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Intestinal absorption of polymeric derivatives of the food dyes sunset yellow and tartrazine in rats.

1. Absorption and metabolism of 14C-labelled sunset yellow (FD & C Yellow No. 6), tartrazine (FD & C Yellow No. 5) and high molecular weight polymeric derivatives of the two azo dyes were compared in rats. 2. A trace to 1.5 percent of unchanged monomeric dyes was excreted in urine and bile during the first 24 h after dosing. No unchanged dye was absorbed after administration of the polymeric derivatives. 3. In animals dosed with sunset yellow and its polymer derivative, absorption of the azo-bound cleavage product 1-amino-2-naphthol-6-sulphonic acid was 8.5 and 6.9 percent, respectively, while absorption of the cleavage product sulphanilic acid was 37.4 and 0 percent, respectively. 4. In animals dosed with tartrazine and its polymer derivative, absorption of the cleavage product aminopyrazolone and its metabolites was 4.0 and 4.6 percent, respectively. 5. Azo bond cleavage did not appear to be decreased in the polymer derivatives. However, the sulphanilic acid moiety of both dyes remained attached to the polymer backbone, resulting in a 95 percent decrease in sulphanilic acid absorption with polymeric tartrazine. 6. Decreased absorption of unchanged dyes and certain metabolites with the stable, non-absorbed polymeric derivatives may be significant in developing non-sensitizing substitutes for these two commonly used food colourants.

Animals↗

Selective delivery of adriamycin to a solid tumor using a polymeric micelle carrier system.

The anticancer drug, adriamycin (ADR), was incorporated by physical entrapment into polymeric micelles for selective delivery to a murine solid tumor colon adenocarcinoma 26 (C 26). In vivo antitumor activity of ADR was greatly enhanced by this incorporation into polymeric micelles. Using one polymeric micelle delivery system, the tumor completely disappeared at two doses, while free ADR exhibited a fair inhibition effect on tumor growth only at the maximum tolerated dose. Biodistribution analysis revealed that the physically entrapped micellar ADR accumulated at tumor sites in a highly selective manner. These results indicate that these polymeric micelles are a promising system for delivering hydrophobic anticancer drugs selectively to solid tumor sites using a passive targeting mechanism.

Adenocarcinoma↗

Cell adhesion to the surfaces of polymeric beads.

The main goal of this study is to determine the relationship between the surface properties of polymeric materials and fibroblastic cell adhesion. Therefore, two series of polymeric beads, PHEMA and PS, were tested in microcarrier-facilitated cell culture systems. The crosslinked PHEMA beads were prepared by suspension polymerization of HEMA monomer in the presence of various acrylic monomers (i.e. MMA, EGDMA, DMAEMA). The hydrophobic PS beads were used after coated with different alkylamine monomers (i.e. EDA, ALAM, TEA) by plasma polymerization process. The cell culturing studies were performed with BHK cells in stationary culture conditions and the cell adhesion characteristics were determined by the common methods. Attachment of the BHK cells on these microcarriers were satisfactorily modeled by surface saturation type of mathematical expression. The results demonstrated that, there were finite number of sites on the microcarrier surfaces available for adhesion. Number of these sites depends on the surface charge density which was supplied by amine groups and surface wettability. It is possible to achieve desired cell adhesion and also growth, by changing the chemical structure of beads with suitable modification methods.

Allylamine↗

Preparation and characterization of crosslinked and polymerized hemoglobin solutions.

In 1982 we synthesized 2-Nor-2-formylpyridoxal 5'-phosphate (NFPLP) and subsequently showed that coupling of the beta chains of hemoglobin (Hb) by this organic phosphate compound according to Benesch et al. (1) lowers the oxygen affinity and prolongs the retention time in the circulation of rats and rabbits with a factor 3 by prevention of excretion via the kidneys. Optimal conditions for the purification of HbNFPLP either by ion-exchange chromatography or by heat treatment were established with recoveries of 70% and 85%, respectively. By extrapolation from the data in rats and rabbits a half life of about 8 hours can be expected in the circulation of humans. However, under some conditions a further prolongation is required. The aim of further modification of HbNFPLP was to achieve a retention time of about 24 hours. Polymerization with glutaraldehyde to polyHbNFPLP resulted in a mixture of polymers of different size. We determined the optimal degree of polymerization with respect to the effects on vascular retention time, oncotic activity, viscosity and oxygen affinity. Depending on the degree of polymerization we found in rats a 5- to 7- fold increase in vascular half-life compared to native Hb. The change in oxygen affinity was found to be independent of the polymer size (P50 = 18-22 mmHg). A limiting factor for polymerization is the increase in viscosity, which was dramatic when large polymers (greater than 300 kD) were present in the preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Synthesis and properties of polymerized, diaspirin cross-linked hemoglobins.

During the course of our studies it became clear that there were therapeutic applications for which a polymeric hemoglobin having an extended half-life in circulation would be appropriate. Therefore, a process for the glutaraldehyde-polymerization of diaspirin cross-linked hemoglobin (DCLHb) was developed and used to prepare glutaraldehyde-polymerized DCLHb (GP-DCLHb) in lactated Ringer's solution in sufficient quantities for biological testing. Both isovolemic exchange-transfusion and "top-load" studies (rats; primates and swine, respectively) were completed in which a broad spectrum of physiologic, histopathologic and analytical parameters were monitored and assessed. In general, GP-DCLHb in lactated Ringer's solution was well-tolerated physiologically. When compared to DCLHb, GP-DCLHb offers the advantages of reduced renal clearance of hemoglobin and an extended half-life in circulation. GP-DCLHb has the disadvantages that (1) glutaraldehyde is an ineffective virucidal agent under the conditions of the polymerization reaction and a separate virus inactivation step is required; (2) low-endotoxin (LAL-negative) GP-DCLHb solutions are pyrogenic (rabbits); and (3) unusual deposition of hemoglobin-containing material in the small arterioles of the liver and kidney (rats) was sometimes seen even after a period of time (2 weeks) during which treatment-related organ pathologies are usually resolved, a finding peculiar to GP-DCLHb among the various hemoglobin derivatives we have tested.

Animals↗

Effect of polymerization on clearance and degradation of free hemoglobin.

In the present study we investigated the mechanism of prolongation of the plasma retention of free hemoglobin by polymerization. Polymerization of intramolecularly crosslinked hemoglobin with glutaraldehyde yields a mixture of large polymers, small polymers and monomers. In exchange transfusion experiments in rats we analyzed plasma samples by gel filtration to determine the clearance of polymers of different size. A positive correlation was found between polymer size and vascular retention. Furthermore, the clearance of large polymers appeared to be highly dose-dependent: after 20% and 70% exchange transfusions, we observed for large polymers a plasma half-life of 12 and 26 hours, respectively, whereas the half-life for 64 kD monomers was 4 hours in both cases. The degradation of hemoglobin was followed by measuring the bilirubin excretion. The infused heme was recovered as bilirubin within 72 hours. The delay between the disappearance of free hemoglobin from the plasma and the recovery as bilirubin was about six hours and was not affected by polymerization or dose. We conclude that polymerization prevents the operation of certain clearance mechanisms, while still allowing a route of clearance that is easily saturated. The intracellular degradation of heme into bilirubin is not affected by the modifications of hemoglobin and is not easily saturated.

Animals↗

A comparison of rates of heme exchange: site-specifically cross-linked versus polymerized human hemoglobins.

The stability of the heme-globin interaction of chemically modified human hemoglobin (Hb) was tested by measuring rates of heme loss from methemoglobin. Heme transfer from methemoglobin to human serum albumin was measured by rapid-scanning spectrophotometry, and the resulting absorption matrices were analyzed by singular value decomposition. Unmodified human HbA0, hemoglobin cross-linked between beta subunits with either 2-nor-2-formylpyridoxal 5'-phosphate or 3,5-(dibromosalicyl)fumarate (DBBF), hemoglobin cross-linked between alpha subunits with DBBF, and pyridoxalated hemoglobin polymerized with either glycolaldehyde or glutaraldehyde were tested. Initial rates were evaluated by fitting the time courses to a biexponential equation using a matrix least squares curve-fitting algorithm. Reaction rates fell into two classes: (1) HbA0 and the site-specifically cross-linked hemoglobins, with biphasic rates of heme loss of 0.02 and 0.004 min-1, and (2) polymerized hemoglobins, with 10-20-fold higher rates at 0.5 and 0.03 min-1. The total fitted amplitudes of the reaction depended upon the specific modification: beta beta-cross-linked Hbs < alpha alpha-cross-linked Hb approximately glycolaldehyde polymerized Hb < glutaraldehyde polymerized Hb < HbA0.

Blood Substitutes↗

Effects of polymerization heat and monomers from acrylic cement on canine bone.

We investigated the effects of polymerization heat and toxicity of polymethylmetacrylate bone cement in the canine tibial diaphysis. Heat was studied by filling the tibias with either bone cement or bone wax contained in a monomer tight membrane pouch. Toxicity was studied by filling both tibias with cement, with the control side contained in the membrane pouch. Bone blood perfusion was measured by microsphere technic, and bone remodeling by 99mTc-methylene diphosphonate uptake and by histologic technique. In bone exposed to the combination of polymerization heat and monomer, both perfusion and remodeling were impaired. We did not find any effects of polymerization heat alone. We conclude that hot toxic chemicals from bone cement during polymerization may inhibit bone blood perfusion and remodeling, whereas heat alone seems to be of minor importance for the regenerative processes in cemented diaphyseal bone.

Animals↗

Polymerization shrinkage and contraction force of composite resin restorative inserted with "Megafiller".

This study quantified the contraction force and polymerization shrinkage of composite resins with/without beta-Quartz Glass Ceramic Inserts (BQCI) as "Megafiller". The materials used for the determination included a chemically cured composite and five light-cured composites. The system for measuring contraction force consisted of a transparent teflon tube for preparing the specimen, a small load cell, a dynamic strain gauge and a pen-recorder. After the composite was packed into the teflon mold, a BQCI (Type R3) was inserted through the opening and the specimen was cured. Linear polymerization shrinkage of the composites was measured every 10 seconds from the start of mixing or irradiation to 90 minutes by the mercury bath method. Three pieces each of BQCI (Type T3) were inserted in each specimen. The results suggested that BQCI was markedly effective in reducing polymerization shrinkage, but was not always effective in reducing the contraction force during polymerization.

Acrylic Resins↗

Thermal- and photo-polymerization of (meth) acrylates containing a spiro ortho ester moiety and the properties of poly[(meth)acrylate]s.

The syntheses and polymerizations of acrylate (ASOE) and methacrylate (MASOE) containing spiro ortho ester moieties were carried out and the properties of the polymers obtained were investigated. The ring-opening reaction of the spiro ortho ester groups proceeded well during heat polymerization (HC) with the ionic initiators (BSS and HPSS). However, a small amount of unreacted carbon-carbon double bond was observed in the polymers obtained. Not only vinyl polymerization but also a small amount of ring-opening reaction took place during polymerization with radical initiators (BPO, AIBN, DTB and CQ). The poly-(MASOE)s obtained by HC with BSS, BSS/AIBN and BSS/BPO were plastic like polymers. Low volume shrinkage was observed during HC and UVLC of ASOE and MASOE with ionic initiators. These shrinkages were smaller than those of conventional methacrylate.

Acrylates↗

Effect of light wavelength on polymerization of light-cured resins.

Experimental light-cured composite resins were exposed to a narrow-band light at a constant quantum number using a narrow-band interference filter. The IR spectra of the cured resin specimens were measured before and after extraction of residual monomers. Degree of conversion (DC) and polymerization conversion (PC) were calculated from these IR spectra. The light in 410-550 nm could be polymerized. With a brief exposure (5 s), DC and PC were affected by the wavelength. The effect of wavelength between 410 and 490 nm decreased with increasing duration of exposure. The most efficient wavelength was 470 nm and the most adequate wavelength was in the 450-490 nm wavelength range. The absorbance of camphorquinone strongly affected polymerization, especially during the initial stage. However, from the relationship between DC or PC and exposure energy, polymerization depended not only on the wavelength of the light, but also on the exposure energy.

Bisphenol A-Glycidyl Methacrylate↗

Studies on MMA-tBB resin. I. Comparison of TBB and other initiators in the polymerization of PMMA/MMA resin.

Polymerization characteristics of poly (methyl methacrylate)(PMMA)/(methyl methacrylate) (MMA) resin initiated by tributylborane (TBB) were compared with those by benzoyl peroxide (BPO)/N,N-dimethyl-p-toluidine and camphorquinone (CQ)/N,N-dimethylaminoethyl methacrylate from the aspects of temporal changes of residual MMA and molecular weight up to 4 weeks at 37 degrees C. Residual MMA 30 min after polymerization decreased from 8.15% for TBB resin, 8.39% for the BPO resin, and 9.19% for the CQ resin to 0.48%, 3.54%, and 6.79%, respectively, after 4 weeks. The molecular weights at 30 min and 4 weeks after polymerization were 409 x 10(3) and 247 x 10(3) for TBB resin, 297 x 10(3) and 282 x 10(3) for the BPO resin, and 267 x 10(3) and 231 x 10(3) for the CQ resin, respectively. The present results revealed that the TBB-initiated polymerization had unique and different characteristics compared with those initiated by the other common initiators: (1) The decrease in residual MMA was fast, sustained for a long time and resulted in very low value; (2) high molecular weight PMMA was formed first and then decreased with time.

Analysis of Variance↗

Dimensional accuracy of acrylic resin maxillary denture base polymerized by a new injection pressing method.

The purpose of this study was to confirm the dimensional accuracy of a newly developed injection pressing method for resin polymerization by making use of the internal electric resistance of resin to determine the optimal timing for resin injection. A new injection pressing polymerization pot with a built-in system to measure the internal electric resistance of resin was used for resin polymerization. Fluid-type resin was injected into the mold of a maxillary complete denture base under nine different conditions: three different timings for resin injection according to the electric resistance of resin dough (early stage: 11 Mohms; intermediate stage: 16 Mohms; final stage: 21 Mohms) and three different motor powers for resin injection (2000 N, 4000 N, and 6000 N). In the best polymerization condition (injected during the early stage of resin dough under a motor power of 6000 N), the adaptation of the denture base showed a statistically significant improvement compared with the conventional pouring method.

Acrylic Resins↗

Bonding properties of heat-polymerized denture base resin to Ti-6Al-7Nb alloy.

The purpose of this study was to evaluate the shear bonding strength and leakage of heat-polymerized denture base resin to titanium-aluminum-niobium (Ti-6Al-7Nb) and cobalt-chromium (Co-Cr) castings using four adhesive systems; three adhesive primers (Metal Primer II, Metal Link, MR. Bond) and one heat-polymerized adhesive resin containing 4-META (Metadent). The resin tab was heat-polymerized directly with or without the primer. Shear bonding strengths and dye penetration distances were determined before and after 10,000 times of thermocycling. The results were analyzed with three-way ANOVA and Tukey's comparison (p<0.05). Thermocycling significantly decreased bonding strength and promoted dye penetration. However, with the application of adhesive systems, post-thermocycling bond strength was significantly improved and dye penetration was inhibited. The bonding strength of Ti-6Al-7Nb was significantly smaller than that of Co-Cr, but the difference was marginal. These results suggested that the examined adhesive systems significantly improved the bonding efficiency of heat-polymerized resin to Ti-6Al-7Nb and Co-Cr alloys.

Acrylic Resins↗

Short report: floxacrine analog WR 243251 inhibits hematin polymerization.

Floxacrine was a promising antimalarial compound that led to the identification of WR 243251. On the basis of their structures, we suspected that these compounds might be good inhibitors of hematin polymerization. Indeed, WR 243251 was as potent and floxacrine was only 2-fold less potent than chloroquine as inhibitors of this process. However, this hematin polymerization inhibition did not completely account for the increased antimalarial potency of WR 243251 versus chloroquine. The WR 243251 ketone hydrolysis product WR 243246 was without activity against hematin polymerization. These data also confirm that hematin polymerization inhibition can be quite sensitive to small changes in inhibitor structure.

Acridines↗

Fibrinogen Matsumoto III: a variant with gamma275 Arg-->Cys (CGC-->TGC)--comparison of fibrin polymerization properties with those of Matsumoto I (gamma364 Asp-->His) and Matsumoto II (gamma308 Asn-->Lys).

Fibrinogen Matsumoto III (M-III) is a dysfibrinogen identified in a 66-year-old woman with rectal cancer. The fibrinogen level determined by the thrombin-time method was markedly decreased in preoperative coagulation tests of her plasma. Three fibrinogen polypeptide-chain gene fragments from the proposita were amplified by the polymerase chain reaction method, then sequenced. The triplet CGC encoding the amino acid residue gamma275 was replaced by TGC, resulting in the substitution of Arg->Cys. There have been previous reports of nine families with the same alteration, nine families with an Arg->His variant and one family with an Arg->Ser variant in this residue, which has been shown to be one of the most important amino acids in the 'D:D' interaction site. In addition, there are three silent mutations in the Aalpha-chain gene and two mutations in the intron of the Bbeta-chain and the gamma-chain gene. However, none of these mutations is thought to be the cause of the dysfunctional fibrinogen. The thrombin-catalyzed fibrin polymerization in the presence of 1 mM Ca ions was markedly delayed in purified M-III. Its lag period was longer than those of Matsumoto II (M-II; gamma308Asn->Lys) and Matsumoto I (M-I; gamma364Asp-His). gamma364Asp is one of the most important residues in the polymerization pocket of the 'D:E' interaction site and gamma308Asn is located in the vicinity of a high affinity Ca2+ binding site in the D-domain, gamma311-336. The maximum slope of the polymerization curve for M-III was about 4-fold steeper than that for M-1 but less steep than that for M-II. These results may suggest that the tertiary structure of the polymerization pocket plays a more important role in the lateral aggregation of protofibrils than that of the 'D:D' interaction site.

Aged↗

[Inhibition of polymerization by oxygen in composite filling materials and enamel sealers].

The oxygen inhibition upon the polymerization of composite materials was investigated. The method permitted the avoidance of oxygen inhibition even in cases where the special matrix could not be used. The results can be summarized as follows: 1. The depth of inhibition, when atmospheric air is admitted, varies, according to different brands of composites, between 25 and 105 mum. 2. By conducting a protective gas over the surface of the polymerizing material, the contact of oxygen is avoided just as if a matrix were used. 3. Avoidance of oxygen is particularly important during the setting period of the material, i.e. the time between the end of mixing and the end of setting. 4. Polymerization under a protective gas makes it possible to polymerize even very thin layers of material and therefore widens the scope of use for sealants in caries prophylaxis.

Dental Materials↗

Characterization of polymeric buffers for operating membrane-trapped enzyme reactors in an electric field.

A novel class of amphoteric, polymeric buffers, is described, consisting of grafting onto growing polyacrylamide chains weakly acidic and basic acrylamido-monomers (called Immobilines; protolytic groups as N-substituents on the nitrogen of the amido bond), for operating a membrane-immobilized enzyme reactor (MIER) in an electric field. With these soluble, polymeric buffers, it is possible to operate the membrane reactor at any optimum of pH activity, for any given enzyme, in the pH 3-10 scale. Such buffers, being amphoteric, are confined in the enzyme reaction chamber by the same isoelectric trapping mechanism. The best buffers were found to be those polymerized in presence of 9% neutral monomer (acrylamide) and containing 20 mM Immobiline as buffering ion. To decrease their viscosity in solution, the polymeric buffers are synthesized at high temperatures (70 degrees C) and in presence of a chain-transfer agent. The weight average molecular size in these conditions has been found to be ca. 200,000 Da. These buffers exhibited excellent performance in a variety of enzyme reactions in the MIER, such as in the case of penicillin G acylase and histidine decarboxylase and were found to greatly stabilize enzyme activity, permitting operation of the MIER over extended periods of time. As an example, in a penicillin G acylase reactor, >75% enzyme activity was maintained over a 10-d cycle of operation, while with conventional buffers more than 90% inactivation was experienced over the same period of time. This novel class of macromolecular, amphoteric buffers could also be exploited in other types of conventional bioreactors not based on an isoelectric trapping mechanism.

Bioreactors↗