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Microparticle resins as a potential nasal drug delivery system for insulin.

The application of various resins for the nasal delivery of insulin was examined in rabbits. Intranasal administration of human insulin (28 U, 1 mg) mixed with fractionated sodium polystyrene sulfonate powder (an anionic resin with a particle size of 20-45 microns) caused a rapid increase of the plasma insulin level 413.0 +/- 71.7 microU/ml (mean +/- S.D.) after 15 min, while intranasal administration of insulin alone caused little increase. The blood glucose level decreased from 118.8 +/- 18.5 mg/dl to 65.8 +/- 13.8 mg/dl at 45 min after administration. These results were superior to those obtained with the unfractionated resin. Styrene-divinylbenzene copolymer (a nonionic resin; 20-45 microns fraction) showed similar enhancement of nasal insulin absorption. In contrast, polyacrylester (a nonionic resin; 20-45 microns fraction) and cholestyramine (a cationic resin) did not promote insulin absorption. These results suggest that some resins may be useful for nasal delivery of insulin.

Administration, Intranasal↗

Removal of the antibacterial activity of trimethoprim-sulfamethoxazole, ofloxacin and zidovudine by BACTEC resin-containing blood culture medium.

We determined the capacity of BACTEC resin blood culture media NR 16A and NR 17A to remove the antibacterial activity of trimethoprim-sulfamethoxazole, ofloxacin and zidovudine. Simulated blood cultures containing increasing antibiotic concentrations were inoculated with 10(1), 10(3) and 10(5) CFU/ml blood of various bacterial strains and evaluated with the BACTEC infrared growth detection system. The antibiotic concentrations were adjusted to give breakpoint concentration in the added serum volume or in the total volume of the blood culture vials. Recovery rates and time until detection of bacterial growth in resin-media were compared with those in resin-free media. Trimethoprim-sulfamethoxazole and ofloxacin were, similar to piperacillin, inactivated by resins at antibiotic concentrations that were up to ten times higher than those easily achievable in serum. The antimicrobial effect of zidovudine on gram negative bacteria was reduced in resin media at concentrations corresponding to fifteen times the peak serum levels. Growth of P. aeruginosa, but not of S. aureus, E. coli, K. pneumoniae and Salmonella, was delayed in the presence of resins even at subinhibitory antibiotic concentrations when compared with resin-free media.

Bacteremia↗

Affinity capture of a mammalian DNA polymerase beta by inhibitors immobilized to resins used in solid-phase organic synthesis.

The application of resins normally used in solid-phase organic synthesis to the affinity capture of a mammalian DNA polymerase beta (pol beta) is reported. Lithocholic acid (LCA), an inhibitor of pol beta, was immobilized on various solid supports, and the batch affinity purification of pol beta from a mixture of proteins using these LCA-immobilized resins was examined. Of the resins tested, TentaGel was the most effective at purifying pol beta and at resisting nonspecific absorption of proteins. The immobilized LCA recognized pol beta specifically, which resulted in pol beta binding to the resin. Using the LCA-immobilized resin, it was possible to purify pol beta from a mixture of proteins. Furthermore, it was possible to concentrate pol beta from a crude nuclear extract of human T lymphoma Molt4 cells. To facilitate the immobilization of compounds on TentaGel resins, we also designed and prepared photoaffinity beads containing a photoreactive group at the free termini of the TentaGel resin. The pol beta inhibitors LCA, C18-beta-SQDG, and epolactaene were immobilized on the photoaffinity beads by photoreaction. The batch affinity purification of pol beta from a protein mixture could be also achieved with these beads.

Chromatography, Affinity↗

Comparison of resin and solution screening methodologies in combinatorial chemistry and the identification of a 100 nM inhibitor of trypanothione reductase.

Two identical polyamine peptide conjugate libraries were screened against the parasitic enzyme trypanothione reductase. One of these libraries was in a solution format, while the other was resin-based and was used in two resin-based screens (a diminution assay and a direct bead screening). Potent inhibitors (100 nM) of trypanothione reductase were identified both in the solution screen and in the resin-based screens when using the PEGA resin of Meldal. Resin screening of both types failed to work with TentaGel resin. Importantly there was excellent agreement between the solution and resin-based assays, suggesting both methods are reliable for the screening of combinatorial libraries.

Combinatorial Chemistry Techniques↗

Leaching of concrete admixtures containing thiocyanate and resin acids.

There is an increasing concern about the emission of pollutants during the construction and lifetime of buildings. The leaching of concrete admixtures containing thiocyanate and resin acids was studied using standard leaching tests and chemical analysis. Ecotoxicological risk was assessed for each admixture. Thiocyanate leaching from concrete, with a chlorine-free accelerating admixture, was determined by ion chromatography. Of the total amount of thiocyanate added, 6-8% was emitted within 30 d. The thiocyanate diffusion curve indicates a fast dissolution process from the surface layer, followed by a slower continuous diffusion process. Thiocyanate exhibits both acute and chronic toxicity, which makes it of immediate environmental concern. Resin acid leaching from concrete test specimens containing an admixture of air-entraining agents with tall oil was determined by solid-phase extraction, methylation, and GC/MS. Of added resin acids, 10% was emitted over 143 d. The leaching curves for the resin acids indicate a continuous diffusion that is proportional to the square root of time and follows Fick's first law of diffusion. The chemical composition of the resin acids in the leachate demonstrates degradation and rearrangement of the resin acids during diffusion. Resin acids emitted from concrete are of environmental concern because they are persistent and have the ability to bioaccumulate in aquatic organisms.

Animals↗

Adsorption of flavonoids on resins: hesperidin.

Adsorption of hesperidin from aqueous solutions on styrene-divinylbenzene (SDVB) and acrylic resins was investigated at different pH values (1.5-5.5) and temperatures (10-40 degrees C). Adsorption was not affected by pH variation, whereas it increased on increasing temperature for the SDVB resins and remained substantially unchanged for the acrylic ones. The different behavior of the two types of resins was ascribed to the different wetting, because of their hydrophobic or partially hydrophilic properties, respectively. The equilibrium data at 20 degrees C were determined on 13 commercial resins displaying a wide range of surface areas (S(A), 330-1200 m(2)/g) and pore radii (P(R), 20-260 A). Data were well fitted to the Freundlich isotherm, and its parameters were used to compare the adsorption capacity of different resins. The most effective resin is a SDVB copolymer with the largest S(A) (1200 m(2)/g) and an intermediate P(R) (90 A). The Freundlich constants (K(F)) were rationalized in terms of a two parameter equation, including S(A) and P(R) as independent variables. The adsorption constant increased on increasing both S(A) and P(R) for the resins having P(R) </= 90 A; beyond this limit, the contribution of S(A) was predominant and that of P(R) was slightly negative.

Acrylic Resins↗

Syntheses, characterization and application of cross-linked polystyrene-ethyleneglycol acrylate resin (CLPSER) as a novel polymer support for polypeptide syntheses.

Cross-linked polystyrene-ethyleneglycol acrylate resin (CLPSER) was developed for the solid-phase synthesis of peptide by introducing a cross-linker, O,O'-bis(2-acrylamidopropyl)polyethylene glycol(1900) (Acr(2)PEG), into polystyrene. The cross-linker was prepared by treating acryloyl chloride with O,O'-bis(2-aminopropyl) polyethylene glycol(1900) [(NH(2))(2)PEG] in the presence of diisopropylethylamine. The copolymer was prepared either by bulk or inverse suspension copolymerization of Acr(2)PEG(1900) and styrene using sorbitan monolaurate as the suspension stabilizer, and a mixture of ammonium peroxodisulfate and benzoyl peroxide as the radical initiators. The resin was characterized using gel-phase (13)C NMR, infrared (KBr) spectroscopic techniques and the morphological features of the resin were investigated using scanning electron microscopy photographs. CLPSER showed excellent swelling in a broad range of solvents and was found to be chemically inert to various reagents and solvents used in solid-phase peptide synthesis. To demonstrate the usefulness of the new resin in polypeptide synthesis, the support was derivatized with an 'internal reference' amino acid (norleucine) and a handle 4-(4-hydroxymethyl-3-methoxy)butyric acid. The new resin was compared with commercial supports such as Merrifield and Sheppard resins by synthesizing an acyl carrier protein (65-74) fragment under the same experimental conditions. HPLC profiles revealed the high efficiency of the newly developed support. Resin capability in peptide synthesis was further demonstrated by the solid phase synthesis of a 25-residue peptide from the E2/NS1 region hepatitis C viral polyprotein.

Acrylates↗

Resin-enamel bonds made with self-etching primers on ground enamel.

Self-etching primer adhesives have recently been introduced to simplify bonding. However, the fundamental bonding mechanism of self-etching primers to enamel is not yet fully understood. This study aimed to investigate resin-enamel bonds of self-etching primer adhesives on ground enamel. Two self-etching primer adhesives (Clearfil Liner Bond 2 V and Clearfil SE Bond) were used in this study. A total-etch adhesive (One-Step) was used as a control. Resin-enamel beams were subjected to the microtensile bond test. Subsequently, the failure modes of all specimens were quantified using image analysis. Undemineralized and demineralized ultrathin sections of the resin-enamel bonded specimens were examined using transmission electron microscopy. The bond strengths of Clearfil SE Bond (39.8 +/- 11.9 MPa) and One-Step (46.2 +/- 12.7 MPa) were significantly greater than that of Clearfil Liner Bond 2V (30.4 +/- 6.2 MPa). Scanning electron microscopy of the fractured surfaces revealed the failure direction and weakest portion within each bond. Transmission electron microscopy showed a thin hybridized complex of resin in enamel produced by the self-etching primers without the usual micrometer-sized resin tags seen in resin-enamel bonds produced using the total-etch adhesive. The morphological features of the resin-enamel bonds produced by two self-etching primers tested were different from that created with the total-etch adhesive.

Adhesives↗

A comparison between the wear resistance of three types of denture resin to three different dentifrices.

This study compares the abrasive effects of three dentifrices on three different denture base resins, a heat cured acrylic resin, a self cured acrylic resin and a light activated urethane dimethacrylate-based resin. Specimens of the resins were subjected to a regimen of mechanical brushing using measured amounts of paste on standard toothbrushes driven by a reciprocating device. The apparent wear of each specimen was assessed qualitatively using scanning electron microscopy and quantitatively using profilometry and reflex microscopy. The study showed that cleaning pastes play a significant role in the wear of conventional acrylic resins, the relative abrasivity of the dentifrices being substrate related. However, wear was less evident on the light activated urethane dimethacrylate resin. Brushing with water alone produced no detectable wear on any of the specimens.

Acrylic Resins↗

Effects of the solvents on bond strength of resin bonded porcelain.

Clinical trials of porcelain veneers for chairside colour modifications may require the use of a trial resin with various colours of tints. The bond strength effects of four different solvents used for removal of trial resin from etched porcelain specimens were investigated. Fifty-six porcelain specimens were fabricated, flattened by a metallurgically standard method, etched with hydrofluoric acid and silane treated. The specimens were divided into four groups at random. The trial resin material was cleaned with different solvents prior to bonding of a dual cure resin composite button. After bonding the specimens were stored in water at 37 degrees C for 7 days. Shear bond strength results were as follows: acetone (control) group, 12.9+/-2.9 MPa; ethanol group, 15.1+/-4.6 MPa; methanol group, 11.5+/-2.9 MPa; methylene chloride group, 11.3+/-2.4 MPa. No significant differences were measured (ANOVA, P>0.05). The results indicated that the resin-porcelain bond strengths were not affected by the type of solvent used to remove trial resin. This procedure is recommended for clinical cases when resin composite is used for the try-in of etched porcelain bonded restorations.

Acetone↗

Bonding strength between a hard chairside reline resin and a denture base material as influenced by surface treatment.

Direct relining of dentures made with hard chairside reline resins is faster than laboratory-processed reline systems and the patient is not without the prosthesis for the time necessary to perform the laboratory procedures. However, a weak bond between the autopolymerizing acrylic reline resins and the denture base material has been observed. This study evaluated the effect of six different surface treatments on the bond strength between a hard chairside reline acrylic resin and a heat-cured acrylic resin. Specimens of the heat-cured acrylic resin were divided into seven groups. One of these groups remained intact. In the other groups, a 10-mm square section was removed from the centre of each specimen. The bonding surfaces were then treated with (i) methyl methacrylate monomer, (ii) isobutyl methacrylate monomer, (iii) chloroform, (iv) acetone, (v) experimental adhesive and (vi) no surface treatment -- control group. Kooliner acrylic resin was packed into the square sections and polymerized. The bonding strength was evaluated by a three-point loading test. The results were submitted to one-way analysis of variance (ANOVA) followed by a Tukey multiple range test at a 5% level of significance. No significant difference was found between the surface treatment with Lucitone 550 monomer or chloroform, but both were stronger than the majority of the other groups. The bond strength provided by all the surface treatments was lower than that of the intact heat-cured resin.

Acetone↗

Effect of surface preparation using ethyl acetate on the repair strength of denture base resin.

OBJECTIVE: The objective of this study was to evaluate the effect of surface preparation using ethyl acetate on the repair strength of a denture base resin. MATERIAL AND METHODS: Bar specimens were fabricated with a heat-processed denture base resin and cut in half. The repair surfaces of the specimens were treated with ethyl acetate for varying amounts of time before the autopolymerizing repair resin was applied. The specimens were then immersed in 37 degrees C distilled water for 2 days. A three-point bending test was used to determine the transverse strength of the test specimens. Ten specimens prepared using a 120-s application of ethyl acetate and 10 specimens prepared using a 5-s application of dichloromethane were thermocycled at 10,000 cycles (at 5 degrees C and 55 degrees C) with a 60-s dwell time. The morphological changes in the repair surfaces after preparation were observed by scanning electron microscopy. RESULTS: The repair strength of the denture base resin prepared using ethyl acetate for 120 s (30.6 MPa) was the highest among the results for the various amounts of time tested (p<0.05). There were no significant differences between the repair bond strength both before and after thermocycling of the denture base resin prepared using ethyl acetate for 120 s and that of the denture base resin prepared with dichloromethane for 5 s (p>0.05). CONCLUSION: Within the limitations of the current study, a 120-s application of ethyl acetate was as effective as a 5-s application of dichloromethane at preparing the surfaces of a denture base resin.

Acetates↗

Purine nucleoside phosphorylase: purification using an ether-linked formycin B/sepharose 6B resin with unusual properties.

Formycin B [9-deazainosine] was reacted with epoxy-activated Sepharose 6B to form an affinity resin for purine nucleoside phosphorylase (PNPase). This resin had a large capacity (7,600 units/ml) for the enzyme from Escherichia coli. Enzyme retention was dependent on high ionic strength. Although this property is reminiscent of hydrophobic interaction chromatography, analogous resins prepared with pseudouridine or monoethanolamine instead of with formycin B, did not retain the enzyme even at high ionic strength. Furthermore, hypoxanthine facilitatted elution of the enzyme from the resin. It appeared, therefore, that the enzyme was not bound simply by hydrophobic interactions. A simple two-step purification procedure for PNPase from Escherichia coli was devised using this resin. Overall recovery was 50%, and purity of the final preparation was greater than 95%. This resin was also useful in the purification of PNPase from human erythrocytes. The ether linkage between formycin B and Sepharose 6B, together with the carbon-to-carbon linkage between the pentose and heterocyclic moieties of formycin B, provided stability to both chemical and enzymatic degradation. After 5 years of use and exposure to a variety of biological preparations, the resin showed no detectable decrease in its ability to bind PNPase.

Electrophoresis, Polyacrylamide Gel↗

Examination of styrene-divinylbenzene ion-exchange resins, used in contact with food, for potential migrants.

The nature of extractable substances from five types of styrene-divinylbenzene ion-exchange resins used in the preparation of foodstuffs was investigated. Strong acid cation resins, strong and weak base anion resins, and an active carbon replacement resin were examined. These resins are used for a variety of purposes including water softening, decalcification of sugar syrups, demineralization, removal of nitrate ions from water and decolourization. Analysis was carried out using electrospray LC-MS- and GC-MS-based methodologies. Extractable substances from new resins were identified as mainly being by-products of the resin manufacturing process. Levels of extractable substances decreased with washing.

Chromatography, Liquid↗

Microencapsulation of chlorpheniramine maleate-resin particles with crosslinked chitosan for sustained release.

Formulation and preparation parameters of drug/ion-exchange particles microencapsulated in cross-linked chitosan were evaluated for controlled release of the water-soluble drug chlorpheniramine maleate (CPM) in a suspension. An emulsion solvent evaporation method was used to produce CPM-resinates embedded in glutaraldehyde (GTA) crosslinked chitosan microspheres (MCSs). Crosslinking extent in the chitosan was monitored by swelling measurements. Controlled release was evaluated by dissolution tests in simulated gastric fluid without enzyme (SGF) and in simulated intestinal fluid without enzyme (SIF). CPM-resinates contained 62% (w/w) of drug. MCSs were spherical, ranging from 82 to 420 microns in diameter, and contained multiple resinates. The sizes of MCSs prepared with safflower oil and Span 80 were controlled by surfactant concentration, stirring speed, and duration of stirring. Maximum crosslinking was produced with 240 mg GTA per 250 mg of chitosan. Maximum drug release from free CPM-resinates was about 60% by 1 hr in SGF, and was about 100% by 3 hr in SIF. CPM release was slower from MCSs crosslinked with 120 mg of GTA compared to 5 mg GTA in both media. By 8.3 hr, the more crosslinked MCSs released about 30% CPM in SGF, and about 60% in SIF. Because of the apparent ceiling on release in SGF, the final experiments were conducted in SIF. Increasing the weight ratio of the chitosan coating to CPM-resinate ratio from 1:1 to 4:1 moderately decreased release profiles carried out to 33 hr. Increasing MCS diameters from 82 to 163 microns moderately decreased release profiles. Microencapsulation of CPM-resinates with crosslinked chitosan demonstrated controlled release of CPM in SGF and SIF without enzymes. The retardation effect increased when the crosslinking extent and chitosan to resin ratio increased.

Chitin↗

Photolysis and biodegradation of selected resin acids in River Saale water, Germany.

The River Saale is the Elbe's major tributary flowing through the state of Thuringia, Germany and receives organics inputs from several industrial facilities including pulp and paper mills. Resin acids constitute a major class of polar organics and environmental toxins derived primarily from pulp and paper processing of softwoods. Since wastewater treatment methods at pulp and paper mills are not always capable of removing the persistent resin acids prior to effluent discharge, alternative or complementary degradation methods may be required. Here, the facile photodegradation of four resin acids--abietic, dehydroabietic, isopimaric, and pimaric--was observed with pseudo-first-order kinetics when exposed to broad band and UV254-radiation. Further experimentation in rotating annular biofilm reactors with UV-exposed and unexposed River Saale water spiked with abietic and dehydroabietic acids indicated that photolysis is an effective pretreatment method for resin acid biodegradation. The bacterial toxicity of the aqueous resin acids solutions as measured with Microtox luminescence assays decreased with exposure time. Consequently, photo- and biodegradation of the resin acids did not generate any notable amounts of toxic intermediates and/or the intermediates formed were further degraded into compounds of lower toxicity than the parents. With tandem photo- and biological treatment at pulp and paper mills, as well as in-situ degradation by solar radiation and natural biofilms within the River Saale, resin acid inputs can be reduced in both concentration and toxicity to near undetectable levels with little or no ecological significance.

Acids↗

Chemical analysis of monomers in epoxy resins based on bisphenols F and A.

Diglycidyl ether of bisphenol A (DGEBA) is the monomer and most important contact allergen in epoxy resin(s) based on bisphenol A (DGEBA-R). Both thin-layer chromatography (TLC) and high-pressure liquid chromatography (HPLC) methods are available for the analysis of products containing DGEBA-R. With respect to detection and quantification, epoxy resins of the bisphenol F-type, i.e. epoxy resins containing the isomers of diglycidyl ethers of bisphenol F (DGEBF), are not as well investigated as DGEBA-R. The isomers of DGEBF are p,p'-DGEBF, o,p'-DGEBF and o,o'-DGEBF. Both p,p'-DGEBF and o,p'-DGEBF have been shown to be contact allergens in humans, and all 3 isomers are sensitizers in the guinea pig maximization test. We aimed (i). to develop HPLC methods for separation and purification of the individual DGEBF isomers, (ii). to detect and quantify the DGEBF isomers in epoxy resins of the bisphenol F-type and (iii). to evaluate and develop the TLC as a method for the detection of the DGEBF monomers. We found the total content of the DGEBF isomers in the investigated epoxy resins of the bisphenol F-type to vary from 17.0 to 81.7% w/w. Some of them also contained 0.1-2.4% w/w DGEBA. The HPLC method showed a sensitivity that was 2000-20 000x higher than that obtained with the TLC method for the DGEBF monomers. We concluded that the range of the DGEBF isomer content in epoxy resins of the bisphenol F-type is approximately the same as the monomer content in liquid compared to solid DGEBA-R. The relevance of contact allergy to DGEBA-R can remain unrecognized if the suspected product is an epoxy resin of the bisphenol F-type, which is analysed with the TLC method.

Allergens↗

Preparation of protected peptide amides using the Fmoc chemical protocol. Comparison of resins for solid phase synthesis.

Different resins were examined for their potential use in the solid phase synthesis of protected peptide amides using the 9-fluorenylmethoxycarbonyl (Fmoc) chemical protocol. The model protected peptide amide BocTyr-Gly-Gly-Phe-Leu-Arg(Pmc)NH2 (1) was synthesized on both the acid-labile 4-(2',4'-dimethoxyphenyl-Fmoc-aminomethyl)phenoxy resin (Rink amide resin) (2) and on resins containing the base-labile linker 4-hydroxymethylbenzoic acid. Of the resins examined only the methylbenzhydrylamine resin containing the 4-hydroxymethylbenzoic acid linkage, which was cleaved by ammonolysis in isopropanol, gave the model peptide 1 in good overall yield (53% including functionalization). Thus the synthesis of protected peptide amides by solid phase synthesis using Fmoc-protected amino acids with t-butyl-type side chain protecting groups is feasible. The choice of peptide-resin linkage and its cleavage conditions, however, are critical to the success of such syntheses. The potential application of this synthetic strategy to the preparation of novel peptide amides is discussed.

Amino Acid Sequence↗