractions exceed the planning constraint as defined, it accurately predicts consistent failures through the course of the treatment. This method is able to correctly identify the consistent failures about 80% (RV{sub 70}, BV{sub 100}, and RV{sub 100}), 90% (BV{sub 70}), and 100% (RD{sub max} and BD{sub max}) of the times. Conclusions: This study demonstrates the feasibility of a method accurately identifying patients who are likely to consistently exceed the planning constraints during the course of their treatment, using information from the first 3 to 5 fractions.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sugano, Yasutaka; Mizuta, Masahiro; Takao, Seishin

Purpose: Radiotherapy of solid tumors has been performed with various fractionation regimens such as multi- and hypofractionations. However, the ability to optimize the fractionation regimen considering the physical dose distribution remains insufficient. This study aims to optimize the fractionation regimen, in which the authors propose a graphical method for selecting the optimal number of fractions (n) and dose per fraction (d) based on dose–volume histograms for tumor and normal tissues of organs around the tumor. Methods: Modified linear-quadratic models were employed to estimate the radiation effects on the tumor and an organ at risk (OAR), where the repopulation of themore » tumor cells and the linearity of the dose-response curve in the high dose range of the surviving fraction were considered. The minimization problem for the damage effect on the OAR was solved under the constraint that the radiation effect on the tumor is fixed by a graphical method. Here, the damage effect on the OAR was estimated based on the dose–volume histogram. Results: It was found that the optimization of fractionation scheme incorporating the dose–volume histogram is possible by employing appropriate cell surviving models. The graphical method considering the repopulation of tumor cells and a rectilinear response in the high dose range enables them to derive the optimal number of fractions and dose per fraction. For example, in the treatment of prostate cancer, the optimal fractionation was suggested to lie in the range of 8–32 fractions with a daily dose of 2.2–6.3 Gy. Conclusions: It is possible to optimize the number of fractions and dose per fraction based on the physical dose distribution (i.e., dose–volume histogram) by the graphical method considering the effects on tumor and OARs around the tumor. This method may stipulate a new guideline to optimize the fractionation regimen for physics-guided fractionation.« less

Structural analysis of binding functionality of folic acid-PEG dendrimers against folate receptor.

PubMed

Sampogna-Mireles, Diana; Araya-Durán, Ingrid D; Márquez-Miranda, Valeria; Valencia-Gallegos, Jesús A; González-Nilo, Fernando D

2017-03-01

Dendrimers functionalized with folic acid (FA) are drug delivery systems that can selectively target cancer cells with folate receptors (FR-α) overexpression. Incorporation of polyethylene glycol (PEG) can enhance dendrimers solubility and pharmacokinetics, but ligand-receptor binding must not be affected. In this work we characterized, at atomic level, the binding functionality of conventional site-specific dendrimers conjugated with FA with PEG 750 or PEG 3350 as a linker. After Molecular Dynamics simulation, we observed that both PEG's did not interfere over ligand-receptor binding functionality. Although binding kinetics could be notably affected, the folate fragment from both dendrimers remained exposed to the solvent before approaching selectively to FR-α. PEG 3350 provided better solubility and protection from enzymatic degradation to the dendrimer than PEG 750. Also, FA-PEG3350 dendrimer showed a slightly better interaction with FR-α than FA-PEG750 dendrimer. Therefore, theoretical evidence supports that both dendrimers are suitable as drug delivery systems for cancer therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

Lignin-based polyoxyethylene ether enhanced enzymatic hydrolysis of lignocelluloses by dispersing cellulase aggregates.

PubMed

Lin, Xuliang; Qiu, Xueqing; Yuan, Long; Li, Zihao; Lou, Hongming; Zhou, Mingsong; Yang, Dongjie

2015-06-01

Water-soluble lignin-based polyoxyethylene ether (EHL-PEG), prepared from enzymatic hydrolysis lignin (EHL) and polyethylene glycol (PEG1000), was used to improve enzymatic hydrolysis efficiency of corn stover. The glucose yield of corn stover at 72h was increased from 16.7% to 70.1% by EHL-PEG, while increase in yield with PEG4600 alone was 52.3%. With the increase of lignin content, EHL-PEG improved enzymatic hydrolysis of microcrystalline cellulose more obvious than PEG4600. EHL-PEG could reduce at least 88% of the adsorption of cellulase on the lignin film measured by quartz crystal microbalance with dissipation monitoring (QCM-D), while reduction with PEG4600 was 43%. Cellulase aggregated at 1220nm in acetate buffer analyzed by dynamic light scattering. EHL-PEG dispersed cellulase aggregates and formed smaller aggregates with cellulase, thereby, reduced significantly nonproductive adsorption of cellulase on lignin and enhanced enzymatic hydrolysis of lignocelluloses. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nanosized self-emulsifying lipid vesicles of diacylglycerol-PEG lipid conjugates: Biophysical characterization and inclusion of lipophilic dietary supplements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koynova, Rumiana; Tihova, Mariana; Biopharma)

Hydrated diacylglycerol-PEG lipid conjugates, glyceryl dioleate-PEG12 (GDO-PEG12) and glyceryl dipalmitate-PEG23 (GDP-PEG23), spontaneously form uni- or oligolamellar liposomes in their liquid crystalline phase, in distinct difference from the PEGylated phospholipids which form micelles. GDP-PEG23 exhibits peculiar hysteretic phase behavior and can arrange into a long-living hexagonal phase at ambient and physiological temperatures. Liposomes of GDO-PEG12 and its mixture with soy lecithin exchange lipids with the membranes much more actively than common lecithin liposomes; such an active lipid exchange might facilitate the discharging of the liposome cargo upon uptake and internalization, and can thus be important in drug delivery applications. Diacylglycerol-PEG lipidmore » liposome formulations can encapsulate up to 20-30 wt.% lipophilic dietary supplements such as fish oil, coenzyme Q10, and vitamins D and E. The encapsulation is feasible by way of dry mixing, avoiding the use of organic solvent.« less

Generation, characterization and in vivo biological activity of two distinct monoclonal anti-PEG IgMs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hashimoto, Yosuke; Shimizu, Taro; Mima, Yu

PEGylation, the attachment of polyethylene glycol (PEG) to nanocarriers and proteins, is a widely accepted approach to improving the in vivo efficacy of the non-PEGylated products. However, both PEGylated liposomes and PEGylated proteins reportedly trigger the production of specific antibodies, mainly IgM, against the PEG moiety, which possibly leads to a reduction in safety and therapeutic efficacy of the PEGylated products. In the present study, two monoclonal anti-PEG IgMs — HIK-M09 via immunization with an intravenous injection of PEGylated liposomes (SLs) and HIK-M11 via immunization with a subcutaneous administration of PEGylated ovalbumin (PEG-OVA) were successfully generated. The generated IgMs showedmore » efficient reactivity to mPEG{sub 2000} conjugated to 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine (DSPE), PEGylated liposome (SL) and PEG-OVA. It appears that HIK-M09 recognizes ethoxy (OCH{sub 2}CH{sub 2}) repeat units along with a terminal motif of PEG, while HIK-M11 recognizes only ethoxy repeat units of PEG. Such unique properties allow HIK-M09 to bind with dense PEG. In addition, their impact on the in vivo clearance of the PEGylated products was investigated. It was found that the generated ant-PEG IgMs induced a clearance of SL as they were intravenously administered with SL. Interestingly, the HIK-M11, generated by PEG-OVA, induced the clearance of both SL and PEG-OVA, while the HIK-M09, generated by SL, induced the clearance of SL only. We here revealed that the presence of serum anti-PEG IgM and the subsequent binding of anti-PEG IgM to the PEGylated products are not necessarily related to the enhanced clearance of the products. It appears that subsequent complement activation following anti-PEG IgM binding is the most important step in dictating the in vivo fate of PEGylated products. This study may have implications for the design, development and clinical application of PEGylated products and therapeutics. - Highlights: • Two monoclonal anti-PEG IgMs were generated against distinct PEGylated materials. • In vivo cross-reactivity to the immunized materials was limited. • Although in vitro cross-reactivity of generated monoclonal IgMs has been confirmed.« less

Single endoscopist-performed percutaneous endoscopic gastrostomy tube placement

PubMed Central

Erdogan, Askin

2013-01-01

AIM: To investigate whether single endoscopist-performed percutaneous endoscopic gastrostomy (PEG) is safe and to compare the complications of PEG with those reported in the literature. METHODS: Patients who underwent PEG placement between June 2001 and August 2011 at the Baskent University Alanya Teaching and Research Center were evaluated retrospectively. Patients whose PEG was placed for the first time by a single endoscopist were enrolled in the study. PEG was performed using the pull method. All of the patients were evaluated for their indications for PEG, major and minor complications resulting from PEG, nutritional status, C-reactive protein (CRP) levels and the use of antibiotic treatment or antibiotic prophylaxis prior to PEG. Comorbidities, rates, time and reasons for mortality were also evaluated. The reasons for PEG removal and PEG duration were also investigated. RESULTS: Sixty-two patients underwent the PEG procedure for the first time during this study. Eight patients who underwent PEG placement by 2 endoscopists were not enrolled in the study. A total of 54 patients were investigated. The patients’ mean age was 69.9 years. The most common indication for PEG was cerebral infarct, which occurred in approximately two-thirds of the patients. The mean albumin level was 3.04 ± 0.7 g/dL, and 76.2% of the patients’ albumin levels were below the normal values. The mean CRP level was high in 90.6% of patients prior to the procedure. Approximately two-thirds of the patients received antibiotics for either prophylaxis or treatment for infections prior to the PEG procedure. Mortality was not related to the procedure in any of the patients. Buried bumper syndrome was the only major complication, and it occurred in the third year. In such case, the PEG was removed and a new PEG tube was placed via surgery. Eight patients (15.1%) experienced minor complications, 6 (11.1%) of which were wound infections. All wound infections except one recovered with antibiotic treatment. Two patients had bleeding from the PEG site, one was resolved with primary suturing and the other with fresh frozen plasma transfusion. CONCLUSION: The incidence of major and minor complications is in keeping with literature. This finding may be noteworthy, especially in developing countries. PMID:23864780

Rheological and thermal properties of polylactide/silicate nanocomposites films.

PubMed

Ahmed, Jasim; Varshney, Sunil K; Auras, Rafeal

2010-03-01

Polylactide (DL)/polyethylene glycol/silicate nanocomposite blended biodegradable films have been prepared by solvent casting method. Rheological and thermal properties were investigated for both neat amorphous polylactide (PLA-DL form) and blend of montmorillonite (clay) and poly (ethylene glycol) (PEG). Melt rheology of the PLA individually and blends (PLA/clay; PLA/PEG; PLA/PEG/clay) were performed by small amplitude oscillation shear (SAOS) measurement. Individually, PLA showed an improvement in the viscoelastic properties in the temperature range from 180 to 190 degrees C. Incorporation of nanoclay (3% to 9% wt) was attributed by significant improvements in the elastic modulus (G') of PLA/clay blend due to intercalation at higher temperature. Both dynamic modulii of PLA/PEG blend were significantly reduced with addition of 10% PEG. Rheometric measurement could not be conducted while PLA/PEG blends containing 25% PEG. A blend of PLA/PEG/clay (68/23/9) showed liquid-like properties with excellent flexibility. Thermal analysis of different clay loading films indicated that the glass transition temperatures (T(g)) remained unaffected irrespective of clay concentration due to immobilization of polymer chain in the clay nanocomposite. PEG incorporation reduced the T(g) of the blend (PLA/PEG and PLA/PEG/clay) significantly. Both rheological and thermal analysis data supported plasticization and flexibility of the blended films. It is also interesting to study competition between PLA and PEG for the intercalation into the interlayer spacing of the clay. This study indicates that PLA/montmorillonite blend could serve as effective nano-composite for packaging and other applications.

Systemic administration of a PEGylated adenovirus vector with a cancer-specific promoter is effective in a mouse model of metastasis.

PubMed

Yao, X; Yoshioka, Y; Morishige, T; Eto, Y; Watanabe, H; Okada, Y; Mizuguchi, H; Mukai, Y; Okada, N; Nakagawa, S

2009-12-01

Cancer gene therapy by adenovirus vectors (Advs) for metastatic cancer is limited because systemic administration of Adv produces low therapeutic effect and severe side effects. In this study, we generated a dual cancer-specific targeting vector system by using PEGylation and the telomere reverse transcriptase (TERT) promoter and attempted to treat experimental metastases through systemic administration of the vectors. We first optimized the molecular size of PEG and modification ratios used to create PEG-Ads. Systemic administration of PEG-Ad with 20-kDa PEG at a 45% modification ratio (PEG[20K/45%]-Ad) resulted in higher tumor-selective transgene expression than unmodified Adv. Next, we examined the effectiveness against metastases and side effects of a TERT promoter-driven PEG[20K/45%]-Ad containing the herpes simplex virus thymidine kinase (HSVtk) gene (PEG-Ad-TERT/HSVtk). Systemic administration of PEG-Ad-TERT/HSVtk showed superior antitumor effects against metastases with negligible side effects. A cytomegalovirus (CMV) promoter-driven PEG[20K/45%]-Ad also produced antimetastatic effects, but these were accompanied by side effects. Combining PEG-Ad-TERT/HSVtk with etoposide or 5-fluorouracil enhanced the therapeutic effects with negligible side effects. These results suggest that modification with 20-kDa PEG at a 45% modification ratio is the optimal condition for PEGylation of Adv, and PEG-Ad-TERT/HSVtk is a prototype Adv for systemic cancer gene therapy against metastases.

Physical characterization of polyethylene glycols by thermal analytical technique and the effect of humidity and molecular weight.

PubMed

Majumdar, R; Alexander, K S; Riga, A T

2010-05-01

Polyethylene glycols (PEGs) are well known as excipients in tablet dosage formulations. PEGs are generally known to be inert and have very few interactions with other components in the solid dosage forms. However, the physical nature of PEGs and how they affect the disintegration of tablets is not very well understood for the different molecular weights of PEGs. The knowledge of the effect of molecular weight of PEGs on their physical properties and the effect of humidity on the physical properties of PEGs are important parameters for the choice of a PEG to be acceptable as an excipient in pharmaceutical formulations. This study was done to determine the precision of the DSC physical properties for a wide range of PEGs with varying molecular weights from 194 to 23000 daltons. Nine different molecular weights of PEGs were examined in a DSC controlled Heat-Cool-Heat-Cool-Heat (HCHCH) cycle and the observed reproducible values of melting temperature, heat of fusion, crystallization temperature and the heat of crystallization were compared with values obtained from the literature and the observed percent crystallinity was again cross-checked by X-ray Diffraction (XRD) studies. The comparison values indicated acceptable precision. This study was also done to check the effect of humidity on the DSC physical properties for the entire range of PEGs. The results indicated that humidity probably has a higher effect on the physical properties of the low molecular weight PEGs as compared to the high molecular weight PEGs.

Co-delivery of doxorubicin and curcumin by pH-sensitive prodrug nanoparticle for combination therapy of cancer

NASA Astrophysics Data System (ADS)

Zhang, Yumin; Yang, Cuihong; Wang, Weiwei; Liu, Jinjian; Liu, Qiang; Huang, Fan; Chu, Liping; Gao, Honglin; Li, Chen; Kong, Deling; Liu, Qian; Liu, Jianfeng

2016-02-01

Ample attention has focused on cancer drug delivery via prodrug nanoparticles due to their high drug loading property and comparatively lower side effects. In this study, we designed a PEG-DOX-Cur prodrug nanoparticle for simultaneous delivery of doxorubicin (DOX) and curcumin (Cur) as a combination therapy to treat cancer. DOX was conjugated to PEG by Schiff’s base reaction. The obtained prodrug conjugate could self-assemble in water at pH 7.4 into nanoparticles (PEG-DOX NPs) and encapsulate Cur into the core through hydrophobic interaction (PEG-DOX-Cur NPs). When the PEG-DOX-Cur NPs are internalized by tumor cells, the Schiff’s base linker between PEG and DOX would break in the acidic environment that is often observed in tumors, causing disassembling of the PEG-DOX-Cur NPs and releasing both DOX and Cur into the nuclei and cytoplasma of the tumor cells, respectively. Compared with free DOX, free Cur, free DOX-Cur combination, or PEG-DOX NPs, PEG-DOX-Cur NPs exhibited higher anti-tumor activity in vitro. In addition, the PEG-DOX-Cur NPs also showed prolonged blood circulation time, elevated local drug accumulation and increased tumor penetration. Enhanced anti-tumor activity was also observed from the PEG-DOX-Cur-treated animals, demonstrating better tumor inhibitory property of the NPs. Thus, the PEG-DOX-Cur prodrug nanoparticle system provides a simple yet efficient approach of drug delivery for chemotherapy.

Matrix-array 3-dimensional echocardiographic assessment of volumes, mass, and ejection fraction in young pediatric patients with a functional single ventricle: a comparison study with cardiac magnetic resonance.

PubMed

Soriano, Brian D; Hoch, Martin; Ithuralde, Alejandro; Geva, Tal; Powell, Andrew J; Kussman, Barry D; Graham, Dionne A; Tworetzky, Wayne; Marx, Gerald R

2008-04-08

Quantitative assessment of ventricular volumes and mass in pediatric patients with single-ventricle physiology would aid clinical management, but it is difficult to obtain with 2-dimensional echocardiography. The purpose of the present study was to compare matrix-array 3-dimensional echocardiography (3DE) measurements of single-ventricle volumes, mass, and ejection fraction with those measured by cardiac magnetic resonance (CMR) in young patients. Twenty-nine patients (median age, 7 months) with a functional single ventricle undergoing CMR under general anesthesia were prospectively enrolled. The 3DE images were acquired at the conclusion of the CMR. Twenty-seven of 29 3DE data sets (93%) were optimal for 3DE assessment. Two blinded and independent observers performed 3DE measurements of volume, mass, and ejection fraction. The 3DE end-diastolic volume correlated well (r=0.96) but was smaller than CMR by 9% (P<0.01), and 3DE ejection fraction was smaller than CMR by 11% (P<0.01). There was no significant difference in measurements of end-systolic volume and mass. The 3DE interobserver differences for mass and volumes were not significant except for ejection fraction (8% difference; P<0.05). Intraobserver differences were not significant. In young pediatric patients with a functional single ventricle, matrix-array 3DE measurements of mass and volumes compare well with those obtained by CMR. 3DE will provide an important modality for the serial analysis of ventricular size and performance in young patients with functional single ventricles.

PEG-asparaginase induced severe hypertriglyceridemia.

PubMed

Galindo, Rodolfo J; Yoon, Justin; Devoe, Craig; Myers, Alyson K

2016-04-01

Asparaginase (ASP) is an effective chemotherapy agent extensively used in children with acute lymphocytic leukemia (ALL). There has been a recent interest in using ASP in adults with ALL, particularly the less toxic pegylated (PEG) formulation. Hypertriglyceridemia (HTG) is a rare complication of PEG-ASP therapy. We report two cases of obese patients who developed severe HTG after receiving PEG for ALL. Both patients were incidentally found to have severe HTG (TG of 4,330 and 4,420 mg/dL). In both patients, there was no personal or family history of dyslipidemia or hypothyroidism. There was no evidence of pancreatitis or skin manifestations of HTG. Both patients were treated with PEG cessation, low-fat diet and pharmacotherapy. Both patients were re-challenged with PEG, with subsequent increase in TG but no associated complications. TG returned to baseline after discontinuing PEG and while on therapy for HTG. A literature review of PEG-induced HTG in adults demonstrated similar results: asymptomatic presentation despite very severe HTG. HTG is a rare but clinically important adverse effect of PEG. Underlying obesity and/or diabetes may represent risk factors. Clinicians should monitor TG levels during PEG therapy to avoid TG-induced pancreatitis.

Treatment with mPEG-SPA improves the survival of corneal grafts in rats by immune camouflage.

PubMed

Wang, Shuangyong; Li, Liangliang; Liu, Ying; Li, Chaoyang; Zhang, Min; Wang, Bowen; Huang, Zheqian; Gao, Xinbo; Wang, Zhichong

2015-03-01

We investigated the immune camouflage effects of methoxy polyethylene glycol succinimidyl propionate (mPEG-SPA) on corneal antigens and explored a novel approach for reducing corneal antigenicity, thereby decreasing corneal graft rejection. Importantly, this approach did not alter normal local immunity. Corneal grafts were treated with mPEG-SPA 5KD or 20KD (3% W/V), which could shield major histocompatibility antigen class I molecules (RT1-A) of corneal grafts. Skin grafts of Wistar rats were transplanted to SD rats. Then the splenic lymphocytes were isolated from SD rats. Subsequently, the lymphocytes were co-cultured with autologous corneal grafts or untreated corneal grafts and PEGylated grafts treated with mPEG-SPA 5KD or 20KD obtained from the counterpart skin donors, which were used as autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group, respectively. Lymphocyte proliferation was lower in mPEG-SPA 5KD group and mPEG-SPA 20KD group than in the allogeneic control. SD rats with corneal neovascularisation were used as recipients for high-risk corneal transplantation and were randomly divided into four groups: autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group. The recipients received corneal grafts from Wistar rats. Corneal graft survival was prolonged and graft rejection was reduced in the mPEG-SPA 5KD group and the mPEG-SPA 20KD group compared to the allogeneic control. Thus, we think that mPEG-SPA could immunologically camouflage corneal antigens to prolong corneal grafts survival in high-risk transplantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Inhibition of HeLa cell growth by doxorubicin-loaded and tuftsin-conjugated arginate-PEG microparticles.

PubMed

Hu, Tianmu; Qahtan, Anwar Saeed Ahmed; Lei, Lei; Lei, Zhixin; Zhao, Dapeng; Nie, Hemin

2018-03-01

In order to improve the release pattern of chemotherapy drug and reduce the possibility of drug resistance, poly(ethylene glycol amine) (PEG)-modified alginate microparticles (ALG-PEG MPs) were developed then two different mechanisms were employed to load doxorubicin (Dox): 1) forming Dox/ALG-PEG complex by electrostatic attractions between unsaturated functional groups in Dox and ALG-PEG; 2) forming Dox-ALG-PEG complex through EDC-reaction between the amino and carboxyl groups in Dox and ALG, respectively. Additionally, tuftsin (TFT), a natural immunomodulation peptide, was conjugated to MPs in order to enhance the efficiency of cellular uptake. It was found that the Dox-ALG-PEG-TFT MPs exhibited a significantly slower release of Dox than Dox/ALG-PEG-TFT MPs in neutral medium, suggesting the role of covalent bonding in prolonging Dox retention. Besides, the release of Dox from these MPs was pH-sensitive, and the release rate was observably increased at pH 6.5 compared to the case at pH 7.4. Compared with Dox/ALG-PEG MPs and Dox-ALG-PEG MPs, their counterparts further conjugated with TFT more efficiently inhibited the growth of HeLa cells over a period of 48 h, implying the effectiveness of TFT in enhancing cellular uptake of MPs. Over a period of 48 h, Dox-ALG-PEG-TFT MPs inhibited the growth of HeLa cells less efficiently than Dox/ALG-PEG-TFT MPs but the difference was not significant ( p  > 0.05). In consideration of the prolonged and sustained release of Dox, Dox-ALG-PEG-TFT MPs possess the advantages for long-term treatment.

Impact of large aggregated uricases and PEG diol on accelerated blood clearance of PEGylated canine uricase.

PubMed

Zhang, Chun; Fan, Kai; Ma, Xuefeng; Wei, Dongzhi

2012-01-01

Uricase has proven therapeutic value in treating hyperuricemia but sufficient reduction of its immunogenicity may be the largest obstacle to its chronic use. In this study, canine uricase was modified with 5 kDa mPEG-SPA and the impact of large aggregated uricases and cross-linked conjugates induced by difunctional PEG diol on immunogenicity was investigated. Recombinant canine uricase was first expressed and purified to homogeneity. Source 15Q anion-exchange chromatography was used to separate tetrameric and aggregated uricase prior to pegylation, while DEAE anion-exchange chromatography was used to remove Di-acid PEG (precursor of PEG diol) from unfractionated 5 kDa mPEG-propionic acid. Tetrameric and aggregated uricases were separately modified with the purified mPEG-SPA. In addition, tetrameric uricases was modified with unfractionated mPEG-SPA, resulting in three types of 5 kDa mPEG-SPA modified uricase. The conjugate size was evaluated by dynamic light scattering and transmission electron microscope. The influence of differently PEGylated uricases on pharmacokinetics and immunogenicity were evaluated in vivo. The accelerated blood clearance (ABC) phenomenon previously identified for PEGylated liposomes occurred in rats injected with PEGylated uricase aggregates. Anti-PEG IgM antibodies, rather than neutralizing antibodies, were found to mediate the ABC. The size of conjugates is important for triggering such phenomena and we speculate that 40-60 nm is the lower size limit that can trigger ABC. Removal of the uricase aggregates and the PEG diol contaminant and modifying with small PEG reagents enabled ABC to be successfully avoided and sufficient reduction in the immunogenicity of 5 kDa mPEG-modified tetrameric canine uricase.

Impact of Large Aggregated Uricases and PEG Diol on Accelerated Blood Clearance of PEGylated Canine Uricase

PubMed Central

Zhang, Chun; Fan, Kai; Ma, Xuefeng; Wei, Dongzhi

2012-01-01

Background Uricase has proven therapeutic value in treating hyperuricemia but sufficient reduction of its immunogenicity may be the largest obstacle to its chronic use. In this study, canine uricase was modified with 5 kDa mPEG-SPA and the impact of large aggregated uricases and cross-linked conjugates induced by difunctional PEG diol on immunogenicity was investigated. Methods and Findings Recombinant canine uricase was first expressed and purified to homogeneity. Source 15Q anion-exchange chromatography was used to separate tetrameric and aggregated uricase prior to pegylation, while DEAE anion-exchange chromatography was used to remove Di-acid PEG (precursor of PEG diol) from unfractionated 5 kDa mPEG-propionic acid. Tetrameric and aggregated uricases were separately modified with the purified mPEG-SPA. In addition, tetrameric uricases was modified with unfractionated mPEG-SPA, resulting in three types of 5 kDa mPEG-SPA modified uricase. The conjugate size was evaluated by dynamic light scattering and transmission electron microscope. The influence of differently PEGylated uricases on pharmacokinetics and immunogenicity were evaluated in vivo. The accelerated blood clearance (ABC) phenomenon previously identified for PEGylated liposomes occurred in rats injected with PEGylated uricase aggregates. Anti-PEG IgM antibodies, rather than neutralizing antibodies, were found to mediate the ABC. Conclusions The size of conjugates is important for triggering such phenomena and we speculate that 40–60 nm is the lower size limit that can trigger ABC. Removal of the uricase aggregates and the PEG diol contaminant and modifying with small PEG reagents enabled ABC to be successfully avoided and sufficient reduction in the immunogenicity of 5 kDa mPEG-modified tetrameric canine uricase. PMID:22745806

Physicochemical characterization of spray-dried PLGA/PEG microspheres, and preliminary assessment of biological response.

PubMed

Javiya, Curie; Jonnalagadda, Sriramakamal

2016-09-01

The use of spray-drying to prepare blended PLGA:PEG microspheres with lower immune detection. To study physical properties, polymer miscibility and alveolar macrophage response for blended PLGA:PEG microspheres prepared by a laboratory-scale spray-drying process. Microspheres were prepared by spray-drying 0-20% w/w ratios of PLGA 65:35 and PEG 3350 in dichloromethane. Particle size and morphology was studied using scanning electron microscopy. Polymer miscibility and residual solvent levels evaluated by thermal analysis (differential scanning calorimetry - DSC and thermogravimetric analysis - TGA). Immunogenicity was assessed in vitro by response of rat alveolar macrophages (NR8383) by the MTT-based cell viability assay and reactive oxygen species (ROS) detection. The spray dried particles were spherical, with a size range of about 2-3 µm and a yield of 16-60%. Highest yield was obtained at 1% PEG concentration. Thermal analysis showed a melting peak at 59 °C (enthalpy: 170.61 J/g) and a degradation-onset of 180 °C for PEG 3350. PLGA 65:35 was amorphous, with a Tg of 43 °C. Blended PLGA:PEG microspheres showed a delayed degradation-onset of 280 °C, and PEG enthalpy-loss corresponding to 15% miscibility of PEG in PLGA. NR8383 viability studies and ROS detection upon exposure to these cells suggested that blended PLGA:PEG microspheres containing 1 and 5% PEG are optimal in controling cell proliferation and activation. This research establishes the feasibility of using a spray-drying process to prepare spherical particles (2-3 µm) of molecularly-blended PLGA 65:35 and PEG 3350. A PEG concentration of 1-5% was optimal to maximize process yield, with minimal potential for immune detection.

Cost-effectiveness analysis of sofosbuvir plus peginterferon/ribavirin in the treatment of chronic hepatitis C virus genotype 1 infection.

PubMed

Saab, S; Gordon, S C; Park, H; Sulkowski, M; Ahmed, A; Younossi, Z

2014-09-01

Sofosbuvir, an oral NS5B nucleotide polymerase inhibitor, is indicated for the treatment of patients infected with hepatitis C virus (HCV). To evaluate the long-term health economic outcomes of sofosbuvir + pegylated interferon alfa/ribavirin (pegIFN/RBV) compared with current treatments in patients infected with HCV genotype 1 in the US. A decision-analytic Markov model was developed to estimate health outcomes, number needed to treat and short-term and long-term economic outcomes, including incremental cost-effectiveness ratios and cost per sustained virological response (SVR), for several sofosbuvir-comparator regimen pairings for a cohort of 10 000 patients. It considered three patient cohorts: treatment-naïve, treatment-experienced and treatment-naïve human immunodeficiency virus (HIV) co-infected. Subgroup analyses were conducted for treatment-naïve patients with and without cirrhosis. Reductions in the incidence of new cases of liver-disease complications with sofosbuvir + pegIFN/RBV compared with pegIFN/RBV, boceprevir + pegIFN/RBV, telaprevir + pegIFN/RBV and simeprevir + pegIFN/RBV were 64-82%, 50-68%, 43-58% and 33-56%, respectively. Sofosbuvir + pegIFN/RBV was typically associated with the lowest 1-year cost per SVR. When considering the lifetime incremental cost per quality-adjusted life-year gained, sofosbuvir + pegIFN/RBV was the most cost-effective treatment option assessed. Sofosbuvir + pegIFN/RBV generally dominated (less costly and more effective than) boceprevir + pegIFN/RBV, telaprevir + pegIFN/RBV and simeprevir + pegIFN/RBV. Sofosbuvir + pegIFN/RBV yields more favourable future health and economic outcomes than current treatment regimens for patients across all levels of treatment experience and cirrhosis stage, as well as for individuals with or without HIV co-infection. © 2014 John Wiley & Sons Ltd.

Minority race and male sex as risk factors for non-beneficial gastrostomy tube placements after stroke.

PubMed

Faigle, Roland; Carrese, Joseph A; Cooper, Lisa A; Urrutia, Victor C; Gottesman, Rebecca F

2018-01-01

Percutaneous endoscopic gastrostomy (PEG) tubes are widely used for enteral feeding after stroke; however, PEG tubes placed in patients in whom death is imminent are considered non-beneficial. We sought to determine whether placement of non-beneficial PEG tubes differs by race and sex. In this retrospective cohort study, inpatient admissions for stroke patients who underwent palliative/withdrawal of care, were discharged to hospice, or died during the hospitalization, were identified from the Nationwide Inpatient Sample between 2007 and 2011. Logistic regression was used to evaluate the association between race and sex with PEG placement. Of 36,109 stroke admissions who underwent palliative/withdrawal of care, were discharge to hospice, or experienced in-hospital death, a PEG was placed in 2,258 (6.3%). Among PEG recipients 41.1% were of a race other than white, while only 22.0% of patients without PEG were of a minority race (p<0.001). The proportion of men was higher among those with compared to without a PEG tube (50.0% vs. 39.2%, p<0.001). Minority race was associated with PEG placement compared to whites (OR 1.75, 95% CI 1.57-1.96), and men had 1.27 times higher odds of PEG compared to women (95% CI 1.16-1.40). Racial differences were most pronounced among women: ethnic/racial minority women had over 2-fold higher odds of a PEG compared to their white counterparts (OR 2.09, 95% CI 1.81-2.41), while male ethnic/racial minority patients had 1.44 increased odds of a PEG when compared to white men (95% CI 1.24-1.67, p-value for interaction <0.001). Minority race and male sex are risk factors for non-beneficial PEG tube placements after stroke.

Soot volume fraction fields in unsteady axis-symmetric flames by continuous laser extinction technique.

PubMed

Kashif, Muhammad; Bonnety, Jérôme; Guibert, Philippe; Morin, Céline; Legros, Guillaume

2012-12-17

A Laser Extinction Method has been set up to provide two-dimensional soot volume fraction field time history at a tunable frequency up to 70 Hz inside an axis-symmetric diffusion flame experiencing slow unsteady phenomena preserving the symmetry. The use of a continuous wave laser as the light source enables this repetition rate, which is an incremental advance in the laser extinction technique. The technique is shown to allow a fine description of the soot volume fraction field in a flickering flame exhibiting a 12.6 Hz flickering phenomenon. Within this range of repetition rate, the technique and its subsequent post-processing require neither any method for time-domain reconstruction nor any correction for energy intrusion. Possibly complemented by such a reconstruction method, the technique should support further soot volume fraction database in oscillating flames that exhibit characteristic times relevant to the current efforts in the validation of soot processes modeling.

Feasibility of Reducing the Fiber Content in Ultra-High-Performance Fiber-Reinforced Concrete under Flexure.

PubMed

Park, Jung-Jun; Yoo, Doo-Yeol; Park, Gi-Joon; Kim, Sung-Wook

2017-01-28

In this study, the flexural behavior of ultra-high-performance fiber-reinforced concrete (UHPFRC) is examined as a function of fiber length and volume fraction. Straight steel fiber with three different lengths ( l f ) of 13, 19.5, and 30 mm and four different volume fractions ( v f ) of 0.5%, 1.0%, 1.5%, and 2.0% are considered. Test results show that post-cracking flexural properties of UHPFRC, such as flexural strength, deflection capacity, toughness, and cracking behavior, improve with increasing fiber length and volume fraction, while first-cracking properties are not significantly influenced by fiber length and volume fraction. A 0.5 vol % reduction of steel fiber content relative to commercial UHPFRC can be achieved without deterioration of flexural performance by replacing short fibers ( l f of 13 mm) with longer fibers ( l f of 19.5 mm and 30 mm).

Feasibility of Reducing the Fiber Content in Ultra-High-Performance Fiber-Reinforced Concrete under Flexure

PubMed Central

Park, Jung-Jun; Yoo, Doo-Yeol; Park, Gi-Joon; Kim, Sung-Wook

2017-01-01

In this study, the flexural behavior of ultra-high-performance fiber-reinforced concrete (UHPFRC) is examined as a function of fiber length and volume fraction. Straight steel fiber with three different lengths (lf) of 13, 19.5, and 30 mm and four different volume fractions (vf) of 0.5%, 1.0%, 1.5%, and 2.0% are considered. Test results show that post-cracking flexural properties of UHPFRC, such as flexural strength, deflection capacity, toughness, and cracking behavior, improve with increasing fiber length and volume fraction, while first-cracking properties are not significantly influenced by fiber length and volume fraction. A 0.5 vol % reduction of steel fiber content relative to commercial UHPFRC can be achieved without deterioration of flexural performance by replacing short fibers (lf of 13 mm) with longer fibers (lf of 19.5 mm and 30 mm). PMID:28772477

Effective Thermal Conductivity of an Aluminum Foam + Water Two Phase System

NASA Technical Reports Server (NTRS)

Moskito, John

1996-01-01

This study examined the effect of volume fraction and pore size on the effective thermal conductivity of an aluminum foam and water system. Nine specimens of aluminum foam representing a matrix of three volume fractions (4-8% by vol.) and three pore sizes (2-4 mm) were tested with water to determine relationships to the effective thermal conductivity. It was determined that increases in volume fraction of the aluminum phase were correlated to increases in the effective thermal conductivity. It was not statistically possible to prove that changes in pore size of the aluminum foam correlated to changes in the effective thermal conductivity. However, interaction effects between the volume fraction and pore size of the foam were statistically significant. Ten theoretical models were selected from the published literature to compare against the experimental data. Models by Asaad, Hadley, and de Vries provided effective thermal conductivity predictions within a 95% confidence interval.

Electric-field-dependent phase volume fractions and enhanced piezoelectricity near the polymorphic phase boundary of (K0.5Na0.5)1-xLixNbO3 textured ceramics

NASA Astrophysics Data System (ADS)

Ge, Wenwei; Li, Jiefang; Viehland, D.; Chang, Yunfei; Messing, Gary L.

2011-06-01

The structure, ferroelectric and piezoelectric properties of <001> textured (K0.5Na0.5)0.98Li0.02NbO3 ceramics were investigated as a function of temperature and dc bias E. X-ray diffraction revealed an orthorhombic (O) → tetragonal (T) polymorphic phase boundary (PPB). Phase coexistence was found near the PPB over a 30 °C temperature range, where the relative phase volume fractions changed with temperature. Furthermore, increasing E applied along the <001> texture direction resulted in a notable increase in the volume fraction of the T phase at the expense of the O phase, effectively shifting the O → T boundary to lower temperature. An enhancement in the piezoelectric properties was found to accompany this increase in the T volume fraction.

Laser-induced incandescence calibration via gravimetric sampling

NASA Technical Reports Server (NTRS)

Choi, M. Y.; Vander Wal, R. L.; Zhou, Z.

1996-01-01

Absolute calibration of laser-induced incandescence (LII) is demonstrated via comparison of LII signal intensities with gravimetrically determined soot volume fractions. This calibration technique does not rely upon calculated or measured optical characteristics of soot. The variation of the LII signal with gravimetrically measured soot volume fractions ranging from 0.078 to 1.1 ppm established the linearly of the calibration. With the high spatial and temporal resolution capabilities of laser-induced incandescence (LII), the spatial and temporal fluctuations of the soot field within a gravimetric chimney were characterized. Radial uniformity of the soot volume fraction, f(sub v) was demonstrated with sufficient averaging of the single laser-shot LII images of the soot field thus confirming the validity of the calibration method for imaging applications. As illustration, instantaneous soot volume fractions within a Re = 5000 ethylene/air diffusion flame measured via planar LII were established quantitatively with this calibration.

Antidiabetic Activity of Self Nanoemulsifying Drug Delivery System from Bay Leaves (Eugenia polyantha Wight) Ethyl Acetate Fraction

NASA Astrophysics Data System (ADS)

Prihapsara, F.; Harini, M.; Widiyani, T.; Artanti, A. N.; Ani, I. L.

2017-02-01

Insulin resistance is caused by inability of target tissues to insulin response. Bay leaves (Eugenia polyantha Wight) fraction or extract have been used for the treatment of antidibetic mellitus type-2 resistance insulin (ADMRI) but it has low solubility and bioavailability. To overcome these problems, ethyl acetate fraction of bay leaves was formulated into self nanoemulsifying drug delivery system (SNEDDS) using Virgin Coconut Oil (VCO) as a carrier oil. This study aims to produce nanoherbal medicine, determine effect of nanoherbal preparation derived from bay leaves as an anti-ADMRI. The results showed that the optimum SNEDDS formula was tween 80 : PEG 400 : Virgin Coconut Oil (30% : 60% : 10%) in 5 mL. It has emulsification time 13.00 seconds with the average of droplet size value 84.5 nanometer and zeta potential value ± 0.2 mV. Morphological observation showed the nanoemulsion particles has spherical shaped and stable in different pH media. Hypoglycaemic effect of single dose metformin, SNEDDS, combination a-half dose of SNEEDS with metformin value is 28.3%; 15.6%; 34.6% respectively.

Characteristics and cytotoxicity of folate-modified curcumin-loaded PLA-PEG micellar nano systems with various PLA:PEG ratios.

PubMed

Phan, Quoc Thong; Le, Mai Huong; Le, Thi Thu Huong; Tran, Thi Hong Ha; Xuan, Phuc Nguyen; Ha, Phuong Thu

2016-06-30

Targeting delivery system use natural drugs for tumor cells is an appealing platform help to reduce the side effects and enhance the therapeutic effects of the drug. In this study, we synthesized curcumin (Cur) loaded (D, L Poly lactic - Poly ethylenglycol) micelle (Cur/PLA-PEG) with the ratio of PLA/PEG of 3:1 2:1 1:1 1:2 and 1:3 (w/w) and another micelle modified by folate (Cur/PLA-PEG-Fol) for targeting cancer therapy. The PLA-PEG copolymer was synthesized by ring opening polymerization method. After loading onto the micelle, solubility of Cur increased from 0.38 to 0.73mgml(-1). The average size of prepared Cur/PLA-PEG micelles was from 60 to 69nm (corresponding to the ratio difference of PLA/PEG) and the drug encapsulating efficiency was from 48.8 to 91.3%. Compared with the Cur/PLA-PEG micelles, the size of Cur/PLA-PEG-Fol micelles were from 80 to 86nm and showed better in vitro cellular uptake and cytotoxicity towards HepG2 cells. The cytotoxicity of the NPs however depends much on the PEG component. The results demonstrated that Folate-modified micelles could serve as a potential nano carrier to improve solubility, anti-cancer activity of Cur and targeting ability of the system. Copyright © 2016 Elsevier B.V. All rights reserved.

Cardiac cycle-dependent left atrial dynamics: implications for catheter ablation of atrial fibrillation.

PubMed

Patel, Amit R; Fatemi, Omid; Norton, Patrick T; West, J Jason; Helms, Adam S; Kramer, Christopher M; Ferguson, John D

2008-06-01

Left atrial (LA) volume determines prognosis and response to therapy for atrial fibrillation. Integration of electroanatomic maps with three-dimensional images rendered from computed tomography and magnetic resonance imaging (MRI) is used to facilitate atrial fibrillation ablation. The purpose of this study was to measure LA volume changes and regional motion during the cardiac cycle that might affect the accuracy of image integration and to determine their relationship to standard LA volume measurements. MRI was performed in 30 patients with paroxysmal atrial fibrillation. LA time-volume curves were generated and used to divide LA ejection fraction into pumping ejection fraction and conduit ejection fraction and to determine maximum LA volume (LA(max)) and preatrial contraction volume. LA volume was measured using an MRI angiogram and traditional geometric models from echocardiography (area-length model and ellipsoid model). In-plane displacement of the pulmonary veins, anterior left atrium, mitral annulus, and LA appendage was measured. LA(max) was 107 +/- 36 mL and occurred at 42% +/- 5% of the R-R interval. Preatrial contraction volume was 86 +/- 34 mL and occurred at 81% +/- 4% of the R-R interval. LA ejection fraction was 45% +/- 10%, and pumping ejection fraction was 31% +/- 10%. LA volume measurements made from MRI angiogram, area-length model, and ellipsoid model underestimated LA(max) by 21 +/- 25 mL, 16 +/- 26 mL, and 35 +/- 22 mL, respectively. Anterior LA, mitral annulus, and LA appendage were significantly displaced during the cardiac cycle (8.8 +/- 2.0 mm, 13.2 +/- 3.8 mm, and 10.2 +/- 3.4 mm, respectively); the pulmonary veins were not displaced. LA volume changes significantly during the cardiac cycle, and substantial regional variation in LA motion exists. Standard measurements of LA volume significantly underestimate LA(max) compared to the gold standard measure of three-dimensional volumetrics.

Conditional internalization of PEGylated nanomedicines by PEG engagers for triple negative breast cancer therapy

NASA Astrophysics Data System (ADS)

Su, Yu-Cheng; Burnouf, Pierre-Alain; Chuang, Kuo-Hsiang; Chen, Bing-Mae; Cheng, Tian-Lu; Roffler, Steve R.

2017-06-01

Triple-negative breast cancer (TNBC) lacks effective treatment options due to the absence of traditional therapeutic targets. The epidermal growth factor receptor (EGFR) has emerged as a promising target for TNBC therapy because it is overexpressed in about 50% of TNBC patients. Here we describe a PEG engager that simultaneously binds polyethylene glycol and EGFR to deliver PEGylated nanomedicines to EGFR+ TNBC. The PEG engager displays conditional internalization by remaining on the surface of TNBC cells until contact with PEGylated nanocarriers triggers rapid engulfment of nanocargos. PEG engager enhances the anti-proliferative activity of PEG-liposomal doxorubicin to EGFR+ TNBC cells by up to 100-fold with potency dependent on EGFR expression levels. The PEG engager significantly increases retention of fluorescent PEG probes and enhances the antitumour activity of PEGylated liposomal doxorubicin in human TNBC xenografts. PEG engagers with specificity for EGFR are promising for improved treatment of EGFR+ TNBC patients.

Investigation of Micro- and Nanosized Particle Erosion in a 90° Pipe Bend Using a Two-Phase Discrete Phase Model

PubMed Central

Safaei, M. R.; Mahian, O.; Garoosi, F.; Hooman, K.; Karimipour, A.; Kazi, S. N.; Gharehkhani, S.

2014-01-01

This paper addresses erosion prediction in 3-D, 90° elbow for two-phase (solid and liquid) turbulent flow with low volume fraction of copper. For a range of particle sizes from 10 nm to 100 microns and particle volume fractions from 0.00 to 0.04, the simulations were performed for the velocity range of 5–20 m/s. The 3-D governing differential equations were discretized using finite volume method. The influences of size and concentration of micro- and nanoparticles, shear forces, and turbulence on erosion behavior of fluid flow were studied. The model predictions are compared with the earlier studies and a good agreement is found. The results indicate that the erosion rate is directly dependent on particles' size and volume fraction as well as flow velocity. It has been observed that the maximum pressure has direct relationship with the particle volume fraction and velocity but has a reverse relationship with the particle diameter. It also has been noted that there is a threshold velocity as well as a threshold particle size, beyond which significant erosion effects kick in. The average friction factor is independent of the particle size and volume fraction at a given fluid velocity but increases with the increase of inlet velocities. PMID:25379542

Magnetic susceptibility, artifact volume in MRI, and tensile properties of swaged Zr-Ag composites for biomedical applications.

PubMed

Imai, Haruki; Tanaka, Yoji; Nomura, Naoyuki; Doi, Hisashi; Tsutsumi, Yusuke; Ono, Takashi; Hanawa, Takao

2017-02-01

Zr-Ag composites were fabricated to decrease the magnetic susceptibility by compensating for the magnetic susceptibility of their components. The Zr-Ag composites with a different Zr-Ag ratio were swaged, and their magnetic susceptibility, artifact volume, and mechanical properties were evaluated by magnetic balance, three-dimensional (3-D) artifact rendering, and a tensile test, respectively. These properties were correlated with the volume fraction of Ag using the linear rule of mixture. We successfully obtained the swaged Zr-Ag composites up to the reduction ratio of 96% for Zr-4, 16, 36, 64Ag and 86% for Zr-81Ag. However, the volume fraction of Ag after swaging tended to be lower than that before swaging, especially for Ag-rich Zr-Ag composites. The magnetic susceptibility of the composites linearly decreased with the increasing volume fraction of Ag. No artifact could be estimated with the Ag volume fraction in the range from 93.7% to 95.4% in three conditions. Young's modulus, ultimate tensile strength (UTS), and 0.2% yield strength of Zr-Ag composites showed slightly lower values compared to the estimated values using a linear rule of mixture. The decrease in magnetic susceptibility of Zr and Ag by alloying or combining would contribute to the decrease of the Ag fraction, leading to the improvement of mechanical properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

An optimized strategy to measure protein stability highlights differences between cold and hot unfolded states

NASA Astrophysics Data System (ADS)

Alfano, Caterina; Sanfelice, Domenico; Martin, Stephen R.; Pastore, Annalisa; Temussi, Piero Andrea

2017-05-01

Macromolecular crowding ought to stabilize folded forms of proteins, through an excluded volume effect. This explanation has been questioned and observed effects attributed to weak interactions with other cell components. Here we show conclusively that protein stability is affected by volume exclusion and that the effect is more pronounced when the crowder's size is closer to that of the protein under study. Accurate evaluation of the volume exclusion effect is made possible by the choice of yeast frataxin, a protein that undergoes cold denaturation above zero degrees, because the unfolded form at low temperature is more expanded than the corresponding one at high temperature. To achieve optimum sensitivity to changes in stability we introduce an empirical parameter derived from the stability curve. The large effect of PEG 20 on cold denaturation can be explained by a change in water activity, according to Privalov's interpretation of cold denaturation.

31P NMR spectroscopy studies of phospholipid metabolism in human melanoma xenograft lines differing in rate of tumour cell proliferation.

PubMed

Lyng, H; Olsen, D R; Petersen, S B; Rofstad, E K

1995-04-01

The concentration of phospholipid metabolites in tumours has been hypothesized to be related to rate of cell membrane turnover and may reflect rate of cell proliferation. The purpose of the study reported here was to investigate whether 31P NMR resonance ratios involving the phosphomonoester (PME) or phosphodiester (PDE) resonance are correlated to fraction of cells in S-phase or volume-doubling time in experimental tumours. Four human melanoma xenograft lines (BEX-t, HUX-t, SAX-t, WIX-t) were included in the study. The tumours were grown subcutaneously in male BALB/c-nu/nu mice. 31P NMR spectroscopy was performed at a magnetic field strength of 4.7 T. Fraction of cells in S-phase was measured by flow cytometry. Tumour volume-doubling time was determined by Gompertzian analysis of volumetric growth data. BEX-t and SAX-t tumours differed in fraction of cells in S-phase and volume-doubling time, but showed similar 31P NMR resonance ratios. BEX-t and WIX-t tumours showed significantly different 31P NMR resonance ratios but similar fractions of cells in S-phase. The 31P NMR resonance ratios were significantly different for small and large HUX-t tumours even though fraction of cells in S-phase and volume-doubling time did not differ with tumour volume. None of the 31P NMR resonance ratios showed significant increase with increasing fraction of cells in S-phase or significant decrease with increasing tumour volume-doubling time across the four xenograft lines.(ABSTRACT TRUNCATED AT 250 WORDS)

Soot Volume Fraction Maps for Normal and Reduced Gravity Laminar Acetylene Jet Diffusion Flames

NASA Technical Reports Server (NTRS)

Greenberg, Paul S.; Ku, Jerry C.

1997-01-01

The study of soot particulate distribution inside gas jet diffusion flames is important to the understanding of fundamental soot particle and thermal radiative transport processes, as well as providing findings relevant to spacecraft fire safety, soot emissions, and radiant heat loads for combustors used in air-breathing propulsion systems. Compared to those under normal gravity (1-g) conditions, the elimination of buoyancy-induced flows is expected to significantly change the flow field in microgravity (O g) flames, resulting in taller and wider flames with longer particle residence times. Work by Bahadori and Edelman demonstrate many previously unreported qualitative and semi-quantitative results, including flame shape and radiation, for sooting laminar zas jet diffusion flames. Work by Ku et al. report soot aggregate size and morphology analyses and data and model predictions of soot volume fraction maps for various gas jet diffusion flames. In this study, we present the first 1-g and 0-g comparisons of soot volume fraction maps for laminar acetylene and nitrogen-diluted acetylene jet diffusion flames. Volume fraction is one of the most useful properties in the study of sooting diffusion flames. The amount of radiation heat transfer depends directly on the volume fraction and this parameter can be measured from line-of-sight extinction measurements. Although most Soot aggregates are submicron in size, the primary particles (20 to 50 nm in diameter) are in the Rayleigh limit, so the extinction absorption) cross section of aggregates can be accurately approximated by the Rayleigh solution as a function of incident wavelength, particles' complex refractive index, and particles' volume fraction.

S. pombe CLASP needs dynein, not EB1 or CLIP170, to induce microtubule instability and slows polymerization rates at cell tips in a dynein-dependent manner

PubMed Central

Grallert, Agnes; Beuter, Christoph; Craven, Rachel A.; Bagley, Steve; Wilks, Deepti; Fleig, Ursula; Hagan, Iain M.

2006-01-01

The Schizosaccharomyces pombe CLIP170-associated protein (CLASP) Peg1 was identified in a screen for mutants with spindle formation defects and a screen for molecules that antagonized EB1 function. The conditional peg1.1 mutant enabled us to identify key features of Peg1 function. First, Peg1 was required to form a spindle and astral microtubules, yet destabilized interphase microtubules. Second, Peg1 was required to slow the polymerization rate of interphase microtubules that establish end-on contact with the cortex at cell tips. Third, Peg1 antagonized the action of S. pombe CLIP170 (Tip1) and EB1 (Mal3). Fourth, although Peg1 resembled higher eukaryotic CLASPs by physically associating with both Mal3 and Tip1, neither Tip1 nor Mal3 was required for Peg1 to destabilize interphase microtubules or for it to associate with microtubules. Conversely, neither Mal3 nor Tip1 required Peg1 to associate with microtubules or cell tips. Consistently, while mal3.Δ and tip1.Δ disrupted linear growth, corrupting peg1 + did not. Fifth, peg1.1 phenotypes resembled those arising from deletion of the single heavy or both light chains of fission yeast dynein. Furthermore, all interphase phenotypes arising from peg1 + manipulation relied on dynein function. Thus, the impact of S. pombe CLASP on interphase microtubule behavior is more closely aligned to dynein than EB1 or CLIP170. PMID:16951255

[Grain Size Distribution Characteristics of Suspended Particulate Matter as Influenced by the Apparent Pollution in the Eutrophic Urban Landscape Water Body].

PubMed

Gong, Dan-yan; Pan, Yang; Huang, Yong; Bao, Wei; Li, Qian-qian

2016-03-15

Grain size distribution characteristics of suspended particulate matter (SPM) reflects the apparent polluted condition of the urban landscape water. In order to explore the internal relationship between the eutrophication of urban landscape water's apparent pollution and grain size distribution of SPM, and its influencing factors, this paper selected five representative sampling sites in Feng Jin River which is a typical eutrophication river in Suzhou City, measured the grain size distribution of SPM, sensation pollution index (SPI) and water quality index, and analyzed their correlation. The results showed that: The rich nutrient water possessed a similar characteristics in grain size distribution. The grain size distribution of SPM in water was multimodal, and the the peak position was roughly the same; the grain size distribution of SPM was composed by multiple components. It could be roughly divided into six parts with the particle size range of every group being < 1.5 µm, 1.5-8 µm, 8-35 µm, 35-186 µm, 186-516 µm, > 516 µm. The component III was superior (with an average volume fraction of 38.3%-43.2%), and its volume fraction had a significant positive relation with the SPI value and the Chl-a content. The increase of component III volume fraction was the reflection of particle size's result of increasing SPI value. The increase of component III volume fraction was mainly derived from the increasing algal content. The volume fraction of group IV + group VI + group V was significantly higher under the condition of exogenous enter. When there was no exogenous component, the volume fraction of group IV + group VI + group V had a significant negative correlation with SPI value; when there were exogenous components, the volume fraction of group IV + group VI + group V had a weak positive correlation with SPI value, but the correlation did not reach a significant level. Environmental factors (Fv/Fm and DO) and exogenous factors had an influence by functioning on the algal content which signified the polluted material, and then affected the volume fraction of particle size's components and the quality of apparent water. Hydrodynamic conditions mainly had a certain influence on the median particle size, and had no effect on the apparent polluted condition of water.

Effect of the molecular structure of lignin-based polyoxyethylene ether on enzymatic hydrolysis efficiency and kinetics of lignocelluloses.

PubMed

Lin, Xuliang; Qiu, Xueqing; Zhu, Duming; Li, Zihao; Zhan, Ningxin; Zheng, Jieyi; Lou, Hongming; Zhou, Mingsong; Yang, Dongjie

2015-10-01

Effect of the molecular structure of lignin-based polyoxyethylene ether (EHL-PEG) on enzymatic hydrolysis of Avicel and corn stover was investigated. With the increase of PEG contents and molecular weight of EHL-PEG, glucose yield of corn stover increased. EHL-PEG enhanced enzymatic hydrolysis of corn stover significantly at buffer pH 4.8-5.5. Glucose yield of corn stover at 20% solid content increased from 32.8% to 63.8% by adding EHL-PEG, while that with PEG4600 was 54.2%. Effect of EHL-PEG on enzymatic hydrolysis kinetics of cellulose film was studied by quartz crystal microbalance with dissipation monitoring (QCM-D) and atomic force microscopy (AFM). An enhancing mechanism of EHL-PEG on enzymatic hydrolysis kinetics of cellulose was proposed. Cellulase aggregates dispersed by EHL-PEG excavated extensive cavities into the surface of cellulose film, making the film become more loose and exposed. After the maximum enzymatic hydrolysis rate, the film was mainly peeled off layer by layer until equilibrium. Copyright © 2015 Elsevier Ltd. All rights reserved.

Complete regression of xenograft tumors using biodegradable mPEG-PLA-SN38 block copolymer micelles.

PubMed

Lu, Lu; Zheng, Yan; Weng, Shuqiang; Zhu, Wenwei; Chen, Jinhong; Zhang, Xiaomin; Lee, Robert J; Yu, Bo; Jia, Huliang; Qin, Lunxiu

2016-06-01

7-Ethyl-10-hydroxy-comptothecin (SN38) is an active metabolite of irinotecan (CPT-11) and the clinical application of SN38 is limited by its hydrophobicity and instability. To address these issues, a series of novel amphiphilic mPEG-PLA-SN38-conjugates were synthesized by linking SN38 to mPEG-PLA-SA, and they could form micelles by self-assembly. The effects of mPEG-PLA composition were studied in vitro and in vivo. The mean diameters of mPEG2K-PLA-SN38 micelles and mPEG4K-PLA-SN38 micelles were 10-20nm and 120nm, respectively, and mPEG2K-PLA-SN38 micelles showed greater antitumor efficacy than mPEG4K-PLA-SN38 micelles both in vitro and in vivo. These data suggest that the lengths of mPEG and PLA chains had a major impact on the physicochemical characteristics and antitumor activity of SN38-conjugate micelles. Copyright © 2016 Elsevier B.V. All rights reserved.

The exploration of endocytic mechanisms of PLA-PEG nanoparticles prepared by coaxialtri-capillary electrospray-template removal method.

PubMed

Chen, Jiaming; Cao, Lihua; Cui, Yuecheng; Tu, Kehua; Wang, Hongjun; Wang, Li-Qun

2018-01-01

The nano-sized poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) particles with core-shell structure were efficiently prepared by using coaxial tri-capillary electrospray-template removal method. The cellular uptake mechanism, intracellular distribution and exocytosis in A549 cell model of electrosprayed PLA-PEG nanoparticles were systemically studied. The drug release behavior of electrosprayed PLA-PEG nanoparticles were also investigated. Our results showed that PLA-PEG nanoparticles can be endocytosed quickly by A549 cells. The cellular uptake of PLA-PEG nanoparticles was an energy dependent endocytosis process. Caveolae-mediated endocytosis was only one of endocytosis pathways in A549 cells for PLA-PEG nanoparticles, while clathrin mediated endocytosis was not involved in the endocytosis process. The endocytosed PLA-PEG nanoparticles enriched in the head of A549 cells and only a small amount of them was transported into lysosome after 24h incubation. These findings provided insights into the application of electrosprayed PLA-PEG nanoparticles in nano drug delivery field. Copyright © 2017 Elsevier B.V. All rights reserved.

Safety of polyethylene glycol 3350 for the treatment of chronic constipation in children.

PubMed

Pashankar, Dinesh S; Loening-Baucke, Vera; Bishop, Warren P

2003-07-01

To assess the clinical and biochemical safety profile of long-term polyethylene glycol 3350 (PEG) therapy in children with chronic constipation and to assess pediatric patient acceptance of PEG therapy. Prospective observational study. Pediatric clinics at a referral center. Patients Eighty-three children (44 with chronic constipation, 39 with constipation and encopresis) receiving PEG therapy for more than 3 months. Clinical adverse effects related to PEG therapy and acceptance and compliance with PEG therapy. Serum electrolyte levels, osmolality, albumin levels, and liver and renal function test results were measured. At the time of evaluation, the mean duration of PEG therapy was 8.7 months, and the mean PEG dose was 0.75 g/kg daily. There were no major clinical adverse effects. All blood test results were normal, except for transient minimal alanine aminotransferase elevation unrelated to therapy in 9 patients. All children preferred PEG to previously used laxatives, and daily compliance was measured as good in 90% of children. Long-term PEG therapy is safe and is well accepted by children with chronic constipation with and without encopresis.

Standard filtration practices may significantly distort planktonic microbial diversity estimates.

PubMed

Padilla, Cory C; Ganesh, Sangita; Gantt, Shelby; Huhman, Alex; Parris, Darren J; Sarode, Neha; Stewart, Frank J

2015-01-01

Fractionation of biomass by filtration is a standard method for sampling planktonic microbes. It is unclear how the taxonomic composition of filtered biomass changes depending on sample volume. Using seawater from a marine oxygen minimum zone, we quantified the 16S rRNA gene composition of biomass on a prefilter (1.6 μm pore-size) and a downstream 0.2 μm filter over sample volumes from 0.05 to 5 L. Significant community shifts occurred in both filter fractions, and were most dramatic in the prefilter community. Sequences matching Vibrionales decreased from ~40 to 60% of prefilter datasets at low volumes (0.05-0.5 L) to less than 5% at higher volumes, while groups such at the Chromatiales and Thiohalorhabdales followed opposite trends, increasing from minor representation to become the dominant taxa at higher volumes. Groups often associated with marine particles, including members of the Deltaproteobacteria, Planctomycetes, and Bacteroidetes, were among those showing the greatest increase with volume (4 to 27-fold). Taxon richness (97% similarity clusters) also varied significantly with volume, and in opposing directions depending on filter fraction, highlighting potential biases in community complexity estimates. These data raise concerns for studies using filter fractionation for quantitative comparisons of aquatic microbial diversity, for example between free-living and particle-associated communities.

Influence of structure on radiation shielding effectiveness of graphite fiber reinforced polyethylene composite

NASA Astrophysics Data System (ADS)

Emmanuel, A.; Raghavan, J.

2015-10-01

While LEO and GEO are used for most satellite missions, Highly Elliptical Orbits (HEOs) are also used for satellite missions covering Polar Regions of Earth. Satellites in HEO are exposed to a relatively harsher radiation environment than LEO and GEO. The mass of traditionally used aluminum radiation shield, required to attenuate the radiation to a level below a certain threshold that is safe for the satellite bus and payload, scales with the level of radiation. It has been shown (Emmanuel et al., 2014) that materials with low atomic number (Z) such as polyethylene (PE) can result in a lighter shield than aluminum (Al) in HEO. However, PE has to be reinforced with relatively high Z fibers such as graphite (G) to improve its mechanical properties. The effect of introduction of G and the resulting composite structure (that meets the requirements on mechanical properties, manufacturing and service) on the radiation shielding effectiveness of PE was studied through simulation using a layered PE-G composite. The Total Ionization Dose (TID), deposited in a silicon detector behind the composite shield, has been found to be function of layer volume fraction, layer thickness and stacking sequence of the PE and G layers. One composite configuration has resulted in a TID lower than that for PE, demonstrating the possibility of tailoring the mechanical properties of PE-based composite radiation shield with minimal negative impact on its radiation shielding effectiveness.

MSAll strategy for comprehensive quantitative analysis of PEGylated-doxorubicin, PEG and doxorubicin by LC-high resolution q-q-TOF mass spectrometry coupled with all window acquisition of all fragment ion spectra.

PubMed

Yin, Lei; Su, Chong; Ren, Tianming; Meng, Xiangjun; Shi, Meiyun; Paul Fawcett, J; Zhang, Mengliang; Hu, Wei; Gu, Jingkai

2017-11-06

The covalent attachment of polyethylene glycol (PEG) to therapeutic compounds (known as PEGylation) is one of the most promising techniques to improve the biological efficacy of small molecular weight drugs. After administration, PEGylated prodrugs can be metabolized into pharmacologically active compounds so that PEGylated drug, free drug and released PEG are present simultaneously in the body. Understanding the pharmacokinetic behavior of these three compounds is needed to guide the development of pegylated theranostic agents. However, PEGs are polydisperse molecules with a wide range of molecular weights, so that the simultaneous quantitation of PEGs and PEGylated molecules in biological matrices is very challenging. This article reports the application of a data-independent acquisition method (MS All ) based on liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (LC-q-q-TOF-MS) in the positive ion mode to the simultaneous determination of methoxyPEG2000-doxorubicin (mPEG2K-Dox) and its breakdown products in rat blood. Using the MS All technique, precursor ions of all molecules are generated in q1, fragmented to product ions in q2 (collision cell), and subjected to TOF separation before precursor and product ions are recorded using low and high collision energies (CE) respectively in different experiments for a single sample injection. In this study, dissociation in q2 generated a series of high resolution PEG-related product ions at m/z 89.0611, 133.0869, 177.1102, 221.1366, 265.1622, 309.1878, and 353.2108 corresponding to fragments containing various numbers of ethylene oxide subunits, Dox-related product ions at m/z 321.0838 and 361.0785, and an mPEG2K-Dox specific product ion at m/z 365.0735. Detection of mPEGs and mPEG2K-Dox was based on high resolution extracted ions of mPEG and the specific compound. The method was successfully applied to a pharmacokinetic study of doxorubicin, mPEG2K (methylated polyethylene glycol 2K), and mPEG2K-doxorubicin in rats after a single intravenous injection of mPEG2K-doxorubicin. To the best of our knowledge, this is the first assay that simultaneously determines mPEG, Dox, and mPEG2K-Dox in a biological matrix. We believe the MS All technique as applied in this study can be potentially extended to the determination of other PEGylated small molecules or polymeric compounds.

Glucose-functionalized Au nanoprisms for optoacoustic imaging and near-infrared photothermal therapy

NASA Astrophysics Data System (ADS)

Han, Jishu; Zhang, Jingjing; Yang, Meng; Cui, Daxiang; de La Fuente, Jesus M.

2015-12-01

Targeted imaging and tumor therapy using nanomaterials has stimulated research interest recently, but the high cytotoxicity and low cellular uptake of nanomaterials limit their bioapplication. In this paper, glucose (Glc) was chosen to functionalize Au nanoprisms (NPrs) for improving the cytotoxicity and cellular uptake of Au@PEG-Glc NPrs into cancer cells. Glucose is a primary source of energy at the cellular level and at cellular membranes for cell recognition. A coating of glucose facilitates the accumulation of Au@PEG-Glc NPrs in a tumor region much more than Au@PEG NPrs. Due to the high accumulation and excellent photoabsorbing property of Au@PEG-Glc NPrs, enhanced optoacoustic imaging of a tumor in vivo was achieved, and visualization of the tumor further guided cancer treatment. Based on the optical-thermal conversion performance of Au@PEG-Glc NPrs, the tumor in vivo was effectively cured through photothermal therapy. The current work demonstrates the great potential of Au@PEG-Glc NPrs in optoacoustic imaging and photothermal cancer therapy in future.Targeted imaging and tumor therapy using nanomaterials has stimulated research interest recently, but the high cytotoxicity and low cellular uptake of nanomaterials limit their bioapplication. In this paper, glucose (Glc) was chosen to functionalize Au nanoprisms (NPrs) for improving the cytotoxicity and cellular uptake of Au@PEG-Glc NPrs into cancer cells. Glucose is a primary source of energy at the cellular level and at cellular membranes for cell recognition. A coating of glucose facilitates the accumulation of Au@PEG-Glc NPrs in a tumor region much more than Au@PEG NPrs. Due to the high accumulation and excellent photoabsorbing property of Au@PEG-Glc NPrs, enhanced optoacoustic imaging of a tumor in vivo was achieved, and visualization of the tumor further guided cancer treatment. Based on the optical-thermal conversion performance of Au@PEG-Glc NPrs, the tumor in vivo was effectively cured through photothermal therapy. The current work demonstrates the great potential of Au@PEG-Glc NPrs in optoacoustic imaging and photothermal cancer therapy in future. Electronic supplementary information (ESI) available: The evolution of the UV-vis absorption of Au NPrs by centrifugation, TEM image of PEG-capped Au NPrs, the UV-vis absorption of glucose, cytotoxicity of Au@PEG-Glc NPrs, gastric cell viabilities versus the concentration of Au@PEG-Glc NPrs and gastric cell viabilities filled with 80 μg Au@PEG-Glc NPrs versus the irradiation time, optoacoustic signals of Au NPr solution and Au@PEG NPrs. See DOI: 10.1039/c5nr06261f

Analytical functions for beta and gamma absorbed fractions of iodine-131 in spherical and ellipsoidal volumes.

PubMed

Mowlavi, Ali Asghar; Fornasier, Maria Rossa; Mirzaei, Mohammd; Bregant, Paola; de Denaro, Mario

2014-10-01

The beta and gamma absorbed fractions in organs and tissues are the important key factors of radionuclide internal dosimetry based on Medical Internal Radiation Dose (MIRD) approach. The aim of this study is to find suitable analytical functions for beta and gamma absorbed fractions in spherical and ellipsoidal volumes with a uniform distribution of iodine-131 radionuclide. MCNPX code has been used to calculate the energy absorption from beta and gamma rays of iodine-131 uniformly distributed inside different ellipsoids and spheres, and then the absorbed fractions have been evaluated. We have found the fit parameters of a suitable analytical function for the beta absorbed fraction, depending on a generalized radius for ellipsoid based on the radius of sphere, and a linear fit function for the gamma absorbed fraction. The analytical functions that we obtained from fitting process in Monte Carlo data can be used for obtaining the absorbed fractions of iodine-131 beta and gamma rays for any volume of the thyroid lobe. Moreover, our results for the spheres are in good agreement with the results of MIRD and other scientific literatures.

Conducting polymer actuator based on chemically deposited polypyrrole and polyurethane-based solid polymer electrolyte working in air

NASA Astrophysics Data System (ADS)

Choi, Hwa-Jeong; Song, Young-Min; Chung, Ildoo; Ryu, Kwang-Sun; Jo, Nam-Ju

2009-02-01

Conducting polymers (CPs), such as polypyrrole, polythiophene, and polyaniline, are unique in that they have switchable properties due to their two or more mechanically stable oxidation states. Thus, their films or coatings can be easily switched by the application of a small voltage and current to change their volume during electrochemical redox processes. In particular, polypyrrole (PPy) has been studied most extensively because of its high electrical conductivity and good environmental stability under ambient conditions. In this work, we have studied a new CP actuator, fully polymeric, assembled with two PPy film electrodes and a solid polymer electrolyte (SPE), polyurethane/Mg(ClO4)2. Polyurethanes (PUs) were synthesized from 4,4'-diphenylmethane diisocyanate (MDI), 1,4-butanediol (1,4-BD) and three types of polyol: poly(ethylene glycol) (PEG), poly(propylene glycol) (PPG), and PPG-block-PEG-block-PPG (PPG-co-PEG). The chemical polymerization of PPy by immersion in Py monomer aqueous solution and oxidant aqueous solution is an adequate method to prepare PU/PPy composite film as an actuator. To find the proper thickness of the PPy coating layer for actuation, we measured the displacements of the actuators according to the thickness of the PPy coating layer. The displacement of all actuators is discussed in connection with the properties of the SPE and PPy. All the results obtained in this work show the feasibility of electrochemomechanical devices based on PPy and SPE film being able to work in air.

IgY Technology: Extraction of Chicken Antibodies from Egg Yolk by Polyethylene Glycol (PEG) Precipitation

PubMed Central

Pauly, Diana; Chacana, Pablo A.; Calzado, Esteban G.; Brembs, Björn; Schade, Rüdiger

2011-01-01

Hens can be immunized by means of i.m. vaccination (Musculus pectoralis, left and right, injection volume 0.5-1.0 ml) or by means of Gene-Gun plasmid-immunization. Dependent on the immunogenicity of the antigen, high antibody-titres (up to 1:100,000 - 1:1,000,000) can be achieved after only one or 3 - 4 boost immunizations. Normally, a hen lays eggs continuously for about 72 weeks, thereafter the laying capacity decreases. This protocol describes the extraction of total IgY from egg yolk by means of a precipitation procedure (PEG. Polson et al. 1980). The method involves two important steps. The first one is the removal of lipids and the second is the precipitation of total IgY from the supernatant of step one. After dialysis against a buffer (normally PBS) the IgY-extract can be stored at -20°C for more than a year. The purity of the extract is around 80 %, the total IgY per egg varies from 40-80 mg, dependent on the age of the laying hen. The total IgY content increases with the age of the hen from around 40 mg/egg up to 80 mg/egg (concerning PEG precipitation). The laying capacity of a hen per year is around 325 eggs. That means a total potential harvest of 20 g total IgY/year based on a mean IgY content of 60 mg total IgY/egg (see Table 1). PMID:21559009

Dual-Functional Ultrafiltration Membrane for Simultaneous Removal of Multiple Pollutants with High Performance.

PubMed

Pan, Shunlong; Li, Jiansheng; Noonan, Owen; Fang, Xiaofeng; Wan, Gaojie; Yu, Chengzhong; Wang, Lianjun

2017-05-02

Simultaneous removal of multiple pollutants from aqueous solution with less energy consumption is crucial in water purification. Here, a novel concept of dual-functional ultrafiltration (DFUF) membrane is demonstrated by entrapment of nanostructured adsorbents into the finger-like pores of ultrafiltration (UF) membrane rather than in the membrane matrix in previous reports of blend membranes, resulting in an exceptionally high active content and simultaneous removal of multiple pollutants from water due to the dual functions of rejection and adsorption. As a demonstration, hollow porous Zr(OH) x nanospheres (HPZNs) were immobilized in poly(ether sulfone) (PES) UF membranes through polydopamine coating with a high content of 68.9 wt %. The decontamination capacity of DFUF membranes toward multiple model pollutants (colloidal gold, polyethylene glycol (PEG), Pb(II)) was evaluated against a blend membrane. Compared to the blend membrane, the DFUF membranes showed 2.1-fold increase in the effective treatment volume for the treatment of Pb(II) contaminated water from 100 ppb to below 10 ppb (WHO drinking water standard). Simultaneously, the DFUF membranes effectively removed the colloidal gold and PEG below instrument detection limit, however the blend membrane only achieved 97.6% and 96.8% rejection for colloidal gold and PEG, respectively. Moreover, the DFUF membranes showed negligible leakage of nanoadsorbents during testing; and the membrane can be easily regenerated and reused. This study sheds new light on the design of high performance multifunction membranes for drinking water purification.

Preparation of poly(ethylene glycol) hydrogels with different network structures for the application of enzyme immobilization.

PubMed

Choi, Dongkil; Lee, Woojin; Park, Jinwon; Koh, Wongun

2008-01-01

In this study, poly(ethylene glycol) (PEG)-based hydrogels having different network structures were synthesized by UV-initiated photopolymerization and used for the enzyme immobilization. PEGs with different molecular weight were acrylated by derivatizing both ends with acryloyl chloride and photopolymerization of PEG-diacrylate (PEG-DA) yielded crosslinked hydrogel network within 5 seconds. Attachment of acrylate groups and gelation were confirmed by ATR/FT-IR and FT-Raman spectroscopy. Network structures of hydrogels could be easily controlled by changing the molecular weight (MW) of PEG-DA and characterized by calculating molecular weight between crosslinks and mesh size from the swelling measurement. Synthesis of hydrogels with higher MW of PEG produced less crosslinked hydrogels having higher water content, larger value of Mc and mesh size, which resulted in enhanced mass transfer but loss of mechanical properties. For the enzyme immobilization, glucose oxidase (GOX) was immobilized inside PEG hydrogels by means of physical entrapment and covalent immobilization. Encapsulated GOX were covalently bound to PEG backbone using acryloyl-PEG-N-hydroxysuccinimide and maintained their activity over a week period without leakage. Kinetic study indicated that immobilized enzyme inside hydrogel prepared from higher MW of PEG possessed lower apparent Km (Michaelis-Menten constant) and higher activity.

PEG-lipid micelles as drug carriers: physiochemical attributes, formulation principles and biological implication.

PubMed

Gill, Kanwaldeep K; Kaddoumi, Amal; Nazzal, Sami

2015-04-01

PEG-lipid micelles, primarily conjugates of polyethylene glycol (PEG) and distearyl phosphatidylethanolamine (DSPE) or PEG-DSPE, have emerged as promising drug-delivery carriers to address the shortcomings associated with new molecular entities with suboptimal biopharmaceutical attributes. The flexibility in PEG-DSPE design coupled with the simplicity of physical drug entrapment have distinguished PEG-lipid micelles as versatile and effective drug carriers for cancer therapy. They were shown to overcome several limitations of poorly soluble drugs such as non-specific biodistribution and targeting, lack of water solubility and poor oral bioavailability. Therefore, considerable efforts have been made to exploit the full potential of these delivery systems; to entrap poorly soluble drugs and target pathological sites both passively through the enhanced permeability and retention (EPR) effect and actively by linking the terminal PEG groups with targeting ligands, which were shown to increase delivery efficiency and tissue specificity. This article reviews the current state of PEG-lipid micelles as delivery carriers for poorly soluble drugs, their biological implications and recent developments in exploring their active targeting potential. In addition, this review sheds light on the physical properties of PEG-lipid micelles and their relevance to the inherent advantages and applications of PEG-lipid micelles for drug delivery.

Beverage intake preference and bowel preparation laxative taste preference for colonoscopy

PubMed Central

Laiyemo, Adeyinka O; Burnside, Clinton; Laiyemo, Maryam A; Kwagyan, John; Williams, Carla D; Idowu, Kolapo A; Ashktorab, Hassan; Kibreab, Angesom; Scott, Victor F; Sanderson, Andrew K

2015-01-01

AIM: To examine whether non-alcoholic beverage intake preferences can guide polyethylene glycol (PEG)-based bowel laxative preparation selection for patients. METHODS: We conducted eight public taste test sessions using commercially procured (A) unflavored PEG, (B) citrus flavored PEG and (C) PEG with ascorbate (Moviprep). We collected characteristics of volunteers including their beverage intake preferences. The volunteers tasted the laxatives in randomly assigned orders and ranked the laxatives as 1st, 2nd, and 3rd based on their taste preferences. Our primary outcome is the number of 1st place rankings for each preparation. RESULTS: A total of 777 volunteers completed the study. Unflavored PEG was ranked as 1st by 70 (9.0%), flavored PEG by 534 (68.7%) and PEG with ascorbate by 173 (22.3%) volunteers. Demographic, lifestyle characteristics and beverage intake patterns for coffee, tea, and carbonated drinks did not predict PEG-based laxative preference. CONCLUSION: Beverage intake pattern was not a useful guide for PEG-based laxative preference. It is important to develop more tolerable and affordable bowel preparation laxatives for colonoscopy. Also, patients should taste their PEG solution with and without flavoring before flavoring the entire gallon as this may give them more opportunity to pick a pattern that may be more tolerable. PMID:26261736

Beverage intake preference and bowel preparation laxative taste preference for colonoscopy.

PubMed

Laiyemo, Adeyinka O; Burnside, Clinton; Laiyemo, Maryam A; Kwagyan, John; Williams, Carla D; Idowu, Kolapo A; Ashktorab, Hassan; Kibreab, Angesom; Scott, Victor F; Sanderson, Andrew K

2015-08-06

To examine whether non-alcoholic beverage intake preferences can guide polyethylene glycol (PEG)-based bowel laxative preparation selection for patients. We conducted eight public taste test sessions using commercially procured (A) unflavored PEG, (B) citrus flavored PEG and (C) PEG with ascorbate (Moviprep). We collected characteristics of volunteers including their beverage intake preferences. The volunteers tasted the laxatives in randomly assigned orders and ranked the laxatives as 1(st), 2(nd), and 3(rd) based on their taste preferences. Our primary outcome is the number of 1(st) place rankings for each preparation. A total of 777 volunteers completed the study. Unflavored PEG was ranked as 1(st) by 70 (9.0%), flavored PEG by 534 (68.7%) and PEG with ascorbate by 173 (22.3%) volunteers. Demographic, lifestyle characteristics and beverage intake patterns for coffee, tea, and carbonated drinks did not predict PEG-based laxative preference. Beverage intake pattern was not a useful guide for PEG-based laxative preference. It is important to develop more tolerable and affordable bowel preparation laxatives for colonoscopy. Also, patients should taste their PEG solution with and without flavoring before flavoring the entire gallon as this may give them more opportunity to pick a pattern that may be more tolerable.

PEGylation of Biopharmaceuticals: A Review of Chemistry and Nonclinical Safety Information of Approved Drugs.

PubMed

Turecek, Peter L; Bossard, Mary J; Schoetens, Freddy; Ivens, Inge A

2016-02-01

Modification of biopharmaceutical molecules by covalent conjugation of polyethylene glycol (PEG) molecules is known to enhance pharmacologic and pharmaceutical properties of proteins and other large molecules and has been used successfully in 12 approved drugs. Both linear and branched-chain PEG reagents with molecular sizes of up to 40 kDa have been used with a variety of different PEG derivatives with different linker chemistries. This review describes the properties of PEG itself, the history and evolution of PEGylation chemistry, and provides examples of PEGylated drugs with an established medical history. A trend toward the use of complex PEG architectures and larger PEG polymers, but with very pure and well-characterized PEG reagents is described. Nonclinical toxicology findings related to PEG in approved PEGylated biopharmaceuticals are summarized. The effect attributed to the PEG part of the molecules as observed in 5 of the 12 marketed products was cellular vacuolation seen microscopically mainly in phagocytic cells which is likely related to their biological function to absorb and remove particles and macromolecules from blood and tissues. Experience with marketed PEGylated products indicates that adverse effects in toxicology studies are usually related to the active part of the drug but not to the PEG moiety. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Recent development of poly(ethylene glycol)-cholesterol conjugates as drug delivery systems.

PubMed

He, Zhi-Yao; Chu, Bing-Yang; Wei, Xia-Wei; Li, Jiao; Edwards, Carl K; Song, Xiang-Rong; He, Gu; Xie, Yong-Mei; Wei, Yu-Quan; Qian, Zhi-Yong

2014-07-20

Poly(ethylene glycol)-cholesterol (PEG-Chol) conjugates are composed of "hydrophilically-flexible" PEG and "hydrophobically-rigid" Chol molecules. PEG-Chol conjugates are capable of forming micelles through molecular self-assembly and they are also used extensively for the PEGylation of drug delivery systems (DDS). The PEGylated DDS have been shown to display optimized physical stability properties in vitro and longer half-lives in vivo when compared with non-PEGylated DDS. Cell uptake studies have indicated that PEG-Chol conjugates are internalized via clathrin-independent pathways into endosomes and Golgi apparatus. Acid-labile PEG-Chol conjugates are also able to promote the content release of PEGylated DDS when triggered by dePEGylation at acidic conditions. More importantly, biodegradable PEG-Chol molecules have been shown to decrease the "accelerated blood clearance" phenomenon of PEG-DSPE. Ligands, peptides or antibodies which have been modified with PEG-Chols are oftentimes used to formulate active targeting DDS, which have been shown in many systems recently to enhance the efficacy and lower the adverse effects of drugs. Production of PEG-Chol is simple and efficient, and production costs are relatively low. In conclusion, PEG-Chol conjugates appear to be very promising multifunctional biomaterials for many uses in the biomedical sciences and pharmaceutical industries. Copyright © 2014 Elsevier B.V. All rights reserved.

New sterically stabilized vesicles based on nonionic surfactant, cholesterol, and poly(ethylene glycol)-cholesterol conjugates.

PubMed Central

Beugin, S; Edwards, K; Karlsson, G; Ollivon, M; Lesieur, S

1998-01-01

Monomethoxypoly(ethylene glycol) cholesteryl carbonates (M-PEG-Chol) with polymer chain molecular weights of 1000 (M-PEG1000-Chol) and 2000 (M-PEG2000-Chol) have been newly synthesized and characterized. Their aggregation behavior in mixture with diglycerol hexadecyl ether (C16G2) and cholesterol has been examined by cryotransmission electron microscopy, high-performance gel exclusion chromatography, and quasielastic light scattering. Nonaggregated, stable, unilamellar vesicles were obtained at low polymer levels with optimal shape and size homogeneity at cholesteryl conjugate/ lipids ratios of 10 mol% M-PEG1000-Chol or 5 mol% M-PEG2000-Chol, corresponding to the theoretically predicted brush conformational state of the PEG chains. At 20 mol% M-PEG1000-Chol or 10 mol% M-PEG2000-Chol, the saturation threshold of the C16G2/cholesterol membrane in polymer is exceeded, and open disk-shaped aggregates are seen in coexistence with closed vesicles. Higher levels up to 30 mol% lead to the complete solubilization of the vesicles into disk-like structures of decreasing size with increasing PEG content. This study underlines the bivalent role of M-PEG-Chol derivatives: while behaving as solubilizing surfactants, they provide an efficient steric barrier, preventing the vesicles from aggregation and fusion over a period of at least 2 weeks. PMID:9635773

Superparamagnetic nanoparticle clusters for cancer theranostics combining magnetic resonance imaging and hyperthermia treatment.

PubMed

Hayashi, Koichiro; Nakamura, Michihiro; Sakamoto, Wataru; Yogo, Toshinobu; Miki, Hirokazu; Ozaki, Shuji; Abe, Masahiro; Matsumoto, Toshio; Ishimura, Kazunori

2013-01-01

Superparamagnetic nanoparticles (SPIONs) could enable cancer theranostics if magnetic resonance imaging (MRI) and magnetic hyperthermia treatment (MHT) were combined. However, the particle size of SPIONs is smaller than the pores of fenestrated capillaries in normal tissues because superparamagnetism is expressed only at a particle size <10 nm. Therefore, SPIONs leak from the capillaries of normal tissues, resulting in low accumulation in tumors. Furthermore, MHT studies have been conducted in an impractical way: direct injection of magnetic materials into tumor and application of hazardous alternating current (AC) magnetic fields. To accomplish effective enhancement of MRI contrast agents in tumors and inhibition of tumor growth by MHT with intravenous injection and a safe AC magnetic field, we clustered SPIONs not only to prevent their leakage from fenestrated capillaries in normal tissues, but also for increasing their relaxivity and the specific absorption rate. We modified the clusters with folic acid (FA) and polyethylene glycol (PEG) to promote their accumulation in tumors. SPION clustering and cluster modification with FA and PEG were achieved simultaneously via the thiol-ene click reaction. Twenty-four hours after intravenous injection of FA- and PEG-modified SPION nanoclusters (FA-PEG-SPION NCs), they accumulated locally in cancer (not necrotic) tissues within the tumor and enhanced the MRI contrast. Furthermore, 24 h after intravenous injection of the NCs, the mice were placed in an AC magnetic field with H = 8 kA/m and f = 230 kHz (Hf = 1.8×10(9) A/m∙s) for 20 min. The tumors of the mice underwent local heating by application of an AC magnetic field. The temperature of the tumor was higher than the surrounding tissues by ≈6°C at 20 min after treatment. Thirty-five days after treatment, the tumor volume of treated mice was one-tenth that of the control mice. Furthermore, the treated mice were alive after 12 weeks; control mice died up to 8 weeks after treatment.

Whole-bowel irrigation for mechanical colon cleansing.

PubMed

Michael, K A; DiPiro, J T; Bowden, T A; Tedesco, F J

1985-01-01

The physiology, solution composition, indications, efficacy, and safety of whole-bowel irrigation (WBI) for mechanical bowel cleansing are reviewed. WBI with isotonic electrolyte solutions produces diarrhea when the infusion rate exceeds the capacity of the intestine to distend and absorb the solution. A number of solutions are used for WBI, including 0.9% sodium chloride, balanced electrolyte solutions, lactated Ringer's, mannitol, and electrolyte solutions containing polyethylene glycol 3350 (PEG). WBI solution administration rates vary from 15-90 mL/min, by oral ingestion or nasogastric tube, with total volumes ranging from 1 to 20 L. The onset of diarrhea occurs as soon as 20 minutes with clearing of the effluent as early as 90 minutes. Faster administration rates appear to shorten overall cleansing time. Two PEG-electrolyte lavage solutions (ELSs) have recently gained FDA approval. The recommended dosage rate is 1.2-1.8 L/hr orally or by nasogastric tube until rectal effluent is clear. In most patients, this requires a maximum of 4-6 L. Initial data indicate that PEG-ELSs are safe for elderly patients and for patients who have an increased risk of fluid overload, but these solutions have not been evaluated in children, pregnant women, or patients with inflammatory bowel disease. WBI is an effective alternative to other regimens for removing fecal material and reducing bowel lumen bacterial counts before colonoscopy and colorectal surgery. Retention of bacterial counts before colonoscopy and colorectal surgery. Retention of excess WBI solution may interfere with the quality of barium enema radiographs; this can be minimized by completing the irrigation the evening before the examination. Gastrointestinal side effects occur in about one third of the patients following WBI, but do not generally require discontinuing the irrigation. Solutions containing PEG with sodium sulfate as the primary electrolyte result in the least net water and electrolyte movement and are preferred over other solutions.

Developing and Evaluating In Vitro Effect of Poly(Ethylene Glycol) Conjugated Curcumin on Human Cancer Cell Lines.

PubMed

Tung, Bui Thanh; Hai, Nguyen Thanh; Son, Phan Ke

2016-01-01

Curcumin has been shown to possess strong cytotoxic effect against various cancer cell lines. However, curcumin has not applied as a drug for treatment of cancer yet due to low solubility in water and low bioavailability. The aims of this study were to prepare a new polyethylene glycol (PEG) conjugated curcumin and to evaluate its antitumor activity in vitro. PEG-CUR was prepared by the reaction between curcumin and PEG. PEG-CUR which was characterized by SEM, TEM, FTIR, DSC and 1H NMR analysis. The physicochemical parameters of PEG-CUR such as zeta potential, size distribution, solubility and percentage of curcumin were also investigated. Our results showed that the percentage of curcumin in PEG-CUR was 13.26 ± 1.25 %. PEG-CUR has nanosize values of 96.3 nm and the zeta potential values of - 48.4 mV. The PEG-CUR showed significantly increasing curcumin's solubility in water and another medium such as in 0,1 N HCl, phosphate buffer pH 4.5 and pH 6.8 solution and n-octanol. Our data also have shown cytotoxicity effect of PEG-CUR was much greater than curcumin-free in two different HepG2 and HCT116 cancer cell lines. It could be concluded from our results that the PEG-CUR may be a potential candidate for cancer treatment. Further studies are needed to evaluate the antitumor efficacy of PEG-CUR in vivo.

Analytical investigation for Lorentz forces effect on nanofluid Marangoni boundary layer hydrothermal behavior using HAM

NASA Astrophysics Data System (ADS)

Sheikholeslami, M.; Ganji, D. D.

2017-12-01

In this paper, semi analytical approach is applied to investigate nanofluid Marangoni convection in presence of magnetic field. Koo-Kleinstreuer-Li model is taken into account to simulate nanofluid properties. Homotopy analysis method is utilized to solve the final ordinary equations which are obtained from similarity transformation. Roles of Hartmann number and nanofluid volume fraction are presented graphically. Results show that temperature augments with rise of nanofluid volume fraction. Impact of nanofluid volume fraction on normal velocity is more than tangential velocity. Temperature gradient enhances with rise of magnetic number.

Visualization of the hot chocolate sound effect by spectrograms

NASA Astrophysics Data System (ADS)

Trávníček, Z.; Fedorchenko, A. I.; Pavelka, M.; Hrubý, J.

2012-12-01

We present an experimental and a theoretical analysis of the hot chocolate effect. The sound effect is evaluated using time-frequency signal processing, resulting in a quantitative visualization by spectrograms. This method allows us to capture the whole phenomenon, namely to quantify the dynamics of the rising pitch. A general form of the time dependence volume fraction of the bubbles is proposed. We show that the effect occurs due to the nonlinear dependence of the speed of sound in the gas/liquid mixture on the volume fraction of the bubbles and the nonlinear time dependence of the volume fraction of the bubbles.

Simulation of hydrodynamics using large eddy simulation-second-order moment model in circulating fluidized beds

NASA Astrophysics Data System (ADS)

Juhui, Chen; Yanjia, Tang; Dan, Li; Pengfei, Xu; Huilin, Lu

2013-07-01

Flow behavior of gas and particles is predicted by the large eddy simulation of gas-second order moment of solid model (LES-SOM model) in the simulation of flow behavior in CFB. This study shows that the simulated solid volume fractions along height using a two-dimensional model are in agreement with experiments. The velocity, volume fraction and second-order moments of particles are computed. The second-order moments of clusters are calculated. The solid volume fraction, velocity and second order moments are compared at the three different model constants.

Application of artificial neural networks for the prediction of volume fraction using spectra of gamma rays backscattered by three-phase flows

NASA Astrophysics Data System (ADS)

Gholipour Peyvandi, R.; Islami Rad, S. Z.

2017-12-01

The determination of the volume fraction percentage of the different phases flowing in vessels using transmission gamma rays is a conventional method in petroleum and oil industries. In some cases, with access only to the one side of the vessels, attention was drawn toward backscattered gamma rays as a desirable choice. In this research, the volume fraction percentage was measured precisely in water-gasoil-air three-phase flows by using the backscatter gamma ray technique andthe multilayer perceptron (MLP) neural network. The volume fraction determination in three-phase flows requires two gamma radioactive sources or a dual-energy source (with different energies) while in this study, we used just a 137Cs source (with the single energy) and a NaI detector to analyze backscattered gamma rays. The experimental set-up provides the required data for training and testing the network. Using the presented method, the volume fraction was predicted with a mean relative error percentage less than 6.47%. Also, the root mean square error was calculated as 1.60. The presented set-up is applicable in some industries with limited access. Also, using this technique, the cost, radiation safety and shielding requirements are minimized toward the other proposed methods.

Origins of microstructural transformations in charged vesicle suspensions: the crowding hypothesis.

PubMed

Seth, Mansi; Ramachandran, Arun; Murch, Bruce P; Leal, L Gary

2014-09-02

It is observed that charged unilamellar vesicles in a suspension can spontaneously deflate and subsequently transition to form bilamellar vesicles, even in the absence of externally applied triggers such as salt or temperature gradients. We provide strong evidence that the driving force for this deflation-induced transition is the repulsive electrostatic pressure between charged vesicles in concentrated suspensions, above a critical effective volume fraction. We use volume fraction measurements and cryogenic transmission electron microscopy imaging to quantitatively follow both the macroscopic and microstructural time-evolution of cationic diC18:1 DEEDMAC vesicle suspensions at different surfactant and salt concentrations. A simple model is developed to estimate the extent of deflation of unilamellar vesicles caused by electrostatic interactions with neighboring vesicles. It is determined that when the effective volume fraction of the suspension exceeds a critical value, charged vesicles in a suspension can experience "crowding" due to overlap of their electrical double layers, which can result in deflation and subsequent microstructural transformations to reduce the effective volume fraction of the suspension. Ordinarily in polydisperse colloidal suspensions, particles interacting via a repulsive potential transform into a glassy state above a critical volume fraction. The behavior of charged vesicle suspensions reported in this paper thus represents a new mechanism for the relaxation of repulsive interactions in crowded situations.

Incorporating functionalized polyethylene glycol lipids into reprecipitated conjugated polymer nanoparticles for bioconjugation and targeted labeling of cells

NASA Astrophysics Data System (ADS)

Kandel, Prakash K.; Fernando, Lawrence P.; Ackroyd, P. Christine; Christensen, Kenneth A.

2011-03-01

We report a simple and rapid method to prepare extremely bright, functionalized, stable, and biocompatible conjugated polymer nanoparticles incorporating functionalized polyethylene glycol (PEG) lipids by reprecipitation. These nanoparticles retain the fundamental spectroscopic properties of conjugated polymer nanoparticles prepared without PEG lipid, but demonstrate greater hydrophilicity and quantum yield compared to unmodified conjugated polymer nanoparticles. The sizes of these nanoparticles, as determined by TEM, were 21-26 nm. Notably, these nanoparticles were prepared with several PEG lipid functional end groups, including biotin and carboxy moieties that can be easily conjugated to biomolecules. We have demonstrated the availability of these end groups for functionalization using the interaction of biotin PEG lipid conjugated polymer nanoparticles with streptavidin. Biotinylated PEG lipid conjugated polymer nanoparticles bound streptavidin-linked magnetic beads, while carboxy and methoxy PEG lipid modified nanoparticles did not. Similarly, biotinylated PEG lipid conjugated polymer nanoparticles bound streptavidin-coated glass slides and could be visualized as diffraction-limited spots, while nanoparticles without PEG lipid or with non-biotin PEG lipid end groups were not bound. To demonstrate that nanoparticle functionalization could be used for targeted labelling of specific cellular proteins, biotinylated PEG lipid conjugated polymer nanoparticles were bound to biotinylated anti-CD16/32 antibodies on J774A.1 cell surface receptors, using streptavidin as a linker. This work represents the first demonstration of targeted delivery of conjugated polymer nanoparticles and demonstrates the utility of these new nanoparticles for fluorescence based imaging and sensing.We report a simple and rapid method to prepare extremely bright, functionalized, stable, and biocompatible conjugated polymer nanoparticles incorporating functionalized polyethylene glycol (PEG) lipids by reprecipitation. These nanoparticles retain the fundamental spectroscopic properties of conjugated polymer nanoparticles prepared without PEG lipid, but demonstrate greater hydrophilicity and quantum yield compared to unmodified conjugated polymer nanoparticles. The sizes of these nanoparticles, as determined by TEM, were 21-26 nm. Notably, these nanoparticles were prepared with several PEG lipid functional end groups, including biotin and carboxy moieties that can be easily conjugated to biomolecules. We have demonstrated the availability of these end groups for functionalization using the interaction of biotin PEG lipid conjugated polymer nanoparticles with streptavidin. Biotinylated PEG lipid conjugated polymer nanoparticles bound streptavidin-linked magnetic beads, while carboxy and methoxy PEG lipid modified nanoparticles did not. Similarly, biotinylated PEG lipid conjugated polymer nanoparticles bound streptavidin-coated glass slides and could be visualized as diffraction-limited spots, while nanoparticles without PEG lipid or with non-biotin PEG lipid end groups were not bound. To demonstrate that nanoparticle functionalization could be used for targeted labelling of specific cellular proteins, biotinylated PEG lipid conjugated polymer nanoparticles were bound to biotinylated anti-CD16/32 antibodies on J774A.1 cell surface receptors, using streptavidin as a linker. This work represents the first demonstration of targeted delivery of conjugated polymer nanoparticles and demonstrates the utility of these new nanoparticles for fluorescence based imaging and sensing. Electronic supplementary information (ESI) available: Additional TEM data, supplemental light scattering measurements, absorbance and fluorescence emission spectra, and photostability measurements. See DOI: 10.1039/c0nr00746c

Crystallization of sheared hard spheres at 64.5% volume fraction

NASA Astrophysics Data System (ADS)

Swinney, H. L.; Rietz, F.; Schroeter, M.; Radin, C.

2017-11-01

A classic experiment by G.D. Scott Nature 188, 908, 1960) showed that pouring balls into a rigid container filled the volume to an upper limit of 64% of the container volume, which is well below the 74% volume fraction filled by spheres in a hexagonal close packed (HCP) or face center cubic (FCC) lattice. Subsequent experiments have confirmed a ``random closed packed'' (RCP) fraction of about 64%. However, the physics of the RCP limit has remained a mystery. Our experiment on a cubical box filled with 49400 weakly sheared glass spheres reveals a first order phase transition from a disordered to an ordered state at a volume fraction of 64.5%. The ordered state consists of crystallites of mixed FCC and HCP symmetry that coexist with the amorphous bulk. The transition is initiated by homogeneous nucleation: in the shearing process small crystallites with about ten or fewer spheres dissolve, while larger crystallites grow. A movie illustrates the crystallization process. German Academic Exchange Service (DAAD), German Research Foundation (DFG), NSF DMS, and R.A. Welch Foundation.

Assessment of left atrial volume and function: a comparative study between echocardiography, magnetic resonance imaging and multi slice computed tomography.

PubMed

Kühl, J Tobias; Lønborg, Jacob; Fuchs, Andreas; Andersen, Mads J; Vejlstrup, Niels; Kelbæk, Henning; Engstrøm, Thomas; Møller, Jacob E; Kofoed, Klaus F

2012-06-01

Measurement of left atrial (LA) maximal volume (LA(max)) using two-dimensional transthoracic echocardiography (TTE) provides prognostic information in several cardiac diseases. However, the relationship between LA(max) and LA function is poorly understood and TTE is less well suited for measuring dynamic LA volume changes. Conversely, cardiac magnetic resonance imaging (CMR) and multi-slice computed tomography (MSCT) appears more appropriate for such measures. We sought to determine the relationship between LA size assessed with TTE and LA size and function assessed with CMR and MSCT. Fifty-four patients were examined 3 months post myocardial infarction with echocardiography, CMR and MSCT. Left atrial volumes and LA reservoir function were assessed by TTE. LA time-volume curves were determined and LA reservoir function (cyclic change and fractional change), passive emptying function (reservoir volume) and pump function (left atrial ejection fraction-LAEF) were derived using CMR and MSCT. Left atrial fractional change and left atrial ejection fraction (LAEF) determined with CMR and MSCT were unrelated to LA(max) enlargement by echocardiography (P = NS). There was an overall good agreement between CMR and MSCT, with a small to moderate bias in LA(max) (4.9 ± 10.4 ml), CC (3.1 ± 9.1 ml) and reservoir volume (3.4 ± 9.1 ml). TTE underestimates LA(max) with up to 32% compared with CMR and MSCT (P < 0.001). Left atrial function assessed with MSCT and CMR as LA fractional change and LAEF is not significantly related to LA(max) measured by TTE. TTE systematically underestimated LA volumes, whereas there are good agreements between MSCT and CMR for volumetric and functional properties.

Pancreas volume and fat fraction in children with Type 1 diabetes.

PubMed

Regnell, S E; Peterson, P; Trinh, L; Broberg, P; Leander, P; Lernmark, Å; Månsson, S; Elding Larsson, H

2016-10-01

People with Type 1 diabetes have smaller pancreases than healthy individuals. Several diseases causing pancreatic atrophy are associated with pancreatic steatosis, but pancreatic fat in Type 1 diabetes has not been measured. This cross-sectional study aimed to compare pancreas size and fat fraction in children with Type 1 diabetes and controls. The volume and fat fraction of the pancreases of 22 children with Type 1 diabetes and 29 controls were determined using magnetic resonance imaging. Pancreas volume was 27% smaller in children with diabetes (median 34.9 cm(3) ) than in controls (47.8 cm(3) ; P < 0.001). Pancreas volume correlated positively with age in controls (P = 0.033), but not in children with diabetes (P = 0.649). Pancreas volume did not correlate with diabetes duration, but it did correlate positively with units of insulin/kg body weight/day (P = 0.048). A linear model of pancreas volume as influenced by age, body surface area and insulin units/kg body weight/day found that insulin dosage correlated with pancreas volume after controlling for both age and body surface area (P = 0.009). Pancreatic fat fraction was not significantly different between the two groups (1.34% vs. 1.57%; P = 0.891). Our findings do not indicate that pancreatic atrophy in Type 1 diabetes is associated with an increased pancreatic fat fraction, unlike some other diseases featuring reduced pancreatic volume. We speculate that our results may support the hypotheses that much of pancreatic atrophy in Type 1 diabetes occurs before the clinical onset of the disease and that exogenous insulin administration decelerates pancreatic atrophy after diabetes onset. © 2016 Diabetes UK.

Polyethyleneglycol/silver functionalized reduced graphene oxide aerogel for environmental application

NASA Astrophysics Data System (ADS)

Kumari, G. Vanitha; Asha, S.; Ananth, A. Nimrodh; Rajan, M. A. Jothi; Mathavan, T.

2018-04-01

Polyethylene glycol (PEG)/Silver (Ag) functionalized reduced graphene oxide aerogel (RGOA) was synthesized. PEG/Ag decorated reduced graphene oxide aerogel was characterized using XRD, Raman spectroscopy, Fourier transform infrared spectroscopy (FT-IR). The surface morphology of PEG/Ag/RGOA was analyzed using scanning electron microscope. The non-covalent interaction between reduced graphene oxide layers and the interaction between PEG and Ag on RGOA were studied by FT-IR spectra. It was observed that the interaction between Ag and PEG could enhance the properties of RGOA. Methyl Orange (MO) dye degradation was observed from UV-Vis Spectra. The process was studied by monitoring the simultaneous decrease in the height of UV-Vis absorption peak of dye solution. The results show that PEG/RGOA and PEG/Ag/RGOA are an efficient catalyst for dye degradation.

Cell separation by immunoaffinity partitioning with polyethylene glycol-modified Protein A in aqueous polymer two-phase systems

NASA Technical Reports Server (NTRS)

Karr, Laurel J.; Van Alstine, James M.; Snyder, Robert S.; Shafer, Steven G.; Harris, J. Milton

1988-01-01

Previous work has shown that polyethylene glycol (PEG)-bound antibodies can be used as affinity ligands in PEG-dextran two-phase systems to provide selective partitioning of cells to the PEG-rich phase. In the present work it is shown that immunoaffinity partitioning can be simplified by use of PEG-modified Protein A which complexes with unmodified antibody and cells and shifts their partitioning into the PEG-rich phase, thus eliminating the need to prepare a PEG-modified antibody for each cell type. In addition, the paper provides a more rigorous test of the original technique with PEG-bound antibodies by showing that it is effective at shifting the partitioning of either cell type of a mixture of two cell populations.

Volume fractions of DCE-MRI parameter as early predictor of histologic response in soft tissue sarcoma: A feasibility study.

PubMed

Xia, Wei; Yan, Zhuangzhi; Gao, Xin

2017-10-01

To find early predictors of histologic response in soft tissue sarcoma through volume transfer constant (K trans ) analysis based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). 11 Patients with soft tissue sarcoma of the lower extremity that underwent preoperative chemoradiotherapy followed by limb salvage surgery were included in this retrospective study. For each patient, DCE-MRI data sets were collected before and two weeks after therapy initiation, and histologic tumor cell necrosis rate (TCNR) was reported at surgery. The DCE-MRI volumes were aligned by registration. Then, the aligned volumes were used to obtain the K trans variation map. Accordingly, three sub-volumes (with increased, decreased or unchanged K trans ) were defined and identified, and fractions of the sub-volumes, denoted as F + , F - and F 0 , respectively, were calculated. The predictive ability of volume fractions was determined by using area under a receiver operating characteristic curve (AUC). Linear regression analysis was performed to investigate the relationship between TCNR and volume fractions. In addition, the K trans values of the sub-volumes were compared. The AUC for F - (0.896) and F 0 (0.833) were larger than that for change of tumor longest diameter ΔD (0.625) and the change of mean K trans ΔK trans ¯ (0.792). Moreover, the regression results indicated that TCNR was directly proportional to F 0 (R 2 =0.75, P=0.0003), while it was inversely proportional to F - (R 2 =0.77, P=0.0002). However, TCNR had relatively weak linear relationship with ΔK trans ¯ (R 2 =0.64, P=0.0018). Additionally, TCNR did not have linear relationship with DD (R 2 =0.16, P=0.1246). The volume fraction F - and F 0 have potential as early predictors of soft tissue sarcoma histologic response. Copyright © 2017 Elsevier B.V. All rights reserved.

Can pegylated interferon improve the outcome of polycythemia vera patients?

PubMed

Crisà, Elena; Cerrano, Marco; Beggiato, Eloise; Benevolo, Giulia; Lanzarone, Giuseppe; Manzini, Paola Maria; Borchiellini, Alessandra; Riera, Ludovica; Boccadoro, Mario; Ferrero, Dario

2017-01-13

Pegylated interferon (peg-IFN) was proven by phase II trials to be effective in polycythemia vera (PV); however, it is not clear whether it could improve patient outcome compared to hydroxyurea (HU). Here, we present an observational study on 65 PV patients aged 65 years or younger, who received either peg-IFN (30) or HU (35) according to the physician choice. Median follow-up was 75 months. The two cohorts were comparable for patient and disease characteristics. Eighty-seven percent of the patients treated with peg-INF responded, with a CR rate of 70% as compared to 100 and 49% with HU, respectively. Discontinuation rate was similar in the two groups (20% in peg-IFN vs 17% in HU). JAK2 allele burden was monitored in peg-INF arm only, and a reduction was observed in 88% of the patients. No thrombotic events were observed during peg-IFN treatment compared to three on HU. Disease progression to myelofibrosis or acute myeloid leukemia occurred to a patient only in peg-INF, compared to three in HU. Overall, three second malignancies were observed during the study, two in patients who received HU only, and one in a patient largely treated HU who received also peg-IFN for 3 months. Overall survival was significantly better for peg-IFN patients compared to HU, p = 0.027. Our study, albeit limited by small patient and event number and lack of randomization, confirms the efficacy of peg-INF in PV and shows a significant survival advantage for peg-INF-treated patients. Waiting for confirming data from the ongoing phase III trials, our study can support peg-INF as a first-line treatment option for PV, at least for younger patients.

PNA-PEG modified silicon platforms as functional bio-interfaces for applications in DNA microarrays and biosensors.

PubMed

Cattani-Scholz, Anna; Pedone, Daniel; Blobner, Florian; Abstreiter, Gerhard; Schwartz, Jeffrey; Tornow, Marc; Andruzzi, Luisa

2009-03-09

The synthesis and characterization of two types of silicon-based biofunctional interfaces are reported; each interface bonds a dense layer of poly(ethylene glycol) (PEG(n)) and peptide nucleic acid (PNA) probes. Phosphonate self-assembled monolayers were derivatized with PNA using a maleimido-terminated PEG(45). Similarly, siloxane monolayers were functionalized with PNA using a maleimido-terminated PEG(45) spacer and were subsequently modified with a shorter methoxy-terminated PEG(12) ("back-filling"). The long PEG(45) spacer was used to distance the PNA probe from the surface and to minimize undesirable nonspecific adsorption of DNA analyte. The short PEG(12) "back-filler" was used to provide additional passivation of the surface against nonspecific DNA adsorption. X-ray photoelectron spectroscopic (XPS) analysis near the C 1s and N 1s ionization edges was done to characterize chemical groups formed in the near-surface region, which confirmed binding of PEG and PNA to the phosphonate and silane films. XPS also indicated that additional PEG chains were tethered to the surface during the back-filling process. Fluorescence hybridization experiments were carried out with complementary and noncDNA strands; both phosphonate and siloxane biofunctional surfaces were effective for hybridization of cDNA strands and significantly reduced nonspecific adsorption of the analyte. Spatial patterns were prepared by polydimethylsiloxane (PDMS) micromolding on the PNA-functionalized surfaces; selective hybridization of fluorescently labeled DNA was shown at the PNA functionalized regions, and physisorption at the probe-less PEG-functionalized regions was dramatically reduced. These results show that PNA-PEG derivatized phosphonate monolayers hold promise for the smooth integration of device surface chemistry with semiconductor technology for the fabrication of DNA biosensors. In addition, our results confirm that PNA-PEG derivatized self-assembled carboxyalkylsiloxane films are promising substrates for DNA microarray applications.

[Multifunctional nano-vector for gene delivery into human adipose derived mesenchymal stem cells and in vitro cellular magnetic resonance imaging].

PubMed

Pang, Pengfei; Li, Bing; Hu, Xiaojun; Kang, Zhuang; Guan, Shouhai; Gong, Faming; Meng, Xiaochun; Li, Dan; Huang, Mingsheng; Shan, Hong

2014-04-08

To examine the feasibility and efficacy of using superparamagnetic iron oxide nanoparticles coated with polyethylene glycol-grafted polyethylenimine (PEG-g-PEI-SPION) as a carrier for gene delivery into human adipose derived mesenchymal stem cells (hADMSCs) and in vitro cellular magnetic resonance imaging (MRI). PEG-g-PEI-SPION was synthesized as previously reported. Gel electrophoresis was performed to assess the pDNA condensation capacity of PEG-g-PEI-SPION. The particle size and zeta potential of PEG-g-PEI-SPION/pDNA complexes were determined by dynamic light scattering. Cytotoxicity of PEG-g-PEI-SPION was evaluated by CCK-8 assay with hADMSCs. Gene transfection efficiency of PEG-g-PEI-SPION in hADMSCs was quantified by flow cytometry. The cellular internalization of PEG-g-PEI-SPION/pDNA nanocomplexes was studied by confocal laser scanning microscopy and Prussian blue staining. MRI function of PEG-g-PEI-SPION was studied by in vitro cellular MRI scanning. PEG-g-PEI-SPION condensed pDNA to form stable complexes of 80-100 nm in diameter and showed low cytotoxicity in hADMSCs. At the optimal N/P ratio of 20, PEG-g-PEI-SPION/pDNA obtained the highest transfection efficiency of 22.8% ± 3.6% in hADMSCs. And it was higher than that obtained with lipofectamine 11.2% ± 2.6% (P < 0.05). Furthermore, hADMSCs labeled with PEG-g-PEI-SPION showed sensitive low signal intensity on MRI T2-weighted images in vitro. PEG-g-PEI-SPION is an efficient and MRI-visible nano-vector for gene delivery into hADMSCs.

Development of a novel biocompatible poly(ethylene glycol)-block-poly(γ-cholesterol-L-glutamate) as hydrophobic drug carrier.

PubMed

Ma, Qing; Li, Bo; Yu, Yiyi; Zhang, Ying; Wu, Yang; Ren, Wen; Zheng, Yu; He, Jun; Xie, Yongmei; Song, Xiangrong; He, Gu

2013-03-10

A novel biomaterial poly(ethylene glycol)-block-poly(γ-cholesterol-l-glutamate) (mPEG-PCHLG) was designed and synthesized by introducing cholesterol side chains into this pegylated poly(amino acid) copolymers to enlarge the core space to increase the drug capacity. Paclitaxel (PTX) loaded mPEG-PCHLG nanoparticles (PTX-mPEG-PCHLG-Nps) were developed for the first time. The preparation method of nanoparticles was screened and optimized systemically. The optimal PTX-mPEG-PCHLG-Nps with the average diameter of 213.71 nm were constructed through the O/W single-emulsion solvent evaporation method. The entrapment efficiency and drug loading was 38.02 ± 4.51% and 93.90 ± 4.56%, respectively. PTX-mPEG-PCHLG-Nps were spherical and well-dispersed and displayed a dramatic sustained-release property. The in vitro cytotoxicity experiments demonstrated that the blank mPEG-PCHLG nanoparticles had no cytotoxicities on four tumor cell lines including A549, HepG-2, MCF-7 and C26, which implied that mPEG-PCHLG might be biocompatible. PTX-mPEG-PCHLG-Nps obtained the same cell growth inhibition activities as free PTX when incubated with the above tumor cells for 48h. It can be inferred that PTX-mPEG-PCHLG-Nps could probably have higher anticancer efficacy due to the inadequate release of PTX from nanoparticles. PTX-mPEG-PCHLG-Nps achieved the highest antitumor activity in A549 rather than HepG-2, MCF-7 and C26, thus PTX-mPEG-PCHLG-Nps could have a potential application in lung cancer therapy. All the data indicated that mPEG-PCHLG was one of biocompatible biomaterials and worth being widely investigated as hydrophobic antitumor drug carrier. Copyright © 2013 Elsevier B.V. All rights reserved.

Randomized clinical trial: macrogol/PEG 3350 plus electrolytes for treatment of patients with constipation associated with irritable bowel syndrome.

PubMed

Chapman, R W; Stanghellini, V; Geraint, M; Halphen, M

2013-09-01

Polyethylene glycol (PEG) 3350 plus electrolytes (PEG 3350+E) is an established treatment for constipation and has been proposed as a treatment option for constipation associated with irritable bowel syndrome (IBS-C). This study aimed to compare the efficacy and safety of PEG 3350+E vs. placebo in adult patients with IBS-C. Following a 14-day run-in period without study medication, patients with confirmed IBS-C were randomized to receive PEG 3350+E (N=68) or placebo (N=71) for 28 days. The primary endpoint was the mean number of spontaneous bowel movements (SBMs) per day in the last treatment week. In both groups, mean weekly number of SBMs (±s.d.) increased from run-in. The difference between the groups in week 4 (PEG 3350+E, 4.40±2.581; placebo, 3.11±1.937) was statistically significant (95% confidence interval: 1.17, 1.95; P<0.0001). Although mean severity score for abdominal discomfort/pain was significantly reduced compared with run-in with PEG 3350+E, there was no difference vs. placebo. Spontaneous complete bowel movements, responder rates, stool consistency, and severity of straining also showed superior improvement in the PEG 3350+E group over placebo in week 4. The most common drug related treatment-emergent adverse events were abdominal pain (PEG 3350+E, 4.5%; placebo, 0%) and diarrhoea (PEG 3350+E, 4.5%; placebo, 4.3%). In IBS-C, PEG 3350+E was superior to placebo for relief of constipation, and although a statistically significant improvement in abdominal discomfort/pain was observed compared with baseline, there was no associated improvement compared with placebo. PEG 3350+E is a well-established and effective treatment that should be considered suitable for use in IBS-C.

Effects of PEG tethering chain length of vitamin E TPGS with a Herceptin-functionalized nanoparticle formulation for targeted delivery of anticancer drugs.

PubMed

Zhao, Jing; Feng, Si-Shen

2014-03-01

Drug formulation by ligand conjugated nanoparticles of biodegradable polymers has become one of the most important strategies in drug targeting. We have developed in our previous work nanoparticles of a mixture of two vitamin E TPGS based copolymers PLA-TPGS and TPGS-TOOH with the latter for Herceptin conjugation for targeted delivery of anticancer drugs such as docetaxel to the cancer cells of human epidermal growth factor receptor 2 (HER2) overexpression. In this research, we investigated the effects of the PEG chain length in TPGS, which is in fact a PEGylated vitamin E, on the cellular uptake and cytotoxicity of the drug formulated in the Herceptin-conjugated nanoparticles of PLA-TPGS/TPGS-COOH blend (NPs). Such NPs of PEG1000, PEG2000, PEG3350 and PEG5000, i.e. the PEG of molecule weight 1000, 2000, 3350 and 5000, were prepared by the nanoprecipitation method and characterized for their size and size distribution, drug loading, surface morphology, surface charge and surface chemistry as well as in vitro drug release profile, cellular uptake and cytotoxicity. We found among such nanoparticles, those of PEG1000, i.e. of the shortest PEG tethering chain length, could result in the best therapeutic effects, which are 24.1%, 37.3%, 38.1% more efficient in cellular uptake and 68.1%, 90%, 92.6% lower in IC50 (thus higher in cytotoxicity) than the Herceptin-conjugated nanoparticles of PLA-TPGS/TPGS-COOH blend of PEG2000, PEG3350 and PEG5000 respectively in treatment of SK-BR-3 cancer cells which are of high HER2 overexpression. We provided a theoretical explanation from surface mechanics and thermodynamics for endocytosis of nanoparticles. Copyright © 2014 Elsevier Ltd. All rights reserved.

A safe and efficient hepatocyte-selective carrier system based on myristoylated preS1/21-47 domain of hepatitis B virus

NASA Astrophysics Data System (ADS)

Zhang, Quan; Zhang, Xuanmiao; Chen, Tijia; Wang, Xinyi; Fu, Yao; Jin, Yun; Sun, Xun; Gong, Tao; Zhang, Zhirong

2015-05-01

A safe and efficient liver targeted PEGylated liposome (PEG-Lip) based on N-terminal myristoylated preS1/21-47 (preS1/21-47myr) of hepatitis B virus was successfully developed. The study aimed to elucidate the cellular uptake mechanism of preS1/21-47myr modified PEG-Lip (preS1/21-47myr-PEG-Lip) in hepatogenic cells and the distribution behavior of preS1/21-47myr-PEG-Lip in Vr:CD1 (ICR) mice. The cellular uptake results showed that preS1/21-47myr-PEG-Lip was effectively taken up by hepatogenic cells (including primary hepatocytes and liver tumor cells) through a receptor-mediated endocytosis pathway compared with non-hepatogenic cells. After systemic administration to H22 hepatoma-bearing mice, preS1/21-47myr-PEG-Lip showed significant liver-specific delivery and an increase in the distribution of preS1/21-47myr-PEG-Lip in hepatic tumor. Furthermore, the antitumor effect of preS1/21-47myr-PEG-Lip loaded with paclitaxel (PTX) was remarkably stronger than that of PTX injection and PTX loaded liposomes (including common liposomes and PEG-Lip). In safety evaluation, no acute systemic toxicity and immunotoxicity were observed after intravenous injection of preS1/21-47myr-PEG-Lip. No liver toxicity was observed despite the dramatic increase of preS1/21-47myr-PEG-Lip in liver. Taken together, preS1/21-47myr-PEG-Lip represents a promising carrier system for targeted liver disease therapy and imaging.

Construction and characterization of Gal-chitosan graft methoxy poly (ethylene glycol) (Gal-CS-mPEG) nanoparticles as efficient gene carrier

NASA Astrophysics Data System (ADS)

Jin, Jiting; Fu, Wandong; Liao, Miaofei; Han, Baoqin; Chang, Jing; Yang, Yan

2017-10-01

In the present study, galactosylated chitosan (Gal-CS) was conjugated with methoxy poly(ethylene glycol) (mPEG) as a hydrophilic group. The structure of Gal-CS-mPEG polymer was characterized and the nanoparticles (NPs) were prepared using ironic gelation method. The study was designed to investigate the characteristics and functions of Gal-CS-mPEG NPs. The morphology of Gal-CS-mPEG NPs was observed by SEM and it was a compact and spherical shape. The size of the NPs was approximately 200 nm in diameter under the ideal process parameters. The interaction between Gal-CS-mPEG NPs and pDNA, and the protection of pDNA against DNase I and serum degradation by Gal-CS-mPEG NPs were evaluated. Agarose gel electrophoresis results showed that Gal-CS-mPEG NPs had strong interaction with pDNA at the weight ratio of 12:1, 4:1 and 2:1 and could protect pDNA from DNase I and serum degradation. Gal-CS-mPEG NPs exhibited high loading efficiency and sustainable in vitro release. The blood compatibility studies demonstrated that Gal-CS-mPEG NPs had superior compatibility with erythrocytes in terms of aggregation degree and hemolysis level. Gal-CS-mPEG NPs showed no cytotoxicity on L929 cells, which is a normal mouse connective tissue fibroblast, but showed inhibitory effects on the proliferation of Bel-7402 cells, which is a liver cancer cell line. In conclusion, Gal-CS-mPEG NP is a bio-safe and efficient gene carrier with potential application in gene delivery.

Solid freeform fabrication and in-vitro response of osteoblast cells of mPEG-PCL-mPEG bone scaffolds.

PubMed

Jiang, Cho-Pei; Chen, Yo-Yu; Hsieh, Ming-Fa; Lee, Hung-Maan

2013-04-01

Bone tissue engineering is an emerging approach to provide viable substitutes for bone regeneration. Poly(ethylene glycol) (PEG) is a good candidate of bone scaffold because of several advantages such as hydrophilicity, biocompatibility, and intrinsic resistance to protein adsorption and cell adhesion. However, its low compressive strength limits application for bone regeneration. Poly(ε-caprolactone) (PCL), a hydrophobic nonionic polymer, is adopted to enhance the compressive strength of PEG alone.We aimed to investigate the in-vitro response of osteoblast-like cells cultured with porous scaffolds of triblock PEG-PCL-PEG copolymer fabricated by an air pressure-aided deposition system. A desktop air pressure-aided deposition system that involves melting and plotting PEG-PCL-PEG was used to fabricate three-dimensional scaffolds having rectangular pores. The experimental results showed that PEG-PCL-PEG with a molecular weight of 25,000 can be melted and stably deposited through a heating nozzle at an air pressure of 0.3 MPa and no crack occurs after it solidifies. The scaffolds with pre-determined pore size of 400× 420 μm and a porosity of 79 % were fabricated, and their average compressive strength was found to be 18.2 MPa. Osteoblast-like cells, MC3T3-E1, were seeded on fabricated scaffolds to investigate the in-vitro response of cells including toxicity and cellular locomotion. In a culture period of 28 days, the neutral-red stained osteoblasts were found to well distributed in the interior of the scaffold. Furthermore, the cellular attachment and movement in the first 10 h of cell culture were observed with time-lapse microscopy indicating that the porous PEG-PCL-PEG scaffolds fabricated by air pressure-aided deposition system is non-toxicity for osteoblast-like cells.

Brown Adipose Tissue Quantification in Human Neonates Using Water-Fat Separated MRI

PubMed Central

Rasmussen, Jerod M.; Entringer, Sonja; Nguyen, Annie; van Erp, Theo G. M.; Guijarro, Ana; Oveisi, Fariba; Swanson, James M.; Piomelli, Daniele; Wadhwa, Pathik D.

2013-01-01

There is a major resurgence of interest in brown adipose tissue (BAT) biology, particularly regarding its determinants and consequences in newborns and infants. Reliable methods for non-invasive BAT measurement in human infants have yet to be demonstrated. The current study first validates methods for quantitative BAT imaging of rodents post mortem followed by BAT excision and re-imaging of excised tissues. Identical methods are then employed in a cohort of in vivo infants to establish the reliability of these measures and provide normative statistics for BAT depot volume and fat fraction. Using multi-echo water-fat MRI, fat- and water-based images of rodents and neonates were acquired and ratios of fat to the combined signal from fat and water (fat signal fraction) were calculated. Neonatal scans (n = 22) were acquired during natural sleep to quantify BAT and WAT deposits for depot volume and fat fraction. Acquisition repeatability was assessed based on multiple scans from the same neonate. Intra- and inter-rater measures of reliability in regional BAT depot volume and fat fraction quantification were determined based on multiple segmentations by two raters. Rodent BAT was characterized as having significantly higher water content than WAT in both in situ as well as ex vivo imaging assessments. Human neonate deposits indicative of bilateral BAT in spinal, supraclavicular and axillary regions were observed. Pairwise, WAT fat fraction was significantly greater than BAT fat fraction throughout the sample (ΔWAT-BAT = 38%, p<10−4). Repeated scans demonstrated a high voxelwise correlation for fat fraction (Rall = 0.99). BAT depot volume and fat fraction measurements showed high intra-rater (ICCBAT,VOL = 0.93, ICCBAT,FF = 0.93) and inter-rater reliability (ICCBAT,VOL = 0.86, ICCBAT,FF = 0.93). This study demonstrates the reliability of using multi-echo water-fat MRI in human neonates for quantification throughout the torso of BAT depot volume and fat fraction measurements. PMID:24205024

Spontaneous transfer of stearic acids between human serum albumin and PEG:2000-grafted DPPC membranes.

PubMed

Pantusa, Manuela; Stirpe, Andrea; Sportelli, Luigi; Bartucci, Rosa

2010-05-01

Electron spin resonance (ESR) spectroscopy is used to study the transfer of stearic acids between human serum albumin (HSA) and sterically stabilized liposomes (SSL) composed of dipalmitoylphosphatidylcholine (DPPC) and of submicellar content of poly(ethylene glycol:2000)-dipalmitoylphosphatidylethanolamine (PEG:2000-DPPE). Protein/lipid dispersions are considered in which spin-labelled stearic acids at the 16th carbon atom along the acyl chain (16-SASL) are inserted either in the protein or in the SSL. Two component ESR spectra with different rotational mobility are obtained over a broad range of temperature and membrane composition. Indeed, superimposed to an anisotropic protein-signal, appears a more isotropic lipid-signal. Since in the samples only one matrix (protein or membranes) is spin-labelled, the other component accounts for the transfer of 16-SASL between albumin and membranes. The two components have been resolved and quantified by spectral subtractions, and the fraction, f (p) (16-SASL), of spin labels bound non-covalently to the protein has been used to monitor the transfer. It is found that it depends on the type of donor and acceptor matrix, on the physical state of the membranes and on the grafting density of the polymer-lipids. Indeed, it is favoured from SSL to HSA and the fraction of stearic acids transferred increases with temperature in both directions of transfer. Moreover, in the presence of polymer-lipids, the transfer from HSA to SSL is slightly attenuated, especially in the brush regime of the polymer-chains. Instead, the transfer from SSL to HSA is favoured by the polymer-lipids much more in the mushroom than in the brush regime.

New process for purifying high purity α1-antitrypsin from Cohn Fraction IV by chromatography: A promising method for the better utilization of plasma.

PubMed

Huangfu, Chaoji; Zhang, Jinchao; Ma, Yuyuan; Jia, Junting; Lv, Maomin; Zhao, Xiong; Zhang, Jingang

2017-03-01

α1-antitrypsin (AAT) is a 52kDa serine protease inhibitor that is abundant in plasma. It is synthesized mainly by hepatic cells, and widely used to treat patients with emphysema due to congenital deficiency of AAT. A new isolation method for the purification of AAT from Cohn Fraction IV (Cohn F IV) is described. Cohn F IV is usually discarded as a byproduct from Cohn process. Using Cohn F IV as starting material does not interfere with the production of other plasma proteins and the cost of purification could be reduced greatly. Parameters of each step during purification were optimized, 15% polyethyleneglycol (PEG) concentration and pH 5.2 for PEG precipitation, elution with 0.05M sodium acetate and pH 4.7 for ion-exchange chromatography, and two steps blue sepharose affinity chromatography were chosen for AAT purification. The final protein with purity of 98.17%, specific activity of 3893.29 IU/mg, and yield of 28.35%, was achieved. Western blotting was applied for qualitative identification of final product, which specifically reacted with goat anti-human AAT antibody. LC-ESI-MS/MS was also employed to confirm the final protein. High performance liquid chromatography was used to analyze the composition of purified protein suggesting that pure protein was achieved. The molecular weight of AAT is 51062.77Da which was identified by LC-MS-MS. The manufacturing process described here may make better use of human plasma with Cohn F IV as starting material. The simple process described in this study is simple and inexpensive, it has a potential value for large scale production. Copyright © 2017 Elsevier B.V. All rights reserved.

Heat treatment of normal human sera reveals antibodies to bactericidal permeability-inducing protein (BPI)

PubMed Central

BROWNLEE, AA; LOCKWOOD, CM

1999-01-01

Heat treatment of normal sera to 56°C for 30 min, a common procedure for the inactivation of viruses, e.g. HIV, reveals the presence of antibodies to neutrophil cytoplasm antigens (ANCA), as detected by indirect immunofluorescence on ethanol-fixed human neutrophils and by antigen-specific ELISA for BPI. Reactivity was not seen to the other common vasculitis-associated antigens proteinase 3 (PR3) or myeloperoxidase (MPO). The effect of temperature was maximal at 56°C, with substantial antibody demonstrable after only 5 min at this temperature. In experiments using polyethylene glycol (PEG)6000 to remove immune complexes, the effect of heating could be abrogated by preincubation with 8% PEG, which suggested that these anti BPI antibodies might be complexed in sera. After passage of normal plasma over a protein G column, the acid-eluted fraction contained elevated levels of antibodies to BPI but not to other vasculitis-associated antigens such as PR3 or MPO, nor to glomerular basement membrane (GBM), the Goodpasture antigen which is recognized by the pathogenically important human antibodies shown to mediate nephritis in transfer experiments. Moreover the levels of anti-BPI in the IgG fraction could be augmented by preincubation with glycine pH 2.5 for 30 min. This anti-BPI activity could be inhibited by addition of the unbound material from the protein G column and this inhibitory material was not heat-labile at 56°C. The molecular specificity of this autoreactivity was confirmed using recombinant BPI in coincubation experiments and the epitope localized to the C or N terminal moieties by the use of recombinant fusion proteins. PMID:10403934

Interaction of poly(ethylene-glycols) with air-water interfaces and lipid monolayers: investigations on surface pressure and surface potential.

PubMed Central

Winterhalter, M; Bürner, H; Marzinka, S; Benz, R; Kasianowicz, J J

1995-01-01

We have characterized the surface activity of different-sized poly(ethylene-glycols) (PEG; M(r) 200-100,000 Da) in the presence or absence of lipid monolayers and over a wide range of bulk PEG concentrations (10(-8)-10% w/v). Measurements of the surface potential and surface pressure demonstrate that PEGs interact with the air-water and lipid-water interfaces. Without lipid, PEG added either to the subphase or to the air-water interface forms relatively stable monolayers. Except for very low molecular weight polymers (PEGs < 1000 Da), low concentrations of PEG in the subphase (between 10(-5) and 10(-4)% w/v) increase the surface potential from zero (with respect to the potential of a pure air-water interface) to a plateau value of approximately 440 mV. At much higher polymer concentrations, > 10(-1)% (w/v), depending on the molecular weight of the PEG and corresponding to the concentration at which the polymers in solution are likely to overlap, the surface potential decreases. High concentrations of PEG in the subphase cause a similar decrease in the surface potential of densely packed lipid monolayers spread from either diphytanoyl phosphatidylcholine (DPhPC), dipalmitoyl phosphatidylcholine (DPPC), or dioleoyl phosphatidylserine (DOPS). Adding PEG as a monolayer at the air-water interface also affects the surface activity of DPhPC or DPPC monolayers. At low lipid concentration, the surface pressure and potential are determined by the polymer. For intermediate lipid concentrations, the surface pressure-area and surface potential-area isotherms show that the effects due to lipid and PEG are not always additive and that the polymer's effect is distinct for the two lipids. When PEG-lipid-mixed monolayers are compressed to surface pressures greater than the collapse pressure for a PEG monolayer, the surface pressure-area and surface potential-area isotherms approach that of the lipid alone, suggesting that for this experimental condition PEG is expelled from the interface. PMID:8534807

Pharmacokinetic analysis of multi PEG-theophylline conjugates.

PubMed

Grassi, Mario; Bonora, Gian Maria; Drioli, Sara; Cateni, Francesca; Zacchigna, Marina

2012-10-01

In the attempt of prolonging the effect of drugs, a new branched, high-molecular weight multimeric poly(ethylene glycol) (MultiPEG), synthesized with a simple assembling procedure that devised the introduction of functional groups with divergent and selective reactivity, was employed as drug carrier. In particular, the attention was focused on the study of theophylline (THEO) and THEO-MultiPEG conjugates pharmacokinetic after oral administration in rabbit. Pharmacokinetic behavior was studied according to an ad hoc developed mathematical model accounting for THEO-MultiPEG in vivo absorption and decomposition into drug (THEO) and carrier (MultiPEG). The branched high-molecular weight MultiPEG proved to be a reliable drug delivery system able to prolong theophylline staying in the blood after oral administration of a THEO-MultiPEG solution. The analysis of experimental data by means of the developed mathematical model revealed that the prolongation of THEO effect was essentially due to the low THEO-MultiPEG permeability in comparison to that of pure THEO. Copyright © 2012 Elsevier Ltd. All rights reserved.

Informed peg-in-hole insertion using optical sensors

NASA Astrophysics Data System (ADS)

Paulos, Eric; Canny, John F.

1993-08-01

Peg-in-hole insertion is not only a longstanding problem in robotics but the most common automated mechanical assembly task. In this paper we present a high precision, self-calibrating peg-in-hole insertion strategy using several very simple, inexpensive, and accurate optical sensors. The self-calibrating feature allows us to achieve successful dead-reckoning insertions with tolerances of 25 microns without any accurate initial position information for the robot, pegs, or holes. The program we implemented works for any cylindrical peg, and the sensing steps do not depend on the peg diameter, which the program does not know. The key to the strategy is the use of a fixed sensor to localize both a mobile sensor and the peg, while the mobile sensor localizes the hole. Our strategy is extremely fast, localizing pegs as they are in route to their insertion location without pausing. The result is that insertion times are dominated by the transport time between pick and place operations.

Separation and quantitation of polyethylene glycols 400 and 3350 from human urine by high-performance liquid chromatography.

PubMed

Ryan, C M; Yarmush, M L; Tompkins, R G

1992-04-01

Polyethylene glycol 3350 (PEG 3350) is useful as an orally administered probe to measure in vivo intestinal permeability to macromolecules. Previous methods to detect polyethylene glycol (PEG) excreted in the urine have been hampered by inherent inaccuracies associated with liquid-liquid extraction and turbidimetric analysis. For accurate quantitation by previous methods, radioactive labels were required. This paper describes a method to separate and quantitate PEG 3350 and PEG 400 in human urine that is independent of radioactive labels and is accurate in clinical practice. The method uses sized regenerated cellulose membranes and mixed ion-exchange resin for sample preparation and high-performance liquid chromatography with refractive index detection for analysis. The 24-h excretion for normal individuals after an oral dose of 40 g of PEG 3350 and 5 g of PEG 400 was 0.12 +/- 0.04% of the original dose of PEG 3350 and 26.3 +/- 5.1% of the original dose of PEG 400.

An Experimental Investigation of the Laminar Flamelet Concept for Soot Properties

NASA Technical Reports Server (NTRS)

Diez, F. J.; Aalburg, C.; Sunderland, P. B.; Urban, D. L.; Yuan, Z.-G.; Faeth, G. M.

2007-01-01

The soot properties of round, nonbuoyant, laminar jet diffusion flames are described, based on experiments at microgravity carried out on orbit during three flights of the Space Shuttle Columbia, (Flights STS-83, 94 and 107). Experimental conditions included ethylene- and propane-fueled flames burning in still air at an ambient temperature of 300 K and ambient pressures of 35-100 kPa. Measurements included soot volume fraction distributions using deconvoluted laser extinction imaging, and soot temperature distributions using deconvoluted multiline emission imaging. Flowfield modeling based on the work of Spalding is presented. The present work explores whether soot properties of these flames are universal functions of mixture fraction, i.e., whether they satisfy soot state relationships. Measurements are presented, including radiative emissions and distributions of soot temperature and soot volume fraction. It is shown that most of the volume of these flames is bounded by the dividing streamline and thus should follow residence time state relationships. Most streamlines from the fuel supply to the surroundings are found to exhibit nearly the same maximum soot volume fraction and temperature. The radiation intensity along internal streamlines also is found to have relatively uniform values. Finally, soot state relationships were observed, i.e., soot volume fraction was found to correlate with estimated mixture fraction for each fuel/pressure selection. These results support the existence of soot property state relationships for steady nonbuoyant laminar diffusion flames, and thus in a large class of practical turbulent diffusion flames through the application of the laminar flamelet concept.

Experimental and theoretical investigation of thermal conductivity of ethylene glycol containing functionalized single walled carbon nanotubes

NASA Astrophysics Data System (ADS)

Hemmat Esfe, Mohammad; Firouzi, Masoumeh; Afrand, Masoud

2018-01-01

In this paper, functionalized single walled carbon nanotubes (FSWCNTs) were suspended in Ethylene Glycol (EG) at different volume fractions. A KD2 pro thermal conductivity meter was used to measure the thermal conductivity in the temperature range from 30 to 50 °C. Nanofluids were prepared in solid volume fraction of 0.02, 0.05, 0.075, 0.1, 0.25, 0.5 and, 0.75%. Experimental results revealed that the thermal conductivity of the nanofluid is a non-linear function of temperature and SWCNTs volume fraction in the range of this investigation. Thermal conductivity increases with temperature and nanoparticles volume fraction as usual for this type of nanofluid. Maximum increment in thermal conductivity of the nanofluids was found to be about 45% at 0.75 vol fractions loading at 50 °C. Finally, a new correlation based on artificial neural network (ANN) approach has been proposed for SWCNT-EG thermal conductivity in terms of nanoparticles volume fraction and temperature using the experimental data. Used ANN approach has estimated the experimental values of thermal conductivity with the absolute average relative deviation lower than 0.9%, mean square error of 3.67 × 10-5 and regression coefficient of 0.9989. Comparison between the suggested techniques with various used correlation in the literatures established that the ANN approach is better to other presented methods and therefore can be proposed as a useful means for predicting of the nanofluids thermal conductivity.

Alleviation of Osmotic Stress Effects by Exogenous Application of Salicylic or Abscisic Acid on Wheat Seedlings

PubMed Central

Marcińska, Izabela; Czyczyło-Mysza, Ilona; Skrzypek, Edyta; Grzesiak, Maciej T.; Janowiak, Franciszek; Filek, Maria; Dziurka, Michał; Dziurka, Kinga; Waligórski, Piotr; Juzoń, Katarzyna; Cyganek, Katarzyna; Grzesiak, Stanisław

2013-01-01

The aim of the study was to assess the role of salicylic acid (SA) and abscisic acid (ABA) in osmotic stress tolerance of wheat seedlings. This was accomplished by determining the impact of the acids applied exogenously on seedlings grown under osmotic stress in hydroponics. The investigation was unique in its comprehensiveness, examining changes under osmotic stress and other conditions, and testing a number of parameters simultaneously. In both drought susceptible (SQ1) and drought resistant (CS) wheat cultivars, significant physiological and biochemical changes were observed upon the addition of SA (0.05 mM) or ABA (0.1 μM) to solutions containing half-strength Hoagland medium and PEG 6000 (−0.75 MPa). The most noticeable result of supplementing SA or ABA to the medium (PEG + SA and PEG + ABA) was a decrease in the length of leaves and roots in both cultivars. While PEG treatment reduced gas exchange parameters, chlorophyll content in CS, and osmotic potential, and conversely, increased lipid peroxidation, soluble carbohydrates in SQ1, proline content in both cultivars and total antioxidants activity in SQ1, PEG + SA or PEG + ABA did not change the values of these parameters. Furthermore, PEG caused a two-fold increase of endogenous ABA content in SQ1 and a four-fold increase in CS. PEG + ABA increased endogenous ABA only in SQ1, whereas PEG + SA caused a greater increase of ABA content in both cultivars compared to PEG. In PEG-treated plants growing until the harvest, a greater decrease of yield components was observed in SQ1 than in CS. PEG + SA, and particularly PEG + ABA, caused a greater increase of these yield parameters in CS compared to SQ1. In conclusion, SA and ABA ameliorate, particularly in the tolerant wheat cultivar, the harmful effects and after effects of osmotic stress induced by PEG in hydroponics through better osmotic adjustment achieved by an increase in proline and carbohydrate content as well as by an increase in antioxidant activity. PMID:23803653

Inhibition mechanism of P-glycoprotein mediated efflux by mPEG-PLA and influence of PLA chain length on P-glycoprotein inhibition activity.

PubMed

Li, Wenjing; Li, Xinru; Gao, Yajie; Zhou, Yanxia; Ma, Shujin; Zhao, Yong; Li, Jinwen; Liu, Yan; Wang, Xinglin; Yin, Dongdong

2014-01-06

The present study aimed to investigate the effect of monomethoxy poly(ethylene glycol)-block-poly(D,L-lactic acid) (mPEG-PLA) on the activity of P-glycoprotein (P-gp) in Caco-2 cells and further unravel the relationship between PLA chain length in mPEG-PLA and influence on P-gp efflux and the action mechanism. The transport results of rhodamine 123 (R123) across Caco-2 cell monolayers suggested that mPEG-PLA unimers were responsible for its P-gp inhibitory effect. Furthermore, transport studies of R123 revealed that the inhibitory potential of P-gp efflux by mPEG-PLA analogues was strongly correlated with their structural features and showed that the hydrophilic mPEG-PLA copolymers with an intermediate PLA chain length and 10.20 of hydrophilic-lipophilic balance were more effective at inhibiting P-gp efflux in Caco-2 cells. The fluorescence polarization measurement results ruled out the plasma membrane fluidization as a contributor for inhibition of P-gp by mPEG-PLA. Concurrently, mPEG-PLA inhibited neither basal P-gp ATPase (ATP is adenosine triphosphate) activity nor substrate stimulated P-gp ATPase activity, suggesting that mPEG-PLA seemed not to be a substrate of P-gp and a competitive inhibitor. No evident alteration in P-gp surface level was detected by flow cytometry upon exposure of the cells to mPEG-PLA. The depletion of intracellular ATP, which was likely to be a result of partial inhibition of cellular metabolism, was directly correlated with inhibitory potential for P-gp mediated efflux by mPEG-PLA analogues. Hence, intracellular ATP-depletion appeared to be possible explanation to the inhibition mechanism of P-gp by mPEG-PLA. Taken together, the establishment of a relationship between PLA chain length and impact on P-gp efflux activity and interpretation of action mechanism of mPEG-PLA on P-gp are of fundamental importance and will facilitate future development of mPEG-PLA in the drug delivery area.

Solubility determination of raloxifene hydrochloride in ten pure solvents at various temperatures: Thermodynamics-based analysis and solute-solvent interactions.

PubMed

Ahad, Abdul; Shakeel, Faiyaz; Alfaifi, Omar Ali; Raish, Mohammad; Ahmad, Ajaz; Al-Jenoobi, Fahad I; Al-Mohizea, Abdullah M

2018-06-10

The purpose of the present study was to determine the solubility of raloxifene hydrochloride (RHCl) in ten solvents: water, ethanol, isopropyl alcohol (IPA), ethylene glycol (EG), propylene glycol (PG), polyethylene glycol-400 (PEG-400), Transcutol, 1-butanol, dimethyl sulfoxide (DMSO), and ethyl acetate (EA) at temperatures of 298.2-323.2 K and a pressure of 0.1 MPa. The solubility data obtained was fitted upon "Apelblat and Van't Hoff" equations. The maximum mole fraction solubility of RHCl was obtained in DMSO (5.02 × 10 -2 at 323.2 K), followed by PEG-400 (5.92 × 10 -3 at 323.2 K), EA (3.11 × 10 -3 at 323.2 K), Transcutol (1.22 × 10 -3 at 323.2 K), PG (2.19 × 10 -4 at 323.2 K), 1-butanol (1.96 × 10 -4 at 323.2 K), IPA (1.47 × 10 -4 at 323.2 K), ethanol (7.90 × 10 -5 at 323.2 K), EG (6.65 × 10 -5 at 323.2 K), and water (3.60 × 10 -5 at 323.2 K). Similar fashions were noticed at each studied temperature. The higher solubility of RHCl in DMSO, PEG-400, EA, and Transcutol was possibly referable to their lower polarity in comparison with water. The molecular interactions between the solute and solvent molecules were estimated by calculating parameters like activity coefficients, and more prominent solute-solvent molecular interactions were noted for RHCl-DMSO, RHCl-EA, and RHCl-PEG-400 in comparison with the other solute-solvent combinations. The outcomes of the "apparent thermodynamic analysis" showed that the dissolution of RHCl was "endothermic, spontaneous and entropy-driven" in all investigated solvents. The obtained solubility data of RHCl in commonly used solvents could be useful in the purification, recrystallization, and dosage form design of the drug. Copyright © 2018 Elsevier B.V. All rights reserved.

An Experimental Investigation of Potential Icing of the Space Shuttle External Tank,

DTIC Science & Technology

1982-09-01

PEG 4000, a PEG 1000/400 mixture, and PEG 6000. The number corresponds to the molecular weight of the compound. 2 4.65m Foam Inslation Side 8 ob o 4m(l...Level Emiseivity panel (PEG coated) (Uncoated) Emissivity Panel Left Right 1 4.4 -28.8 -31.6 4.7 -12.2 -15.3 2 4.4 -20.2 -22.2 4.7 -12.8 -13.4 3 4.3...constant dry bulb temperature of 60*F. PEG was tested on one half of side A of the panel. A mixture of 450 g of molecular weight 4000 PEG and 400 g of H20

Abnormal brain white matter microstructure is associated with both pre-hypertension and hypertension

PubMed Central

Gao, He; Bai, Wenjia; Evangelou, Evangelos; Glocker, Ben; O’Regan, Declan P.; Elliott, Paul; Matthews, Paul M.

2017-01-01

Objectives To characterize effects of chronically elevated blood pressure on the brain, we tested for brain white matter microstructural differences associated with normotension, pre-hypertension and hypertension in recently available brain magnetic resonance imaging data from 4659 participants without known neurological or psychiatric disease (62.3±7.4 yrs, 47.0% male) in UK Biobank. Methods For assessment of white matter microstructure, we used measures derived from neurite orientation dispersion and density imaging (NODDI) including the intracellular volume fraction (an estimate of neurite density) and isotropic volume fraction (an index of the relative extra-cellular water diffusion). To estimate differences associated specifically with blood pressure, we applied propensity score matching based on age, sex, educational level, body mass index, and history of smoking, diabetes mellitus and cardiovascular disease to perform separate contrasts of non-hypertensive (normotensive or pre-hypertensive, N = 2332) and hypertensive (N = 2337) individuals and of normotensive (N = 741) and pre-hypertensive (N = 1581) individuals (p<0.05 after Bonferroni correction). Results The brain white matter intracellular volume fraction was significantly lower, and isotropic volume fraction was higher in hypertensive relative to non-hypertensive individuals (N = 1559, each). The white matter isotropic volume fraction also was higher in pre-hypertensive than in normotensive individuals (N = 694, each) in the right superior longitudinal fasciculus and the right superior thalamic radiation, where the lower intracellular volume fraction was observed in the hypertensives relative to the non-hypertensive group. Significance Pathological processes associated with chronically elevated blood pressure are associated with imaging differences suggesting chronic alterations of white matter axonal structure that may affect cognitive functions even with pre-hypertension. PMID:29145428

Accelerated Gray and White Matter Deterioration With Age in Schizophrenia.

PubMed

Cropley, Vanessa L; Klauser, Paul; Lenroot, Rhoshel K; Bruggemann, Jason; Sundram, Suresh; Bousman, Chad; Pereira, Avril; Di Biase, Maria A; Weickert, Thomas W; Weickert, Cynthia Shannon; Pantelis, Christos; Zalesky, Andrew

2017-03-01

Although brain changes in schizophrenia have been proposed to mirror those found with advancing age, the trajectory of gray matter and white matter changes during the disease course remains unclear. The authors sought to measure whether these changes in individuals with schizophrenia remain stable, are accelerated, or are diminished with age. Gray matter volume and fractional anisotropy were mapped in 326 individuals diagnosed with schizophrenia or schizoaffective disorder and in 197 healthy comparison subjects aged 20-65 years. Polynomial regression was used to model the influence of age on gray matter volume and fractional anisotropy at a whole-brain and voxel level. Between-group differences in gray matter volume and fractional anisotropy were regionally localized across the lifespan using permutation testing and cluster-based inference. Significant loss of gray matter volume was evident in schizophrenia, progressively worsening with age to a maximal loss of 8% in the seventh decade of life. The inferred rate of gray matter volume loss was significantly accelerated in schizophrenia up to middle age and plateaued thereafter. In contrast, significant reductions in fractional anisotropy emerged in schizophrenia only after age 35, and the rate of fractional anisotropy deterioration with age was constant and best modeled with a straight line. The slope of this line was 60% steeper in schizophrenia relative to comparison subjects, indicating a significantly faster rate of white matter deterioration with age. The rates of reduction of gray matter volume and fractional anisotropy were significantly faster in males than in females, but an interaction between sex and diagnosis was not evident. The findings suggest that schizophrenia is characterized by an initial, rapid rate of gray matter loss that slows in middle life, followed by the emergence of a deficit in white matter that progressively worsens with age at a constant rate.

The Effect of Microstructure and Pre-strain on the Change in Apparent Young's Modulus of a Dual-Phase Steel

NASA Astrophysics Data System (ADS)

Kupke, A.; Hodgson, P. D.; Weiss, M.

2017-07-01

The elastic recovery in dual-phase (DP) steels is not a linear process and changes with plastic deformation. The level of change in the apparent Young's modulus has been reported to depend on material composition and microstructure, but most previous experimental studies were limited to industrial DP steels and led to contradicting results. This work represents a first fundamental study that investigates the separate and combined effect of phase volume fraction and hardness on the change in apparent Young's modulus in DP steel. A common automotive DP steel (DP780) is heat treated to obtain seven different combinations of martensite and ferrite volume fraction and hardness while keeping the chemical composition as well as the shape of the martensite and ferrite phases unchanged. Loading-unloading tests were performed to analyze the chord modulus at various levels of pre-strain. The results suggest that the point of saturation of the chord modulus with pre-strain depends on the morphology of the microstructure, occurring earlier for microstructures consisting of ferrite grains surrounded by martensite laths. It is further revealed that the reduction of the apparent Young's modulus, which is the difference between the material's initial Young's modulus and the chord modulus, increases with martensite hardness if the martensite volume fraction is kept constant. A higher martensite volume fraction initially elevates the reduction of the apparent Young's modulus. After a critical volume fraction of martensite phase of 35%, a decrease in apparent Young's modulus reduction was observed. A comparison of the plastic unloading strain suggests that the mechanisms leading to a reduction in apparent Young's modulus are strongest for the microstructure consisting of 35% martensite volume fraction.

Electrospinning synthesis and characterization of PLA-PEG-MNPs composite fibrous membranes

NASA Astrophysics Data System (ADS)

Kumar, M.; Klimke, S.; Preiss, A.; Unruh, D.; Wengerowsky, D.; Lehmann, R.; Sindelar, R.; Klingelhöfer, G.; Boča, R.; Renz, F.

2017-11-01

An electrospinning technique was used to fabricate PLA, PLA-PEG and PLA-PEG-MNPs composite fibrous membranes. The morphology of electrospun composite membranes were characterized by scanning electron microscope. To test the potential availability of MNPs in PLA-PEG composite membranes, TG, Raman, Mössbauer, VSM and ICP-OES analysis were used. The PLA-PEG composite fibrous membranes showed the presence of MNPs, hence offers the possibility for magnetically triggered on-demand drug delivery.

Cellular delivery of PEGylated PLGA nanoparticles.

PubMed

Pamujula, Sarala; Hazari, Sidhartha; Bolden, Gevoni; Graves, Richard A; Chinta, Dakshinamurthy Devanga; Dash, Srikanta; Kishore, Vimal; Mandal, Tarun K

2012-01-01

The objective of this study was to investigate the efficiency of uptake of PEGylated polylactide-co-gycolide (PLGA) nanoparticles by breast cancer cells. Nanoparticles of PLGA containing various amounts of polyethylene glycol (PEG, 5%-15%) were prepared using a double emulsion solvent evaporation method. The nanoparticles were loaded with coumarin-6 (C6) as a fluorescence marker. The particles were characterized for surface morphology, particle size, zeta potential, and for cellular uptake by 4T1 murine breast cancer cells. Irrespective of the amount of PEG, all formulations yielded smooth spherical particles. However, a comparison of the particle size of various formulations showed bimodal distribution of particles. Each formulation was later passed through a 1.2 µm filter to obtain target size particles (114-335 nm) with zeta potentials ranging from -2.8 mV to -26.2 mV. While PLGA-PEG di-block (15% PEG) formulation showed significantly higher 4T1 cellular uptake than all other formulations, there was no statistical difference in cellular uptake among PLGA, PLGA-PEG-PLGA tri-block (10% PEG), PLGA-PEG di-block (5% PEG) and PLGA-PEG di-block (10% PEG) nanoparticles. These preliminary findings indicated that the nanoparticle formulation prepared with 15% PEGylated PLGA showed maximum cellular uptake due to it having the smallest particle size and lowest zeta potential. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

PLGA-mPEG nanoparticles of cisplatin: in vitro nanoparticle degradation, in vitro drug release and in vivo drug residence in blood properties.

PubMed

Avgoustakis, K; Beletsi, A; Panagi, Z; Klepetsanis, P; Karydas, A G; Ithakissios, D S

2002-02-19

The in vitro nanoparticle degradation, in vitro drug release and in vivo drug residence in blood properties of PLGA-mPEG nanoparticles of cisplatin were investigated. The nanoparticles were prepared by a double emulsion method and characterized with regard to their morphology, size, zeta potential and drug loading. The rate of in vitro degradation of the PLGA-mPEG nanoparticles in PBS (pH 7.4) depended on their composition, increasing when the mPEG content (mPEG:PLGA ratio) of the nanoparticles increased. Sustained cisplatin release over several hours from the PLGA-mPEG nanoparticles in vitro (PBS) was observed. The composition of the nanoparticles affected drug release: the rate of release increased when the mPEG content of the nanoparticles increased. Within the range of drug loadings investigated, the drug loading of the nanoparticles did not have any significant effect on drug release. The loading efficiency was low and needs improvement in order to obtain PLGA-mPEG nanoparticles with a satisfactory cisplatin content for therapeutic application. The i.v. administration of PLGA-mPEG nanoparticles of cisplatin in BALB/c mice resulted in prolonged cisplatin residence in systemic blood circulation. The results appear to justify further investigation of the suitability of the PLGA-mPEG nanoparticles for the controlled i.v. delivery and/or targeting of cisplatin.

A method to optimize PEG-coating of red blood cells.

PubMed

Hashemi-Najafabadi, Sameereh; Vasheghani-Farahani, Ebrahim; Shojaosadati, Seyed Abbas; Rasaee, Mohammad Javad; Armstrong, Jonathan K; Moin, Mostafa; Pourpak, Zahra

2006-01-01

Alloimmunization to donor blood group antigens remains a significant problem in transfusion medicine. A proposed method to overcome donor-recipient blood group incompatibility is to mask the blood group antigens by the covalent attachment of poly(ethylene glycol) (PEG) to the red blood cell (RBC) membrane. Despite much work in the development of PEG-coating of RBCs, there is a paucity of data on the optimization of the PEG-coating technique; it is the aim of this study to determine the optimum conditions for PEG coating using a cyanuric chloride reactive derivative of methoxy-PEG as a model polymer. Activated PEG of molecular mass 5 kDa was covalently attached to human RBCs under various reaction conditions. Inhibition of binding of a blood-type specific antiserum (anti-D) was employed to evaluate the effect of the PEG-coating, quantified by hemocytometry and flow-cytometry. RBC morphology was examined by light and scanning electron microscopy. Statistical analysis of experimental design together with microscopy results showed that the optimum PEGylation conditions are pH = 8.7, temperature = 14 degrees C, and reaction time = 30 min. An optimum concentration of reactive PEG could not be determined. At high polymer concentrations (>25 mg/mL) a predominance of type III echinocytes was observed, and as a result, a concentration of 15 mg/mL is the highest recommended concentration for a linear PEG of molecular mass 5 kDa.

A retention index system for comprehensive two-dimensional gas chromatography using polyethylene glycols.

PubMed

Veenaas, Cathrin; Haglund, Peter

2018-02-09

The characterization and identification of compounds in complex real-world samples is quite difficult and new concepts and workflows are highly desirable. Retention indices (RIs) are widely used in gas chromatography (GC) to support the identification of unknown compounds. Several attempts have been made to introduce a similar concept for the second dimension in comprehensive two-dimensional (2D) GC (GC × GC) but, an easily applicable and robust system remains elusive. In the present study, a new RI system for GC × GC was developed. Polyethylene glycols (PEGs) were used in combination with a simple linear regression, with n-alkanes as reference points for virtually unretained compounds and PEG homologs as reference compounds for second-dimension RIs (PEG- 2 I). The n-alkanes were assigned a PEG- 2 I of zero and the distance between consecutive PEG homologs from PEG-2 (diethylene glycol) and higher were assigned a PEG- 2 I value of 10. We used ethylene glycol and PEG-2 through PEG-10 as reference compounds, thereby covering a PEG- 2 I range from 20.0 for ethylene glycol, over 50.0 for diethylene glycol (PEG-2) to 130.0 for decaethylene glycol (PEG-10); additional PEGs can be added to cover a wider polarity range. The PEG- 2 I system was initially evaluated using a 30 m × 0.25 mm non-polar (5% phenyl, 0.25 μm film thickness) first-dimension column and a 1.6 m × 0.18 mm polar (50% phenyl, 0.18 μm film thickness) second-dimension column. This system was validated for use with non-polar first-dimension columns and a semi-polar (50% phenyl) second-dimension column, and exhibited robustness to changes in the carrier gas flow velocity, oven temperature ramping rate, and secondary oven temperature offset. An average relative standard deviation of 2.7%, equal to a 95% confidence interval of 1.27 PEG- 2 I units, was obtained for the PEG- 2 I values of 72 environmental pollutants. Additionally, the system was found to be applicable over a wide range of boiling points (in the current case, from n-heptane to n-dotriacontane (C 7 -C 32 )) and can be used with various column dimensions. Changing the second-dimension column to either a narrower 0.1 mm column or a wider 0.25 mm column, yielded similar 95%-percentiles to that of the 0.18 mm column, differing by only 3.20 and 2.80 PEG- 2 I units, respectively. Moreover, methods for improving the system were suggested. Copyright © 2017 Elsevier B.V. All rights reserved.

Anaphylactic reaction to polyethylene-glycol conjugated-asparaginase: premedication and desensitization may not be sufficient.

PubMed

Sahiner, Umit M; Yavuz, S Tolga; Gökce, Muge; Buyuktiryaki, Betul; Altan, Ilhan; Aytac, Selin; Tuncer, Murat; Tuncer, Ayfer; Sackesen, Cansin

2013-08-01

In hypersensitive reactions to native L-asparaginase, either premedication and desensitization or substitution with polyethylene glycol conjugated asparaginase (PEG-ASP) is preferred. Anaphylaxis with PEG-ASP is rare. An 8-year-old girl and a 2.5-year-old boy, both diagnosed as having acute lymphoblastic leukemia, presented with native L-asparaginase hypersensitivity and substitution with PEG-ASP was preferred. They received a premedication (methylprednisolone, hydroxyzine and ranitidine) followed by desensitization with PEG-ASP infusion. Both patients developed anaphylaxis with peg-asparaginase. These are the first reported cases of anaphylactic reaction to PEG-ASP, despite the application of both premedication and desensitization. Anaphylaxis with PEG-ASP is very rare and premedication and desensitization protocols may not prevent these hypersensitive reactions. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

Site-Specific Albumination as an Alternative to PEGylation for the Enhanced Serum Half-Life in Vivo.

PubMed

Yang, Byungseop; Lim, Sung In; Kim, Jong Chul; Tae, Giyoong; Kwon, Inchan

2016-05-09

Polyethylene glycol (PEG) has been widely used as a serum half-life extender of therapeutic proteins. However, due to immune responses and low degradability of PEG, developing serum half-life extender alternatives to PEG is required. Human serum albumin (HSA) has several beneficial features as a serum half-life extender, including a very long serum half-life, good degradability, and low immune responses. In order to further evaluate the efficacy of HSA, we compared the extent of serum half-life extension of a target protein, superfolder green fluorescent protein (sfGFP), upon HSA conjugation with PEG conjugation side-by-side. Combination of site-specific incorporation of p-azido-l-phenylalanine into sfGFP and copper-free click chemistry achieved the site-specific conjugation of a single HSA, 20 kDa PEG, or 30 kDa PEG to sfGFP. These sfGFP conjugates exhibited the fluorescence comparable to or even greater than that of wild-type sfGFP (sfGFP-WT). In mice, HSA-conjugation to sfGFP extended the serum half-life 9.0 times compared to that of unmodified sfGFP, which is comparable to those of PEG-conjugated sfGFPs (7.3 times for 20 kDa PEG and 9.5 times for 30 kDa PEG). These results clearly demonstrated that HSA was as effective as PEG in extending the serum half-life of a target protein. Therefore, with the additional favorable features, HSA is a good serum half-life extender of a (therapeutic) protein as an alternative to PEG.

Adenovirus vector covalently conjugated to polyethylene glycol with a cancer-specific promoter suppresses the tumor growth through systemic administration.

PubMed

Yao, Xinglei; Yoshioka, Yasuo; Morishige, Tomohiro; Eto, Yusuke; Narimatsu, Shogo; Mizuguchi, Hiroyuki; Mukai, Yohei; Okada, Naoki; Nakagawa, Shinsaku

2010-01-01

Cancer gene therapy with adenovirus vectors (Adv) is limited to local administration because systemic administration of Adv produces a weak therapeutic effect and severe side effects. Previously, we generated a dual cancer-specific Adv system by using Adv covalently conjugated to polyethylene glycol (PEG) for transductional targeting and the telomere reverse transcriptase (TERT) promoter as a cancer-specific promoter for transcriptional targeting (PEG-Ad-TERT). We demonstrated that systemic administration of PEG-Ad-TERT showed superior antitumor effects against lung metastatic cancer with negligible side effects. Here, we investigated the therapeutic efficacy of systemic administration of PEG-Ad-TERT for the treatment of primary tumors. We first evaluated the transgene expression of PEG-Ad-TERT containing the luciferase gene (PEG-Ad-TERT/Luc) in primary tumors. Systemic administration of PEG-Ad-TERT/Luc resulted high transgene expression, similar to that observed in tumors for the conventional cytomegalovirus (CMV) promoter-driven Adv containing the luciferase gene (Ad-CMV/Luc). By comparison, transgene expression was 2500-fold lower than that of Ad-CMV/Luc in liver. We then examined the therapeutic effect of systemic administration of PEG-Ad-TERT containing the herpes simplex virus thymidine kinase (HSVtk) gene (PEG-Ad-TERT/HSVtk) for the treatment of primary tumors. We showed that PEG-Ad-TERT/HSVtk produced a notable antitumor effect against primary tumors with negligible side effects. These results demonstrated that PEG-Ad-TERT can be regarded as a prototype Adv with suitable efficacy and safety for systemic cancer gene therapy against both metastatic and primary tumors.

Synthesis of linear and cyclic peptide-PEG-lipids for stabilization and targeting of cationic liposome-DNA complexes.

PubMed

Ewert, Kai K; Kotamraju, Venkata Ramana; Majzoub, Ramsey N; Steffes, Victoria M; Wonder, Emily A; Teesalu, Tambet; Ruoslahti, Erkki; Safinya, Cyrus R

2016-03-15

Because nucleic acids (NAs) have immense potential value as therapeutics, the development of safe and effective synthetic NA vectors continues to attract much attention. In vivo applications of NA vectors require stabilized, nanometer-scale particles, but the commonly used approaches of steric stabilization with a polymer coat (e.g., PEGylation; PEG=poly(ethylene glycol)) interfere with attachment to cells, uptake, and endosomal escape. Conjugation of peptides to PEG-lipids can improve cell attachment and uptake for cationic liposome-DNA (CL-DNA) complexes. We present several synthetic approaches to peptide-PEG-lipids and discuss their merits and drawbacks. A lipid-PEG-amine building block served as the common key intermediate in all synthetic routes. Assembling the entire peptide-PEG-lipid by manual solid phase peptide synthesis (employing a lipid-PEG-carboxylic acid) allowed gram-scale synthesis but is mostly applicable to linear peptides connected via their N-terminus. Conjugation via thiol-maleimide or strain-promoted (copper-free) azide-alkyne cycloaddition chemistry is highly amenable to on-demand preparation of peptide-PEG-lipids, and the appropriate PEG-lipid precursors are available in a single chemical step from the lipid-PEG-amine building block. Azide-alkyne cycloaddition is especially suitable for disulfide-bridged peptides such as iRGD (cyclic CRGDKGPDC). Added at 10 mol% of a cationic/neutral lipid mixture, the peptide-PEG-lipids stabilize the size of CL-DNA complexes. They also affect cell attachment and uptake of nanoparticles in a peptide-dependent manner, thereby providing a platform for preparing stabilized, affinity-targeted CL-DNA nanoparticles. Copyright © 2016 Elsevier Ltd. All rights reserved.

Characterization, efficacy, pharmacokinetics, and biodistribution of 5kDa mPEG modified tetrameric canine uricase variant.

PubMed

Zhang, Chun; Fan, Kai; Luo, Hua; Ma, Xuefeng; Liu, Riyong; Yang, Li; Hu, Chunlan; Chen, Zhenmin; Min, Zhiqiang; Wei, Dongzhi

2012-07-01

PEGylated uricase is a promising anti-gout drug, but the only commercially marketed 10kDa mPEG modified porcine-like uricase (Pegloticase) can only be used for intravenous infusion. In this study, tetrameric canine uricase variant was modified by covalent conjugation of all accessible ɛ amino sites of lysine residues with a smaller 5kDa mPEG (mPEG-UHC). The average modification degree and PEGylation homogeneity were evaluated. Approximately 9.4 5 kDa mPEG chains were coupled to each monomeric uricase and the main conjugates contained 7-11 mPEG chains per subunit. mPEG-UHC showed significantly therapeutic or preventive effect on uric acid nephropathy and acute urate arthritis based on three different animal models. The clearance rate from an intravenous injection of mPEG-UHC varied significantly between species, at 2.61 mL/h/kg for rats and 0.21 mL/h/kg for monkeys. The long elimination half-life of mPEG-UHC in non-human primate (191.48 h, intravenous injection) indicated the long-term effects in humans. Moreover, the acceptable bioavailability of mPEG-UHC after subcutaneous administration in monkeys (94.21%) suggested that subcutaneous injection may be regarded as a candidate administration route in clinical trails. Non-specific tissue distribution was observed after administration of (125)I-labeled mPEG-UHC in rats, and elimination by the kidneys into the urine is the primary excretion route. Copyright © 2012 Elsevier B.V. All rights reserved.

Influence of anchoring ligands and particle size on the colloidal stability and in vivo biodistribution of polyethylene glycol-coated gold nanoparticles in tumor-xenografted mice

PubMed Central

Zhang, Guodong; Yang, Zhi; Lu, Wei; Zhang, Rui; Huang, Qian; Tian, Mei; Li, Li; Liang, Dong; Li, Chun

2009-01-01

Polyethylene glycol (PEG)-coated (pegylated) gold nanoparticles (AuNPs) have been proposed as drug carriers and diagnostic contrast agents. However, the impact of particle characteristics on the biodistribution and pharmacokinetics of pegylated AuNPs is not clear. We investigated the effects of PEG molecular weight, type of anchoring ligand, and particle size on the assembly properties and colloidal stability of PEG-coated AuNPs. The pharmacokinetics and biodistribution of the most stable PEG-coated AuNPs in nude mice bearing subcutaneous A431 squamous tumors were further studied using 111In-labeled AuNPs. AuNPs coated with thioctic acid (TA)-anchored PEG exhibited higher colloidal stability in phosphate-buffered saline in the presence of dithiothreitol than did AuNPs coated with monothiol-anchored PEG. AuNPs coated with high-molecular-weight (5000 Da) PEG were more stable than AuNPs coated with low-molecular-weight (2000 Da) PEG. Of the 20-nm, 40-nm, and 80-nm AuNPs coated with TA-terminated PEG5000, the 20-nm AuNPs exhibited the lowest uptake by reticuloendothelial cells and the slowest clearance from the body. Moreover, the 20-nm AuNPs coated with TA-terminated PEG5000 showed significantly higher tumor uptake and extravasation from the tumor blood vessels than did the 40- and 80-nm AuNPs. Thus, 20-nm AuNPs coated with TA-terminated PEG5000 are promising potential drug delivery vehicles and diagnostic imaging agents. PMID:19131103

Investigation of the role of hydrophilic chain length in amphiphilic perfluoropolyether/poly(ethylene glycol) networks: towards high-performance antifouling coatings.

PubMed

Wang, Yapei; Pitet, Louis M; Finlay, John A; Brewer, Lenora H; Cone, Gemma; Betts, Douglas E; Callow, Maureen E; Callow, James A; Wendt, Dean E; Hillmyer, Marc A; DeSimonea, Joseph M

2011-01-01

The facile preparation of amphiphilic network coatings having a hydrophobic dimethacryloxy-functionalized perfluoropolyether (PFPE-DMA; M(w) = 1500 g mol(-1)) crosslinked with hydrophilic monomethacryloxy functionalized poly(ethylene glycol) macromonomers (PEG-MA; M(w) = 300, 475, 1100 g mol(-1)), intended as non-toxic high-performance marine coatings exhibiting antifouling characteristics is demonstrated. The PFPE-DMA was found to be miscible with the PEG-MA. Photo-cured blends of these materials containing 10 wt% of PEG-MA oligomers did not swell significantly in water. PFPE-DMA crosslinked with the highest molecular weight PEG oligomer (ie PEG1100) deterred settlement (attachment) of algal cells and cypris larvae of barnacles compared to a PFPE control coating. Dynamic mechanical analysis of these networks revealed a flexible material. Preferential segregation of the PEG segments at the polymer/air interface resulted in enhanced antifouling performance. The cured amphiphilic PFPE/PEG films showed decreased advancing and receding contact angles with increasing PEG chain length. In particular, the PFPE/PEG1100 network had a much lower advancing contact angle than static contact angle, suggesting that the PEG1100 segments diffuse to the polymer/water interface quickly. The preferential interfacial aggregation of the larger PEG segments enables the coating surface to have a substantially enhanced resistance to settlement of spores of the green seaweed Ulva, cells of the diatom Navicula and cypris larvae of the barnacle Balanus amphitrite as well as low adhesion of sporelings (young plants) of Ulva, adhesion being lower than to a polydimethyl elastomer, Silastic T2.

Effects of the aging temperature and stress relaxation conditions on γ‧ precipitation in Inconel X-750

NASA Astrophysics Data System (ADS)

Ha, Jeong Won; Seong, Baek Seok; Jeong, Hi Won; Choi, Yoon Suk; Kang, Namhyun

2015-02-01

Inconel X-750 is a Ni-based precipitation-hardened superalloy typically used in springs designed for high-temperature applications such as the hold-down springs in nuclear power plants. γ‧ is a major precipitate in X-750 alloys which affects the strength, creep resistance, and stress relaxation properties of the spring. In this study, a solution-treated X-750 wire coiled into a spring was used that was aged at various temperatures and submitted to stress relaxation tests with and without loading. Small angle neutron scattering was employed to quantify the size and volume fraction of γ‧ phase in the springs as a function of the aging temperature and the application of a load during stress relaxation. The volume fraction of γ‧ precipitates increased in the specimen aged at 732 °C following stress relaxation at 500 °C for 300 h. However, the mean size of the precipitates in the samples was not affected by stress relaxation. The specimen aged at the lower temperature (620 °C) contained a smaller γ‧ volume fraction and gained a smaller fraction of γ‧ during stress relaxation compared with the sample aged at the higher temperature (732 °C). The smaller increase in the γ‧ volume fraction for the sample aged at 620 °C was associated with a larger increase in the M23C6 secondary carbide content during relaxation. The Cr depletion zone around the secondary carbides raises the solubility of γ‧ thereby decreasing the volume fraction of γ‧ precipitates in Inconel X-750. In terms of stress relaxation, a larger increase in the γ‧ volume fraction was measured with loading rather than without. This is probably associated with the dislocation accumulation generated under loading that facilitate the nucleation and growth of heterogeneous γ‧ phase due to enhanced diffusion.

Characterization, degradation, and mechanical strength of poly(D,L-lactide-co-epsilon-caprolactone)-poly(ethylene glycol)-poly(D,L-lactide-co-epsilon-caprolactone).

PubMed

Bramfeldt, Hanna; Sarazin, Pierre; Vermette, Patrick

2007-11-01

A series of three biocompatible P(CL-co-LA)-PEG-P(CL-co-LA) copolymers were synthesized using ring-opening polymerization and characterized by 1H-NMR, gel permeation chromatography, DSC, dynamic-mechanical analysis, and X-ray diffraction. The number of monomer units was kept constant, while the D,L-LA fraction was varied so as to constitute 0, 30, or 70% of the end segments. The molecular weights were sufficiently high to eventually permit 3D scaffold preparation. A degradation study was carried out over 26 weeks, and the effect of monomer composition on the rate of degradation as well as on changes in mechanical strength was investigated. Pure polycaprolactone (PCL)-poly(ethylene glycol) (PEG)-PCL copolymer, P(100/0), was a crystalline material displaying no measurable mass loss, a 30% reduction in mean molecular weight (Mn), and only very slight changes in tensile strength. The random incorporation of 30 and 70% D,L-LA into the end sections of the polymer chain, produced more and more amorphous materials, exhibiting increasingly high rates of degradation, mass loss, and loss of tensile strength. Compared with random P(CL-co-LA), the presence of the PEG block was found both to improve hydrophilicity and thus the rate of degradation and to infer a stabilizing quality, thereby pacing the decrease in tensile strength during degradation. The tested copolymers range from materials exhibiting low mechanical strength and high rate of degradation to slow-degrading materials with high mechanical strength suitable, e.g., for three-dimensional scaffolding. Copyright (c) 2007 Wiley Periodicals, Inc.

Effects of temperature and particles concentration on the dynamic viscosity of MgO-MWCNT/ethylene glycol hybrid nanofluid: Experimental study

NASA Astrophysics Data System (ADS)

Soltani, Omid; Akbari, Mohammad

2016-10-01

In this paper, the effects of temperature and particles concentration on the dynamic viscosity of MgO-MWCNT/ethylene glycol hybrid nanofluid is examined. The experiments carried out in the solid volume fraction range of 0 to 1.0% under the temperature ranging from 30 °C to 60 °C. The results showed that the hybrid nanofluid behaves as a Newtonian fluid for all solid volume fractions and temperatures considered. The measurements also indicated that the dynamic viscosity increases with increasing the solid volume fraction and decreases with the temperature rising. The relative viscosity revealed that when the solid volume fraction enhances from 0.1 to 1%, the dynamic viscosity increases up to 168%. Finally, using experimental data, in order to predict the dynamic viscosity of MgO-MWCNT/ethylene glycol hybrid nanofluids, a new correlation has been suggested. The comparisons between the correlation outputs and experimental results showed that the suggested correlation has an acceptable accuracy.

Size distribution and volume fraction of T(1) phase precipitates from TEM images: Direct measurements and related correction.

PubMed

Dorin, Thomas; Donnadieu, Patricia; Chaix, Jean-Marc; Lefebvre, Williams; Geuser, Frédéric De; Deschamps, Alexis

2015-11-01

Transmission Electron Microscopy (TEM) can be used to measure the size distribution and volume fraction of fine scale precipitates in metallic systems. However, such measurements suffer from a number of artefacts that need to be accounted for, related to the finite thickness of the TEM foil and to the projected observation in two dimensions of the microstructure. We present a correction procedure to describe the 3D distribution of disc-like particles and apply this method to the plate-like T1 precipitates in an Al-Li-Cu alloy in two ageing conditions showing different particle morphologies. The precipitates were imaged in a High-Angular Annular Dark Field Microscope (HAADF-STEM). The corrected size distribution is further used to determine the precipitate volume fraction. Atom probe tomography (APT) is finally utilised as an alternative way to measure the precipitate volume fraction and test the validity of the electron microscopy results. Copyright © 2015 Elsevier Ltd. All rights reserved.

Computer Simulation of Spatial Arrangement and Connectivity of Particles in Three-Dimensional Microstructure: Application to Model Electrical Conductivity of Polymer Matrix Composite

NASA Technical Reports Server (NTRS)

Louis, P.; Gokhale, A. M.

1996-01-01

Computer simulation is a powerful tool for analyzing the geometry of three-dimensional microstructure. A computer simulation model is developed to represent the three-dimensional microstructure of a two-phase particulate composite where particles may be in contact with one another but do not overlap significantly. The model is used to quantify the "connectedness" of the particulate phase of a polymer matrix composite containing hollow carbon particles in a dielectric polymer resin matrix. The simulations are utilized to estimate the morphological percolation volume fraction for electrical conduction, and the effective volume fraction of the particles that actually take part in the electrical conduction. The calculated values of the effective volume fraction are used as an input for a self-consistent physical model for electrical conductivity. The predicted values of electrical conductivity are in very good agreement with the corresponding experimental data on a series of specimens having different particulate volume fraction.

Cost analysis of cetuximab (Erbitux) plus radiotherapy (ERT) versus concomitant cisplatin plus radiotherapy (CRT) within an NHS oncology unit (single institution): a pilot study

PubMed Central

Sundus, Yahya; Dawn, Dawson; Carol, Glaister; Susan, Merrick

2016-01-01

Objective: The aim of this feasibility study is to define the resource effectiveness of cetuximab vs cisplatin given concomitantly with radiotherapy for squamous cell carcinoma within a National Health Service clinical oncology unit. Methods: 20 patients with Stage 3 or 4 head and neck squamous cell cancers were randomized to receive either cetuximab with radiotherapy (ERT) or cisplatin with radiotherapy concurrent with external beam radiotherapy 70 Gy in 35 fractions on a 1 : 1 basis over a 12-month duration. The study compared the resource utilization of ERT vs cisplatin with radiotherapy taking into account drug costs, clinical management and the costs of managing treatment-related toxicity from first fraction of radiotherapy to 6 months after the completion of therapy. Outcome measures were quality of life (recorded at the entry, end of radiotherapy, 6 weeks post treatment and 6 months post treatment), admissions to hospital, delays to radiotherapy, locoregional control and survival. Results: Total drug costs including cost of nutritional supplements for patients treated with cetuximab were £7407.45 compared with £3959.07 for patients treated with cisplatin. Unscheduled admissions for toxicity management were significantly more common in the ERT arm. Healthcare personnel spent significantly more time delivering unscheduled outpatient care for patients receiving cisplatin than for those receiving cetuximab (p = 0.01). No significant difference in the quality of life was suggested at baseline, 6 weeks and 6 months. The mean time to removal of percutaneous gastrostomy (PEG) after completion of radiotherapy was 49.7 weeks in the cisplatin arm and 18.5 weeks in the cetuximab arm (p = 0.04). There was a statistically significant difference in patient-reported use of PEG between the cisplatin and cetuximab arms at 6 months following completion of treatment (p = 0.04). At 21 months, overall survival was 80% in the cisplatin arm vs 50% in the cetuximab (p = 0.332), with disease-free survival being 80% in the cisplatin arm vs 40% in the cetuximab (p = 0.097). Conclusion: Cetuximab is still more expensive in simple drug cost terms than cisplatin when delivered with radiotherapy taking into account costs of drugs for toxicity management and nutritional supplements but other resource implications such as inpatient admission, time spent delivering unscheduled care and cost of additional investigations to manage toxicity for patients treated with cisplatin significantly reduce differential. The study suggested significant differences in patient-reported PEG use at 6 months and in time to PEG removal in favour of the cetuximab arm. Advances in knowledge: There is paucity of randomized data on cost analysis for cisplatin vs cetuximab radiotherapy; this trial informs on the cost analysis between the two approaches. PMID:27734748

A study of fiber volume fraction effects in notched unidirectional SCS-6/Ti-15V-3Cr-3Al-3Sn composite. Ph.D. Thesis Final Report

NASA Technical Reports Server (NTRS)

Covey, Steven J.

1993-01-01

Notched unidirectional SCS-6/Ti-15-3 composite of three different fiber volume fractions (vf = 0.15, 0.37, and 0.41) was investigated for various room temperature microstructural and material properties including: fatigue crack initiation, fatigue crack growth, and fracture toughness. While the matrix hardness is similar for all fiber volume fractions, the fiber/matrix interfacial shear strength and matrix residual stress increases with fiber volume fraction. The composite fatigue crack initiation stress is shown to be matrix controlled and occurs when the net maximum matrix stress approaches the endurance limit stress of the matrix. A model is presented which includes residual stresses and presents the composite initiation stress as a function of fiber volume fraction. This model predicts a maximum composite initiation stress at vf approximately 0.15 which agrees with the experimental data. The applied composite stress levels were increased as necessary for continued crack growth. The applied Delta(K) values at crack arrest increase with fiber volume fraction by an amount better approximated using an energy based formulation rather than when scaled linear with modulus. After crack arrest, the crack growth rate exponents for vf37 and vf41 were much lower and toughness much higher, when compared to the unreinforced matrix, because of the bridged region which parades with the propagating fatigue crack. However, the vf15 material exhibited a higher crack growth rate exponent and lower toughness than the unreinforced matrix because once the bridged fibers nearest the crack mouth broke, the stress redistribution broke all bridged fibers, leaving an unbridged crack. Degraded, unbridged behavior is modeled using the residual stress state in the matrix ahead of the crack tip. Plastic zone sizes were directly measured using a metallographic technique and allow prediction of an effective matrix stress intensity which agrees with the fiber pressure model if residual stresses are considered. The sophisticated macro/micro finite element models of the 0.15 and 0.37 fiber volume fractions presented show good agreement with experimental data and the fiber pressure model when an estimated effective fiber/matrix debond length is used.

Effects of laser fluence non-uniformity on ambient-temperature soot measurements using the auto-compensating laser-induced incandescence technique

NASA Astrophysics Data System (ADS)

Liu, Fengshan; Rogak, Steven; Snelling, David R.; Saffaripour, Meghdad; Thomson, Kevin A.; Smallwood, Gregory J.

2016-11-01

Multimode pulsed Nd:YAG lasers are commonly used in auto-compensating laser-induced incandescence (AC-LII) measurements of soot in flames and engine exhaust as well as black carbon in the atmosphere. Such lasers possess a certain degree of fluence non-uniformity across the laser beam even with the use of beam shaping optics. Recent research showed that the measured volume fraction of ambient-temperature soot using AC-LII increases significantly, by about a factor of 5-8, with increasing the laser fluence in the low-fluence regime from a very low fluence to a relatively high fluence of near sublimation. The causes of this so-called soot volume fraction anomaly are currently not understood. The effects of laser fluence non-uniformity on the measured soot volume fraction using AC-LII were investigated. Three sets of LII experiments were conducted in the exhaust of a MiniCAST soot generator under conditions of high elemental carbon using Nd:YAG lasers operated at 1064 nm. The laser beams were shaped and relay imaged to achieve a relatively uniform fluence distribution in the measurement volume. To further homogenize the laser fluence, one set of LII experiments was conducted by using a diffractive optical element. The measured soot volume fractions in all three sets of LII experiments increase strongly with increasing the laser fluence before a peak value is reached and then start to decrease at higher fluences. Numerical calculations were conducted using the experimental laser fluence histograms. Laser fluence non-uniformity is found partially responsible for the soot volume fraction anomaly, but is insufficient to explain the degree of soot volume fraction anomaly observed experimentally. Representing the laser fluence variations by a histogram derived from high-resolution images of the laser beam energy profile gives a more accurate definition of inhomogeneity than a simple averaged linear profile across the laser beam.

Free volume of mixed cation borosilicate glass sealants elucidated by positron annihilation lifetime spectroscopy and its correlation with glass properties

NASA Astrophysics Data System (ADS)

Ojha, Prasanta K.; Rath, Sangram K.; Sharma, Sandeep K.; Sudarshan, Kathi; Pujari, Pradeep K.; Chongdar, Tapas K.; Gokhale, Nitin M.

2015-01-01

The role of La+3/Sr+2 ratios, which is varied from 0.08 to 5.09, on density, molar volume, packing fraction, free volume, thermal and electrical properties in strontium lanthanum aluminoborosilicate based glass sealants intended for solid oxide fuel cell (SOFC) applications is evaluated. The studies reveal expansion of the glass network evident from increasing molar volume and decreasing packing fraction of glasses with progressive La+3 substitutions. The molecular origin of these macroscopic structural features can be accounted for by the free volume parameters measured from positron annihilation lifetime spectroscopy (PALS). The La+3 induced expanded glass networks show increased number of subnanoscopic voids with larger sizes, as revealed from the ortho-positronium (o-Ps) lifetime and its intensity. A remarkably direct correspondence between the molar volume and fractional free volume trend is established with progressive La2O3 substitution in the glasses. The effect of these structural changes on the glass transition temperature, softening temperature, coefficient of thermal expansion, thermal stability as well as electrical conductivity has been studied.

A Solar Volumetric Receiver: Influence of Absorbing Cells Configuration on Device Thermal Performance

NASA Astrophysics Data System (ADS)

Yilbas, B. S.; Shuja, S. Z.

2017-01-01

Thermal performance of a solar volumetric receiver incorporating the different cell geometric configurations is investigated. Triangular, hexagonal, and rectangular absorbing cells are incorporated in the analysis. The fluid volume fraction, which is the ratio of the volume of the working fluid over the total volume of solar volumetric receiver, is introduced to assess the effect of cell size on the heat transfer rates in the receiver. In this case, reducing the fluid volume fraction corresponds to increasing cell size in the receiver. SiC is considered as the cell material, and air is used as the working fluid in the receiver. The Lambert's Beer law is incorporated to account for the solar absorption in the receiver. A finite element method is used to solve the governing equation of flow and heat transfer. It is found that the fluid volume fraction has significant effect on the flow field in the solar volumetric receiver, which also modifies thermal field in the working fluid. The triangular absorbing cell gives rise to improved effectiveness of the receiver and then follows the hexagonal and rectangular cells. The second law efficiency of the receiver remains high when hexagonal cells are used. This occurs for the fluid volume fraction ratio of 0.5.

FRAC-IN-THE-BOX utilization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Collins, D.G.; West, J.T.

FRAC-IN-THE-BOX is a computer code developed to calculate the fractions of rectangular parallelepiped mesh cell volumes that are intersected by combinatorial geometry type zones. The geometry description used in the code is a subset of the combinatorial geometry used in SABRINA. The input file may be read into SABRINA and three dimensional plots made of the input geometry. The volume fractions for those portions of the geometry that are too complicated to describe with the geometry routines provided in FRAC-IN-THE-BOX may be calculated in SABRINA and merged with the volume fractions computed for the remainder of the geometry. 21 figs.,more » 1 tab.« less

The effect of different fibre volume fraction on mechanical properties of banana/pineapple leaf (PaLF)/glass hybrid composite

NASA Astrophysics Data System (ADS)

Hanafee, Z. M.; Khalina, A.; Norkhairunnisa, M.; Syams, Z. Edi; Liew, K. E.

2017-09-01

This paper investigates the effect of fibre volume fraction on mechanical properties of banana-pineapple leaf (PaLF)-glass reinforced epoxy resin under tensile loading. Uniaxial tensile tests were carried out on specimens with different fibre contents (30%, 40%, 50% in weight). The composite specimens consists of 13 different combinations. The effect of hybridisation between synthetic and natural fibre onto tensile properties was determined and the optimum fibre volume fraction was obtained at 50% for both banana and PaLF composites. Additional 1 layer of woven glass fibre increased the tensile strength of banana-PaLF composite up to 85%.

Co-delivery of docetaxel and gemcitabine using PEGylated self-assembled stealth nanoparticles for improved breast cancer therapy.

PubMed

Kushwah, Varun; Katiyar, Sameer S; Agrawal, Ashish Kumar; Gupta, Ramesh C; Jain, Sanyog

2018-04-20

The present report deals with conjugation of dual drug; docetaxel (DTX) and gemcitabine (GEM) with linker poly-ethylene-glycol (PEG) to develop amphiphilic molecule having self-assembled property. The synthesized conjugate (DTX-PEG-GEM) demonstrated critical micelle concentration (CMC) in the range of 5-10μg/ml which self-assembled to form NPs with size 124.2±5.7. Remarkably higher coumarin-6 (C-6) fluorescence signals observed in case of C-6 loaded NPs, suggested enhanced cellular uptake via clathrin mediated endocytosis. Developed NPs demonstrated 4.8-fold higher AUC (0-∞) value of GEM in comparison with Gemzar®. Tumor growth inhibition study demonstrated significant reduction in tumor volume and higher survival rate with NPs. Moreover, NPs demonstrated significantly lower hepato- and nephro-toxicity, evident from both histopathological sections and biochemical markers level estimation, and hemolytic toxicity. Data in hand suggest enhanced therapeutic efficacy and reduced toxicity of developed NPs over conventional drugs, resulting in efficient combinatorial chemotherapeutic-regimen and patient compliance, which is still an unmet task. Copyright © 2018 Elsevier Inc. All rights reserved.

Investigation of chromatography and polymer/salt aqueous two-phase processes for downstream processing development of recombinant phenylalanine dehydrogenase.

PubMed

Omidinia, Eskandar; Shahbaz Mohamadi, Hamid; Dinarvand, Rassoul; Taherkhani, Heshmat-Allah

2010-03-01

This work presents a comprehensive study between the polymer/salt aqueous two-phase systems (ATPS) and chromatography process for downstream processing of recombinant Bacillus badius phenylalanine dehydrogenase (PheDH). First, the partitioning behavior of recombinant PheDH in polyethylene glycol (PEG)/K2HPO4 ATPS was examined. For comparative purpose, a classical chromatographic protocol was performed as well. Investigation of chromatography and ATPS procedures revealed that the ATPS comprising of 9% (w/w) PEG-6000, 16% (w/w) K2HPO4 and 16% (w/w) KCl with pH of 8.0, volume ratio (V ( R )) of 0.25, temperature of 25 degrees C and 40% (w/w) cell lysate ensured the most favorable approach for PheDH downstream process. A specific activity of 4,231.4 U/mg, a yield of 96.7% and a recovery of 162.0% were obtained. Furthermore, the shorter process time (4 vs. 48 h) and the lower total cost (4 vs. 20 euro) were additionally features that confirmed the suitability of proposed technique.

Adsorption of polyethylene glycol (PEG) onto cellulose nano-crystals to improve its dispersity.

PubMed

Cheng, Dong; Wen, Yangbing; Wang, Lijuan; An, Xingye; Zhu, Xuhai; Ni, Yonghao

2015-06-05

In this work, the adsorption of polyethylene glycol (PEG) onto cellulose nano-crystals (CNC) was investigated for preparing re-dispersible dried CNC. Results showed that the re-dispersity of CNC in water can be significantly enhanced using a PEG1000 dosage of 5wt% (based on the dry weight of CNC). The elemental analysis confirmed the adsorption of PEG onto the CNC surface. Transmission electron microscopy (TEM) was used to characterize the dry powder and indicated that the irreversible agglomeration of CNC after drying was essentially eliminated based on the PEG adsorption concept. Thermo-gravimetric analysis (TGA) and X-ray diffraction (XRD) suggested that CNC crystallinity and thermal stability were not affected by the adsorption of PEG. Thus, the adsorption of PEG has great potential for producing re-dispersible powder CNC. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular dynamics study of the structure and interparticle interactions of polyethylene glycol-conjugated PAMAM dendrimers.

PubMed

Lee, Hwankyu; Larson, Ronald G

2009-10-08

We performed molecular dynamics (MD) simulations of one or two copies of polyethylene glycol of molecular weight 550 (PEG550) and 5000 (PEG5000) daltons, conjugated to generation 3 (G3) to 5 (G5) polyamidoamine (PAMAM) dendrimers with explicit water using a coarse-grained model. We found the radii of gyration of these dendrimer-PEG molecules to be close to those measured in experiments by Hedden and Bauer (Hedden , R. C. ; Bauer , B. J. Macromolecules 2003 , 36 , 1829.). Densely grafted PEG ligands (>50% of the dendrimer surface) extend like brushes, with layer thickness in agreement with theory for starlike polymers. Two dendrimer-PEG complexes in the box drift away from each other, indicating that no aggregation is induced by either short or long PEG chains, conflicting with a recent view that the cytotoxicity of some PEGylated particles might be due to particle aggregation for long PEG lengths.

Preventing Protein Adsorption and Macrophage Uptake of Gold Nanoparticles via a Hydrophobic Shield

PubMed Central

Larson, Timothy A.; Joshi, Pratixa P.; Sokolov, Konstantin

2012-01-01

Polyethylene glycol (PEG) surface coatings are widely used to render stealth properties to nanoparticles in biological applications. There is abundant literature on benefits of PEG coatings and their ability to reduce protein adsorption, to diminish non-specific interactions with cells, and to improve pharmacokinetics, but very little discussion of the limitations of PEG coatings. Here, we show that physiological concentrations of cysteine and cystine can displace methoxy-PEG-thiol molecules from the gold nanoparticle (GNP) surface that leads to protein adsorption and cell uptake in macrophages within 24 hours. Furthermore, we address this problem by incorporating an alkyl linker between the PEG and the thiol moieties that provides a hydrophobic shield layer between the gold surface and the hydrophilic outer PEG layer. The mPEG-alkyl-thiol coating greatly reduces protein adsorption on GNPs and their macrophage uptake. This has important implications for the design of GNP for biological systems. PMID:23009596

Bombesin functionalized 64Cu-copper sulfide nanoparticles for targeted imaging of orthotopic prostate cancer.

PubMed

Cai, Huawei; Xie, Fang; Mulgaonkar, Aditi; Chen, Lihong; Sun, Xiankai; Hsieh, Jer-Tsong; Peng, Fangyu; Tian, Rong; Li, Lin; Wu, Changqiang; Ai, Hua

2018-05-22

To synthesize and evaluate the imaging potential of Bom-PEG-[ 64 Cu]CuS nanoparticles (NPs) in orothotopic prostate tumor. [ 64 Cu]CuS NPs were synthesized in aqueous solution by 64 CuCl 2 and Na 2 S reaction. Then PEG linker with or without bombesin peptide were conjugated to the surface of [ 64 Cu]CuS NPs to produce Bom-PEG-[ 64 Cu]CuS and PEG-[ 64 Cu]CuS NPs. These two kinds of NPs were used for testing specific uptake in prostate cancer cells in vitro and imaging of orthotopic prostate tumor in vivo. Bom-PEG-[ 64 Cu]CuS and PEG-[ 64 Cu]CuS NPs were successfully synthesized with core diameter of approximately 5 nm. Radioactive cellular uptake revealed that Bom-PEG-[ 64 Cu]CuS was able to specifically bind to prostate cancer cells, and the microPET-CT imaging indicated clear visualization of orthotopic prostate tumors. Radiolabeled Bom-PEG-[ 64 Cu]CuS NPs have potential as an ideal agent for orthotopic prostate tumor imaging by microPET-CT.

Development and Validation of a New Near-Infrared Sensor to Measure Polyethylene Glycol (PEG) Concentration in Water.

PubMed

Buzzi, Olivier; Yuan, Shengyang; Routley, Benjamin

2017-06-10

A near-infrared absorption based laser sensor has been designed and validated for the real-time measurement of polyethylene glycol (PEG) concentration. The wavelength was selected after the determination of the absorption spectrum of deionised water and PEG solutions using a Varian Cary 6000i spectrophotometer, in order to limit the influence of PEG molecular mass on the absorption measurement. With this new sensor, the water is treated as the attenuating species and the addition of PEG in water reduces the absorbance of the medium. The concept was validated using three different PEG types (PEG 6,000, 20,000, and 35,000) and it was found that the results follow Beer Lambert's law. The influence of temperature was assessed by testing the PEG 20,000 at four different temperatures that could be encountered in a laboratory environment. The data show a slight temperature influence (increase of absorbance by 8% when the temperature rises from about 20 to about 29 degrees). Following the validation phase conducted ex situ, a prototype of an immersible sensor was built and calibrated for in situ measurements.

X-ray studies of recombinant anti-testosterone Fab fragments: the use of PEG 3350 in crystallization.

PubMed

Valjakka, J; Hemminki, A; Teerinen, T; Takkinen, K; Rouvinen, J

2000-02-01

Recombinant anti-testosterone wild-type Fab fragment and mutant Fab fragments with high binding selectivity developed by protein engineering have been crystallized with and without ligands. Crystals of these Fab fragments were obtained by the vapour-diffusion technique at room temperature using solutions of PEG 3350 with various biological buffers and with a wide pH range. So far, five data sets have been collected from crystals of three Fab-antigen complexes and from two uncomplexed Fab fragments, with resolutions ranging from 2.10 to 3.1 A. Crystallization conditions for Fab fragments were found by using modifications of the low ionic strength PEG 3350 series. Suitable concentrations of PEG 400, MPD and glycerol solutions for use as cryoprotectants in PEG 3350 solutions have been determined. One useful observation was that PEG 3350 is able to work alone as a cryoprotectant. The screening protocol used requires a smaller amount of protein material to achieve auspicious pre-crystals than previously. Results support the claim that PEG 3350 is more suitable for the crystallization of Fab fragments than higher molecular weight PEGs.

An analysis of prognostic factors after percutaneous endoscopic gastrostomy placement in Japanese patients with amyotrophic lateral sclerosis.

PubMed

Nagashima, Kazuaki; Furuta, Natsumi; Makioka, Kouki; Fujita, Yukio; Ikeda, Masaki; Ikeda, Yoshio

2017-05-15

A percutaneous endoscopic gastrostomy (PEG) is an useful intervention for feeding of amyotrophic lateral sclerosis (ALS) patients who have lost oral intake function. The aim of this study was to investigate the risk factors for early death and the survival after PEG placement. A total of 102 ALS patients who underwent PEG placement were enrolled in this study. Patients were divided into two groups; the poor prognosis group included patients who died or needed permanent mechanical ventilation within 30days after PEG placement, and the good prognosis group included patients who did not meet the criteria of the poor prognosis group. Clinical characteristics, respiratory function, and nutritional parameters were compared for the two groups to assess the correlations between clinical and laboratory variables and early death after PEG placement. Multivariate analysis between two groups revealed that higher arterial carbon dioxide pressure (PaCO 2 ) and aphagia before PEG placement were significantly associated with the poor prognosis group. Multivariate analysis for survival also revealed that higher PaCO 2 and shorter duration from onset to PEG placement were significantly associated with shorter survival after PEG placement. In conclusion, respiratory and nutritional parameters are revealed to be important prognostic factors for ALS patients who undergo PEG placement. Copyright © 2017 Elsevier B.V. All rights reserved.

Higher Molecular Weight Polyethylene Glycol Increases Cell Proliferation While Improving Barrier Function in an In Vitro Colon Cancer Model

PubMed Central

Bharadwaj, Shruthi; Vishnubhotla, Ramana; Shan, Sun; Chauhan, Chinmay; Cho, Michael; Glover, Sarah C.

2011-01-01

Polyethylene glycol (PEG) has been previously shown to protect against enteric pathogens and prevent colon cancer invasion. To determine if PEG could indeed protect against previously observed pro-invasive effects of commensal E. coli and EPEC, Caco-2 cells grown in an in vitro model of colon cancer were infected with strains of human commensal E. coli or EPEC and treated with 10% PEG 3350, PEG 8000, and PEG 20,000, respectively. At 24 hours after infection, MMP-1 and MMP-13 activities, cell cluster thickness, depth of invasion, and proliferation were determined using standard molecular biology techniques and advanced imaging. We found that higher molecular weight PEG, especially PEG 8000 and 20,000, regardless of bacterial infection, increased proliferation and depth of invasion although a decrease in cellular density and MMP-1 activity was also noted. Maximum proliferation and depth of invasion of Caco-2 cells was observed in scaffolds treated with a combination of commensal E. coli strain, HS4 and PEG 8000. In conclusion, we found that PEG 8000 increased cell proliferation and led to the preservation of cell density in cells treated with commensal bacteria. This is important, because the preservation of a proliferative response in colon cancer results in a more chemo-responsive tumor. PMID:21976966

Higher molecular weight polyethylene glycol increases cell proliferation while improving barrier function in an in vitro colon cancer model.

PubMed

Bharadwaj, Shruthi; Vishnubhotla, Ramana; Shan, Sun; Chauhan, Chinmay; Cho, Michael; Glover, Sarah C

2011-01-01

Polyethylene glycol (PEG) has been previously shown to protect against enteric pathogens and prevent colon cancer invasion. To determine if PEG could indeed protect against previously observed pro-invasive effects of commensal E. coli and EPEC, Caco-2 cells grown in an in vitro model of colon cancer were infected with strains of human commensal E. coli or EPEC and treated with 10% PEG 3350, PEG 8000, and PEG 20,000, respectively. At 24 hours after infection, MMP-1 and MMP-13 activities, cell cluster thickness, depth of invasion, and proliferation were determined using standard molecular biology techniques and advanced imaging. We found that higher molecular weight PEG, especially PEG 8000 and 20,000, regardless of bacterial infection, increased proliferation and depth of invasion although a decrease in cellular density and MMP-1 activity was also noted. Maximum proliferation and depth of invasion of Caco-2 cells was observed in scaffolds treated with a combination of commensal E. coli strain, HS4 and PEG 8000. In conclusion, we found that PEG 8000 increased cell proliferation and led to the preservation of cell density in cells treated with commensal bacteria. This is important, because the preservation of a proliferative response in colon cancer results in a more chemo-responsive tumor.

The Influence of Polyethylene Glycol Solution on the Dissolution Rate of Sustained Release Morphine.

PubMed

Hodgman, Michael; Holland, Michael G; Englich, Ulrich; Wojcik, Susan M; Grant, William D; Leitner, Erich

2016-12-01

Whole bowel irrigation (WBI) is a management option for overdose of medications poorly adsorbed to activated charcoal, with modified release properties, or for body packers. Polyethylene glycol (PEG) is a mixture of ethylene oxide polymers of varying molecular weight. PEG with an average molecular weight of 3350 g/mol is used for WBI. PEG electrolyte lavage solution has been shown in vitro to hasten the dissolution of acetaminophen. The impact of PEG on the pharmacokinetics of extended release pharmaceuticals is unknown. Lower average molecular weight PEG mixtures are used as solvents and excipients. We sought to investigate the impact of PEG on the release of morphine from several extended release morphine formulations. An in vitro gastric model was developed. To test the validity of our model, we first investigated the previously described interaction of ethanol and Avinza®. Once demonstrated, we then investigated the effect of PEG with several extended release morphine formulations. In the validation portion of our study, we confirmed an ethanol Avinza® interaction. Subsequently, we did not observe accelerated release of morphine from Avinza® or generic extended release morphine in the presence of PEG. The use of PEG for gastric decontamination following ingestion of these extended release morphine formulations is unlikely to accelerate morphine release and aggravate intoxication.

Urinary excretion of polyethylene glycol 3350 during colonoscopy preparation.

PubMed

Rothfuss, K S; Bode, J C; Stange, E F; Parlesak, A

2006-02-01

Whole gut lavage with a polyethylene glycol electrolyte solution (PEG) is a common bowel cleansing method for diagnostic and therapeutic colon interventions. Absorption of orally administered PEG from the gastrointestinal tract in healthy human beings is generally considered to be poor. In patients with inflammatory bowel disease (IBD), intestinal permeability and PEG absorption were previously reported to be higher than in normal subjects. In the current study, we investigated the absorption of PEG 3350 in patients undergoing routine gut lavage. Urine specimens were collected for 8 hours in 24 patients undergoing bowel cleansing with PEG 3350 for colonoscopy. The urinary excretion of PEG 3350, measured by size exclusion chromatography, ranged between 0.01 and 0.51 % of the ingested amount, corresponding to 5.8 and 896 mg in absolute amounts, respectively. Mean PEG excretion in patients with impaired mucosa such as inflammation or ulceration of the intestine (0.24 % +/- 0.19, n = 11) was not significantly higher (p = 0.173) compared to that in subjects with macroscopically normal intestinal mucosa (0.13 % +/- 0.13, n = 13). The results indicate that intestinal absorption of PEG 3350 is higher than previously assumed and underlies a strong inter-individual variation. Inflammatory changes of the intestine do not necessarily lead to a significantly higher permeability of PEG.

Polyethylene glycol binding alters human telomere G-quadruplex structure by conformational selection

PubMed Central

Buscaglia, Robert; Miller, M. Clarke; Dean, William L.; Gray, Robert D.; Lane, Andrew N.; Trent, John O.; Chaires, Jonathan B.

2013-01-01

Polyethylene glycols (PEGs) are widely used to perturb the conformations of nucleic acids, including G-quadruplexes. The mechanism by which PEG alters G-quadruplex conformation is poorly understood. We describe here studies designed to determine how PEG and other co-solutes affect the conformation of the human telomeric quadruplex. Osmotic stress studies using acetonitrile and ethylene glycol show that conversion of the ‘hybrid’ conformation to an all-parallel ‘propeller’ conformation is accompanied by the release of about 17 water molecules per quadruplex and is energetically unfavorable in pure aqueous solutions. Sedimentation velocity experiments show that the propeller form is hydrodynamically larger than hybrid forms, ruling out a crowding mechanism for the conversion by PEG. PEGs do not alter water activity sufficiently to perturb quadruplex hydration by osmotic stress. PEG titration experiments are most consistent with a conformational selection mechanism in which PEG binds more strongly to the propeller conformation, and binding is coupled to the conformational transition between forms. Molecular dynamics simulations show that PEG binding to the propeller form is sterically feasible and energetically favorable. We conclude that PEG does not act by crowding and is a poor mimic of the intranuclear environment, keeping open the question of the physiologically relevant quadruplex conformation. PMID:23804761

Percutaneous Endoscopic Gastrostomy Tube Is a Negative Prognostic Factor for Recurrent/Metastatic Head and Neck Cancer.

PubMed

Siano, Marco; Jarisch, Nadine; Joerger, Markus; Espeli, Vittoria

2018-06-01

Recurrent/metastatic head and neck squamous cell cancer (r/mHNSCC) patients often need a percutaneous endoscopic gastrostomy feeding tube (PEG). Among known prognostic factors, PEG could be prognostic as well. We retrospectively analyzed r/mHNSCC patients referred for systemic treatment. Kaplan-Meier and multivariate cox regression models were applied to assess prognostic impact of PEG. One hunderd and ten patients were identified, 42 had a PEG at treatment start. Median survival from start of 1st-line systemic treatment was 8 months (95%CI=6.5-12.0 months), 4.5 months (95%CI=2.5-7.0 months) for patients with PEG and 11.5 months (95%CI=7.5-14.5 months) without PEG (adjusted HR=1.98, p=0.011). Similarly, survival from first recurrence of distant metastases was lower in patients with PEG as compared to patients without (7.5 vs. 15.5 months, adjusted HR=2.60, p<0.001). Presence of PEG feeding tube has an unfavourable prognostic impact on survival in patients with r/mHNSCC. While any causality remains speculative, potential complications should be appreciated before PEG implantation. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Nano Sponges for Drug Delivery and Medicinal Applications

NASA Technical Reports Server (NTRS)

Tour, James M.; Lucente-Schultz, Rebecca; Leonard, Ashley; Kosynkin, Dimitry V.; Price, Brandi Katherine; Hudson, Jared L.; Conyers, Jodie L., Jr.; Moore, Valerie C.; Casscells, S. Ward; Myers, Jeffrey N.;

Drug release patterns and cytotoxicity of PEG-poly(aspartate) block copolymer micelles in cancer cells.

PubMed

Eckman, Allison M; Tsakalozou, Eleftheria; Kang, Nayon Y; Ponta, Andrei; Bae, Younsoo

2012-07-01

To test physicochemical and biological properties of PEG-poly(aspartate) [PEG-p(Asp)] block copolymer micelles entrapping doxorubicin hydrochloride (DOX) through ionic interaction. PEG-p(Asp) was synthesized from 5 kDa PEG and 20 Asp units. Carboxyl groups of p(Asp) were present as benzyl ester [PEG-p(Asp/Bz)], sodium salt [PEG-p(Asp/Na)] or free acid [PEG-p(Asp/H)]. Block copolymers and DOX were mixed at various ratios to prepare polymer micelles, which were subsequently characterized to determine particle size, drug loading and release patterns, and cytotoxicity against prostate (PC3 and DU145) and lung (A549) cancer cell lines. PEG-p(Asp/Bz), Na- and H-micelles entrapped 1.1, 56.8 and 40.6 wt.% of DOX, respectively. Na- and H-micelles (<100 nm) showed time-dependent DOX release at pH 7.4, which was accelerated at pH 5.0. Na-micelles were most stable at pH 7.4, retaining 31.8% of initial DOX for 48 h. Cytotoxicity of Na-micelles was 23.2% (A549), 28.5% (PC3) and 45.9% (DU145) more effective than free DOX. Ionic interaction appeared to entrap DOX efficiently in polymer micelles from PEG-p(Asp) block copolymers. Polymer micelles possessing counter ions (Na) of DOX in the core were the most stable, releasing drugs for prolonged time in a pH-dependent manner, and suppressing cancer cells effectively.

Superparamagnetic iron-oxide nanoparticles mPEG350- and mPEG2000-coated: cell uptake and biocompatibility evaluation.

PubMed

Silva, Adny H; Lima, Enio; Mansilla, Marcelo Vasquez; Zysler, Roberto D; Troiani, Horacio; Pisciotti, Mary Luz Mojica; Locatelli, Claudriana; Benech, Juan C; Oddone, Natalia; Zoldan, Vinícius C; Winter, Evelyn; Pasa, André A; Creczynski-Pasa, Tânia B

2016-05-01

Superparamagnetic iron oxide nanoparticles (SPIONS) were synthesized by thermal decomposition of an organometallic precursor at high temperature and coated with a bi-layer composed of oleic acid and methoxy-polyethylene glycol-phospholipid. The formulations were named SPION-PEG350 and SPION-PEG2000. Transmission electron microscopy, X-ray diffraction and magnetic measurements show that the SPIONs are near-spherical, well-crystalline, and have high saturation magnetization and susceptibility. FTIR spectroscopy identifies the presence of oleic acid and of the conjugates mPEG for each sample. In vitro biocompatibility of SPIONS was investigated using three cell lines; up to 100μg/ml SPION-PEG350 showed non-toxicity, while SPION-PEG2000 showed no signal of toxicity even up to 200μg/ml. The uptake of SPIONS was detected using magnetization measurement, confocal and atomic force microscopy. SPION-PEG2000 presented the highest internalization capacity, which should be correlated with the mPEG chain size. The in vivo results suggested that SPION-PEG2000 administration in mice triggered liver and kidney injury. The potential use of superparamagnetic iron oxide nanoparticles (SPIONS) in the clinical setting have been studied by many researchers. The authors synthesized two types of SPIONS here and investigated the physical properties and biological compatibility. The findings should provide more data on the design of SPIONS for clinical application in the future. Copyright © 2016 Elsevier Inc. All rights reserved.

Water stress-induced modifications of leaf hydraulic architecture in sunflower: co-ordination with gas exchange.

PubMed

Nardini, Andrea; Salleo, Sebastiano

2005-12-01

The hydraulic architecture, water relationships, and gas exchange of leaves of sunflower plants, grown under different levels of water stress, were measured. Plants were either irrigated with tap water (controls) or with PEG600 solutions with osmotic potential of -0.4 and -0.8 MPa (PEG04 and PEG08 plants, respectively). Mature leaves were measured for hydraulic resistance (R(leaf)) before and after making several cuts across minor veins, thus getting the hydraulic resistance of the venation system (R(venation)). R(leaf) was nearly the same in controls and PEG04 plants but it was reduced by about 30% in PEG08 plants. On the contrary, R(venation) was lowest in controls and increased in PEG04 and PEG08 plants as a likely result of reduction in the diameter of the veins' conduits. As a consequence, the contribution of R(venation) to the overall R(leaf) markedly increased from controls to PEG08 plants. Leaf conductance to water vapour (g(L)) was highest in controls and significantly lower in PEG04 and PEG08 plants. Moreover, g(L) was correlated to R(venation) and to leaf water potential (psi(leaf)) with highly significant linear relationships. It is concluded that water stress has an important effect on the hydraulic construction of leaves. This, in turn, might prove to be a crucial factor in plant-water relationships and gas exchange under water stress conditions.