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Mechanochemical solid-state polymerization. VIII. Novel composite polymeric prodrugs prepared by mechanochemical polymerization in the presence of pharmaceutical aids.

We carried out the mechanochemical polymerization of methacryloyl derivatives of acetoaminophen and 5-fluorouracil in the presence of lactose. The reaction proceeded readily and the polymeric prodrugs were quantitatively produced. This method produces powdered polymeric prodrugs in which fine particles of lactose are homogeneously dispersed, since the reaction proceeds quantitatively through a totally dry process. It is difficult to prepare such a powdered polymeric prodrug by conventional solution polymerization. The rate of drug release of polymeric prodrugs increases with increasing content of lactose, as is shown to be true of the specific surface of polymeric prodrugs. These results suggest that lactose is homogeneously dispersed in powdered polymeric prodrugs. The present method seems applicable to a wide variety of pharmaceutical aids. If one takes the physiochemical property of pharmaceutical aids into consideration, novel polymeric prodrugs with a variety of drug release rates can be synthesized simultaneously with mixing.

Acetaminophen↗

The polymerization of actin: extent of polymerization under pressure, volume change of polymerization, and relaxation after temperature jumps.

The protein actin can polymerize from monomeric globular G-actin to polymeric filamentary F-actin, under the regulation of thermodynamic variables such as temperature, pressure, and compositions of G-actin and salts. We present here new measurements of the extent of polymerization (phi) of actin under pressure (P), for rabbit skeletal muscle actin in H2O buffer in the presence of adenosine triposphate and calcium ions and at low (5-15 mM) KCl concentrations. We measured phi using pyrene-labeled actin, as a function of time (t) and temperature (T), for samples of fixed concentrations of initial G-actin and KCl and at fixed pressure. The phi(T,P) measurements at equilibrium have the same form as reported previously at 1 atm: low levels of polymerization at low temperatures, representing dimerization of the actin; an increase in phi at the polymerization temperature (Tp); a maximum in phi(T) above Tp) with a decrease in phi(T) beyond the maximum, indicating a depolymerization at higher T. From phi(T,P) at temperatures below Tp, we estimate the change in volume for the dimerization of actin, DeltaVdim, to be -307+/-10 ml/mol at 279 K. The change of Tp with pressure dTp/dP=(0.3015+/-0.0009) K/MPa=(30.15+/-0.09) mK/atm. The phi(T,P) data at higher T indicate the change in volume on propagation, DeltaVprop, to be +401+/-48 ml/mol at 301 K. The phi(t) measurements yield initial relaxation times rp(T) that reflect the behavior of phi(T) and support the presence of a depolymerization temperature. We also measured the density of polymerizing actin with a vibrating tube density meter, the results of which confirm that the data from this instrument are affected by viscosity changes and can be erroneous.

Actins↗

Influence of polymerization mode of dual-polymerized resin direct core foundation systems on bond strengths to bovine dentin.

STATEMENT OF PROBLEM: Little is known about how various polymerization combinations of dual-polymerized adhesives and resin core foundation pastes affect dentin bond strength. PURPOSE: This study examined the influence of different polymerization modes of dual-polymerized resin direct core foundation systems on dentin bond strength using bovine dentin. MATERIAL AND METHODS: Two commercially available dual-polymerized resin direct core foundation systems, Clearfil DC Core and UniFil Core, were studied. Bovine mandibular incisors were mounted in autopolymerizing resin and the facial dentin surfaces were ground wet on 600-grit SiC paper. Dentin surfaces were treated according to manufacturer's recommendations, and dual-polymerized adhesives were applied and dual-polymerized (control) or only chemically polymerized. The core foundation resins were condensed into the mold (4 x 2-mm) and were also either dual-polymerized or only chemically polymerized. Eighty specimens (n=10) were stored in 37 degrees C water for 24 hours, then shear tested at a crosshead speed of 1.0 mm/min in a universal testing machine. Fourier transformation infrared spectroscopy was used to measure the degree of conversion of dual-polymerized resin core foundation pastes with both modes of polymerization. One- and 2-way ANOVA, Tukey HSD tests, and Student t -tests were performed (alpha=.05). RESULTS: The highest mean bond strengths (+/-SD) were obtained when the adhesives and resin pastes were dual-polymerized for both core foundation systems (14.6 +/- 2.1 MPa for Clearfil DC Core, 15.6 +/- 2.2 MPa for UniFil Core). Chemical polymerization of dual-polymerized adhesives and resin pastes resulted in significantly lower bond strength (2.8 +/- 0.6 MPa for Clearfil DC Core, 8.1 +/- 2.2 MPa for UniFil Core) ( P <.001). The degree of conversion for the resin pastes decreased significantly ( P <.05) when only chemical polymerization was employed, from 81.5% to 76.1% for Clearfil DC Core and 86.7% to 81.2% for UniFil Core. CONCLUSION: The data suggests that the dentin bond strengths of the dual-polymerized resin direct core foundation systems are highest when both adhesive and resin core paste are dual polymerized.

Analysis of Variance↗

Polymerization rate and mechanism of ultrasonically initiated emulsion polymerization of n-butyl acrylate.

The factors affecting the induction period and polymerization rate in ultrasonically initiated emulsion polymerization of n-butyl acrylate (BA) were investigated. The induction period takes only an instant in ultrasonically initiated emulsion polymerization of BA without any added initiator by enhancing the N2 flow rate. Increasing temperature, power output and SDS concentration, decreasing the monomer concentration results in further decreasing induction period and enhanced polymerization rate. Under optimized reaction conditions the conversion of BA reaches 92% in 11 min. The polymerization rate can be controlled by varying reaction parameters. The apparatus of ultrasonically initiated semi-continuous and continuous emulsion polymerization were set up and the feasibility was first studied. Based on the experimental results, a free radical polymerization mechanism for ultrasonically initiated emulsion polymerization was proposed, including the sources of the radicals, the process of radical formation, the locus of polymerization and the polymerization process. Compared with conventional emulsion polymerization, where the radicals come from thermal decomposition of a chemical initiator, ultrasonically initiated emulsion polymerization has attractive features such as no need for a chemical initiator, lower reaction temperature, faster polymerization rate, and higher molecular weight of the polymer prepared.

Journal Article↗

Effect of high-powered LED polymerization on the shear bond strength of a light-polymerized resin luting agent to ceramic and dentin.

STATEMENT OF PROBLEM: A newly introduced high-powered light-emitting diode (LED) light-polymerization unit with various polymerization modes is purported to polymerize dental resins more quickly than standard units. However, there is insufficient information about the effects of this type of light source and its polymerization modes on resin luting agents (RLAs). PURPOSE: This in vitro study evaluated the effects of different modes of a high-powered LED polymerization unit on the shear bond strength of a light-polymerized RLA to ceramic and dentin. MATERIAL AND METHODS: Sixty ceramic cylinders (3 x 3 mm) were fabricated from a heat-pressed ceramic (IPS Empress 2). Specimen surfaces were abraded using 600-grit silicon carbide paper and airborne-particle abraded with 50-mum desiccant alumina particles, cleaned ultrasonically, etched using hydrofluoric acid, and treated with a silane coupling agent (Ceramic primer). Sixty noncarious, freshly extracted, permanent human molar teeth were embedded in autopolymerizing acrylic resin, and their dentin surfaces were wet-ground using a grinding and polishing machine fitted with 180-grit abrasive disks. The ground dentin surfaces were then etched with 37% phosphoric acid gel, and an adhesive agent (Single Bond) was applied. Ceramic specimens (n = 15) were bonded to dentin surfaces with a dual-initiated RLA (Rely-X ARC) and individually polymerized by 1 of 4 different modes, as follows: Halogen standard mode (Control) (600 mW/cm2 for 40 seconds); high-powered LED fast mode (1100 mW/cm2 for 10 seconds); high-powered LED pulse mode (1100 mW/cm2 for 10 seconds); and high-powered LED exponential mode (1100 mW/cm2 for 20 seconds). Cemented specimens were subjected to shear loading until fracture using a universal testing machine. A stereomicroscope (x25) was used to identify the mode of fracture. Bond strength (MPa) data were analyzed using 1-way analysis of variance and the Tukey HSD test (alpha = .05). RESULTS: Specimens polymerized using halogen standard mode (23.9 +/- 1.3 MPa) and LED exponential mode (23.0 +/- 1.1 MPa) had significantly higher ( P < .001) mean shear bond strengths compared with both LED fast (15.1 +/- 1.3 MPa) and pulse (14.6 +/- 1.3 MPa) modes. The Tukey HSD tests showed no significant differences in shear bond strength between specimens polymerized using high-powered LED exponential mode and halogen standard mode. Most failures were adhesive failures at the dentin-RLA interface or the RLA-ceramic interface in specimens polymerized using high-powered LED fast or pulse modes. CONCLUSION: Within the limitations of this study, the shear bond strength of an RLA to ceramic and dentin was found to be similar when polymerized using halogen light in standard mode and high-powered LED light in exponential mode, whereas shear bond strength was significantly lower when polymerized using LED in fast or pulse mode.

Analysis of Variance↗

[A design and development of novel polymeric prodrugs prepared by mechanochemical solid-state polymerization].

The mechanochemical polymerization of solid-state monomer was first reported in 1959. Nevertheless, relatively little work has been done. We reported the first in-depth study of the mechanochemical polymerization of specially synthesized solid-state monomers, methacryloyl derivatives of bioactive compounds including detailed mechanistic implications. There are many advantages for this reaction. One of the most striking properties observed in the resulting polymers is that these polymeric prodrugs are of very low heterogeneity (narrow molecular weight distribution) which is of great value in pharmaceuticals for highly functionalized polymeric prodrugs. Thus, the present reaction provides a novel and simple methodology for the syntheses of highly functionalized polymeric prodrugs through a totally dry process. The nature of drug release from many kinds of polymeric prodrugs prepared by mechanochemical polymerization was also investigated. The rate of drug release from the polymeric prodrugs can be controlled by the property of comonomer and the structure of spacer between the main chain of polymer and drug. Several applications of polymeric prodrugs (chemoembolization and hybrid polymeric prodrugs) were also described. We have carried out the mechanochemical polymerization in the presence of pharmaceutical aids to exploit the features of this reaction. If one takes the physicochemical property of pharmaceutical aids into consideration, novel composite polymeric prodrugs possessing a variety of rates of drug release can be synthesized simultaneously with mixing.

Chemical Phenomena↗

Chronic inhalation toxicity and carcinogenicity study of respirable polymeric methylene diphenyl diisocyanate (polymeric MDI) aerosol in rats.

Four groups of 60 Wistar rats of each sex were exposed by inhalation to 0, 0.2, 1.0, or 6.0 mg/m3 respirable polymeric methylene diphenyl diisocyanate (polymeric MDI) aerosol (93.5% < 4.2 microns) for 6 hr a day, 5 days a week for up to 24 months. In addition, satellite groups of 10 rats/sex/group received the same treatment for 12 months. There was no adverse effect on general health, survival, body weight, or hematological or clinical chemistry parameters. Lung weights were increased in both males and females exposed to 6.0 mg polymeric MDI/m3 for 12 or 24 months. Gross examination at autopsy of males exposed to 6.0 mg polymeric MDI/m3 for 24 months revealed an increased incidence of spotted and discolored lungs. Increased incidences of degeneration and basal cell hyperplasia of the nasal olfactory epithelium, often accompanied by hyperplasia of Bowman's glands, were found in the 1.0 and 6.0 mg/m3 groups. Light and electron microscopic studies of the lungs revealed accumulations of alveolar macrophages containing polymeric MDI-associated refractile yellowish material at the level of the alveolar duct in all exposed groups. Alveolar duct epithelialization as well as fibrosis of tissues surrounding the macrophage accumulations occurred at the 1.0 and 6.0 mg/m3 exposure levels. In addition, increased incidences of calcareous deposits and localized alveolar bronchiolization were seen in the 6.0 mg/m3 group. Moreover, eight pulmonary adenomas (six in males and two in females) and one pulmonary adenocarcinoma (in a male) were observed in the 6.0 mg/m3 exposure group. The time sequence of the spectrum of pulmonary changes indicates that recurrent alveolar wall damage by polymeric MDI and/or polymeric MDI-containing alveolar macrophages leads to alveolar bronchiolization and ultimately to bronchioloalveolar tumors. No lung tumors were found in the lower concentration groups and in the control group. The incidence and distribution of other types of tumors were not influenced by polymeric MDI. It was concluded that in the present study, the "no-observed-adverse-effect level" of polymeric MDI was 0.2 mg/m3, and that chronic exposure to polymeric MDI at a level of 6.0 mg/m3 was related to the occurrence of pulmonary tumors. It was also concluded that exposure to polymeric MDI at concentrations not leading to recurrent lung tissue damage will not produce pulmonary tumors.

Adenocarcinoma↗

Estimation of polymerization efficiency in the formation of polyacrylamide gel, using continuous optical scanning during polymerization.

The Ferguson plot and 'quantitative' gel electrophoresis (based on the Ferguson plot) depend on a knowledge of accurate gel concentrations. The easiest way to estimate accuracy of gel concentrations, in terms of the degree of completion of the polymerization reaction which gives rise to a gel, is by spectrophometry. Making use of the apparatus for continuous optical scanning of polyacrylamide gels, the extent and rate of polymerization of cross-linked polyacrylamide were estimated by measuring the absorbance at 275 nm of the reaction mixture subsequent to free radical initiation of polymerization. Under appropriate conditions of monomer concentration, initiator levels and temperature, absorbance decreased monotonically after a lag period of 10 min, and after 20--30 min of reaction the absorbance reached a plateau value which provided a measure of polymerization efficiency. Application of a standard curve of absorbance vs. monomer concentration allowed one to quantitate concentrations of residual monomer throughout the course of polymerization. Under a set of arbitrary polymerization conditions (e.g. 6--20% total gel concentration), the reaction went to 63--96% completion. The rate of polymerization was approximately proportional to the square of the monomer concentration (2nd-order reaction kinetics). Absorbance decrease subsequent to the initiation of the polymerization reaction appeared suitable as a measure of efficiency of polymerization since: (a) absorbance spectra of monomers at 0.5 %T and residual monomers in a 10 %T gel, at a time when polymerization seemed terminated, coincided; (b) values of residual monomer obtained were reasonable (10--30%); (c) bimolecular reaction kinetics were found, in agreement with expectation; and (d) absorbance of incomplete polymerization mixtures, deficient in either initiators or monomers, was constant with time.

Acrylamides↗

Mechanochemical solid-state polymerization (XI): effect of water-insoluble pharmaceutical aids on drug release from mechanically synthesized polymeric prodrugs.

We discuss here the effect of water-insoluble pharmaceutical aids on the nature of drug release from composite polymeric prodrugs synthesized by mechanochemical solid-state polymerization. Magnesium stearate (Mgst) and hydrogen castor oil (HCO) were used as water-insoluble pharmaceutical aids. Composite polymeric prodrugs were synthesized by the mechanochemical solid-state polymerization of a vinyl monomer of 5-fluorouracil (I) in the presence of Mgst or HCO. The molecular weight of the resulting polymeric prodrugs increased with increasing the content of Mgst or HCO. Prodrug hydrolysis was carried out in a heterogeneous system in phosphate buffer at pH 6.8 and 37 degrees C. The rate of drug release from the composite polymeric prodrug containing Mgst (Poly-Mgst) was faster than that from polymeric prodrug containing no pharmaceutical aids (Poly-Non), while hydrolysis of the composite polymeric prodrug containing HCO (Poly-HCO) was slower than Poly-Non. Scanning electron microscope (SEM) photos showed the surface of Poly-HCO was smoother than that of Poly-Non and Poly-Mgst. It was suggested that the slower drug release from Poly-HCO may be responsible for the smaller specific surface area than that of Poly-Non. It was also shown that the rate of drug release from the composite polymeric prodrugs decreases with increasing the content of Mgst or HCO. Hence, novel composite polymeric prodrugs with a variety of drug release rates can be prepared by mechanochemical solid-state polymerization in a totally dry process.

Pharmaceutic Aids↗

Yeast actin: polymerization kinetic studies of wild type and a poorly polymerizing mutant.

Wild-type actin and a mutant actin were isolated from yeast (Saccharomyces cerevisiae) and the polymerization properties were examined at pH 8.0 and 20 degrees C. The polymerization reaction was followed either by an increase in pyrene-labeled actin fluorescence or by a decrease in intrinsic fluorescence in the absence of pyrene-labeled actin. While similar to the properties of skeletal muscle actin, there are several important differences between the wild-type yeast and muscle actins. First, yeast actin polymerizes more rapidly than muscle actin under the same experimental conditions. The difference in rates may result from a difference in the steps involving formation of the nucleating species. Second, as measured with pyrene-labeled yeast actin, but not with intrinsic fluorescence, there is an overshoot in the fluorescence that has not been observed with skeletal muscle actin under the same conditions. Third, in order to simulate the polymerization process of wild-type yeast actin it is necessary to assume some fragmentation of the filaments. Finally, gelsolin inhibits polymerization of yeast actin but is known to accelerate the polymerization of muscle actin. A mutant actin (R177A/D179A) has also been isolated and studied. The mutations are at a region of contact between monomers across the long axis of the actin filament. This mutant polymerizes more slowly than wild type and filaments do not appear to fragment during polymerization. Elongation rates of the wild type and the mutant differ by only about 3-fold, and the slower polymerization of the mutant appears to result primarily from poorer nucleation.

Actins↗

Polymeric alkenoxy amino acid surfactants: IV. effects of hydrophobic chain length and degree of polymerization of molecular micelles on chiral separation of beta-blockers.

Four alkenoxy leucine-based surfactants with C8-C11 chains containing a terminal double bond, and one C11 chain surfactant with a terminal triple bond are synthesized and characterized in monomeric and polymeric forms. These polymeric pseudophases are then utilized to study the influence of chain length and DP for the enantioseparations of seven beta-blockers in MEKC. Variations in chain length and concentration of polymeric surfactants showed significant effects on the chiral resolution (Rs) and efficiency (N). A relatively large elution range combined with the highest polarity and aggregation number (A) but the lowest retention time, partial specific volume, and optical rotation generated with C8-polymeric surfactant results in simultaneous enantioseparation of all seven beta-blockers with higher N and R(s). In particular, highly hydrophobic beta-blockers are better resolved with shorter hydrocarbon chain even at higher surfactant concentration, which is unachievable with longer chain surfactant. On the other hand, polymer derived from C11-triple bond provided smaller A value compared to C11-double bond surfactant. However, chiral Rs of hydrophobic beta-blockers are still achievable with the C11-triple bond surfactant with enhanced N and shorter analysis time. In addition, effect of polymerization concentration is evaluated by polymerizing all five surfactants at five times their respective CMCs and 100 mM equivalent monomer concentrations. Polymerization of shorter chain (C8 and C9) double-bonded surfactants at five times their respective CMCs results in higher A values with better chiral Rs and N compared to the same two surfactants polymerized at 100 mM.

Adrenergic beta-Antagonists↗

Kinetics of the polymerization reaction of tobacco mosaic virus protein: transient-saturation type polymerization reaction.

The kinetics of the endothermic polymerization reaction of tobacco mosaic virus protein in the mild acid region was studied by means of temperature-jump (rising time of 6 sec)-turbidimetry, electron microscopy, and computer simulation. The time course profile of the turbidity increase changed from a normal one to an anomalous one as the size of the temperature-jump was made greater. The anomalous type polymerization profile, which we named the "transient-saturation" type, could be characterized by a rapid increase of turbidity and its transient saturation, and a slow increase to the final level. At a higher concentration of the protein, this transient-saturation effect was more marked, whereas the slow turbidity in the second phase occurred with a higher rate. This transient-saturation type polymerization profile was observed also in a pH-induced polymerization reaction. It was not observed in the case of the N-bromosuccinimide modified tobacco mosaic virus protein under a similar environmental change. By an electron microscopic study and computer simulation, it was revealed that in the first phase, a large number of short polymers were formed, and the concentration of the polymerizing units was rapidly reduced to the equilibrium value, and the polymerization reaction stopped transiently. In the second phase, polymer-polymer associations took place slowly and longer polymers were formed. The revlevance of the present study to the polymerization reaction of actin, myosin, and to a transient-overshoot type polymerization are discussed.

Bromosuccinimide↗

Polymerization of actin and actin-like systems: evaluation of the time course of polymerization in relation to the mechanism.

The time course of protein polymerization of the nucleation--elongation type is examined by using a general computer-simulation solution. For a simple nucleation--elongation scheme, it is shown that the half-time of polymerization is not necessarily a good measure of the nucleus size as has been previously suggested [Oosawa, F., & Kasai, M. (1962) J. Mol. Biol. 4, 10-21] since, depending on the mechanism, the apparent nucleus size, measured by a ratio of half-times at two actin concentrations, may be either larger or smaller than the real size. Steady-state equations developed by Wegner and Engel [Wegner, A., & Engel, J. (1975) Biophys. Chem. 3, 215-225] present a good description of the time course of polymerization although they are somewhat inflexible with regard to allowing for different mechanisms. Some of the assumptions implicit in the development of these equations are discussed in terms of the effect of changing individual rate constants or dissociation constants on the time course of polymerization. In addition, these steady-state equations have been expanded to include the consequences of a reversible first-order conformational change prior to polymerization. It is shown that a conformational change as a prerequisite to polymerization lengthens the lag time of polymerization and, depending on the conditions, may slow the rate of polymerization. The question of fragmentation and of reannealling is examined, and it is noted that simple relationships to describe these processes may not be possible.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗

Atom transfer radical polymerization from nanoparticles: a tool for the preparation of well-defined hybrid nanostructures and for understanding the chemistry of controlled/"living" radical polymerizations from surfaces.

Structurally well-defined polymer--nanoparticle hybrids were prepared by modifying the surface of silica nanoparticles with initiators for atom transfer radical polymerization and by using these initiator-modified nanoparticles as macroinitiators. Well-defined polymer chains were grown from the nanoparticle surfaces to yield individual particles composed of a silica core and a well-defined, densely grafted outer polystyrene or poly(methyl methacrylate) layer. In both cases, linear kinetic plots, linear plots of molecular weight (M(n)) versus conversion, increases in hydrodynamic diameter with increasing conversion, and narrow molecular weight distributions (M(w)/M(n)) for the grafted polymer samples were observed. Polymerizations of styrene from smaller (75-nm-diameter) silica nanoparticles exhibited good molecular weight control, while polymerizations of methyl methacrylate (MMA) from the same nanoparticles exhibited good molecular weight control only when a small amount of free initiator was added to the polymerization solution. The difference in polymerization behavior for styrene and MMA was ascribed to the facts that styrene undergoes thermal self-initiation while MMA does not and that termination processes involving freely diffusing chains are faster than those involving surface-bound chains. The polymerizations of both styrene and MMA from larger (300-nm-diameter) silica nanoparticles did not exhibit molecular weight control. This lack of control was ascribed to the very high initial monomer-to-initiator ratio in these polymerizations. Molecular weight control was induced by the addition of a small amount of free initiator to the polymerization but was not induced when 5--15 mol % of deactivator (Cu(II) complex) was added.

Journal Article↗

Polymerization of three hemoglobin A2 variants containing Val6 and inhibition of hemoglobin S polymerization by hemoglobin A2.

To understand determinants for hemoglobin (Hb) stability and Hb A2 inhibition of Hb S polymerization, three Valdelta6 Hb A2 variants (Hb A2 deltaE6V, Hb A2 deltaE6V,deltaQ87T, and Hb A2 deltaE6V, deltaA22E,deltaQ87T) were expressed in yeast, and stability to mechanical agitation and polymerization properties were assessed. Oxy forms of Hb A2 deltaE6V and Hb A2 deltaE6V,deltaQ87T were 2- and 1.6-fold, respectively, less stable than oxy-Hb S, while the stability of Hb A2 deltaE6V,deltaA22E,deltaQ87T was similar to that of Hb S, suggesting that Aladelta22 and Glndelta87 contribute to the surface hydrophobicity of Hb A2. Deoxy Hb A2 deltaE6V polymerized without a delay time, like deoxy Hb F gammaE6V, while deoxy Hb A2 deltaE6V,deltaQ87T and deoxy Hb A2 deltaE6V,deltaA22E,deltaQ87T polymerized after a delay time, like deoxy Hb S, suggesting that beta87 Thr is required for the formation of nuclei. Deoxy Hb F gammaE6V,gammaQ87T showed no delay time and required a 3.5-fold higher concentration than deoxy Hb S for polymerization, suggesting that Thr effects on Valdelta6 Hb A2 and Valgamma6 Hb F variants are different. Mixtures of deoxy Hb S/Hb A2 deltaE6V,deltaQ87T polymerized, like deoxy Hb S, while polymerization of Hb S/Hb A2 deltaE6V mixtures was inhibited, like Hb S/Hb F gammaE6V mixtures. These results suggest alpha2betaSdelta6 Val, 87 Thr hybrids and Hb A2 deltaE6V,deltaQ87T participate in Hb S nucleation, while only 50% of alpha2betaSdelta6 Val hybrids and none of the Hb A2 deltaE6V participate. These findings are in contrast to those of mixtures of Hb S with Hb F gammaE6V or Hb F gammaE6V,Q87T, which both inhibit Hb S polymerization. Our results also suggest participation in nucleation of some alpha2betaSdelta hybrids in A2S mixtures but not alpha2betaSgamma hybrids in FS mixtures.

Animals↗

Acute, subacute, and subchronic inhalation toxicity studies of respirable polymeric methylene diphenyl diisocyanate (polymeric MDI) aerosol in rats.

Short-term inhalation toxicity studies with respirable polymeric methylene diphenyl diisocyanate (polymeric MDI) aerosol were performed in rats. The 4-hr LC50 was found to be 490 mg polymeric MDI/m3 (95.5% < 4.3 microns). Exposure of (4-week-old) rats to 0, 2.2, 4.9, or 13.6 mg polymeric MDI/m3 (95% < 5 microns) for 2 weeks resulted in mortality, severe growth retardation, and elevated lung weights at 13.6 mg/m3; at 4.9 mg/m3 slight growth retardation and slightly elevated lung weights were observed. A 13-week study with 6-week-old rats exposed to 0.35, 1.4, or 7.2 mg polymeric MDI/m3 (95% < 5 microns) revealed transient growth retardation and a slightly increased number of pulmonary alveolar macrophages occasionally accompanied by increased numbers of mononuclear cells and fibroblasts in alveolar septa only at 7.2 mg/m3. In a second 2-week study with 4- or 6-week-old rats exposed to 14.1 mg polymeric MDI/m3 (95% < 5 microns), 4-week-old rats died earlier and in greater numbers than 6-week-old rats. In a second 13-week study with 6-week-old rats, using exposure concentrations of 0, 4.1, 8.4, and 12.3 mg polymeric MDI/m3 (95% < 5 microns) and including a 4-week recovery period, 12.3 mg/m3 induced mortality, growth retardation, severe respiratory distress, increased lung weights, degeneration and hyperplasia of the nasal epithelium, accumulations of macrophages in the lungs and mediastinal lymph nodes, and focal inflammatory changes in the lungs.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗

Structural difference between polymerized and non-polymerized fragment X, obtained by plasmin digest of fibrinogen.

Fragment X (LMrFX) was obtained as low molecular weight preparations from a late stage 2 plasmin digest of human fibrinogen. The thrombin-treated LMrFX preparations, which resulted in impaired polymerization, were further subfractionated into polymerized and non-polymerized components. The fractions were examined by SDS-PAGE and immunochemical methods. In polymerized fractions, more peptide bands were observed on SDS-PAGE in the reduced state than in non-polymerized fractions. Both fractions contained a similar number of internal cleavages in the A alpha, B beta and gamma chains, which are linked by disulfide bonds. Thus, the partial deficiencies in polymerization sites of the carboxy terminal region of the gamma chain and the amino terminal portions of the B beta chain, as well as internal cleavage, were considered to participate in the impairment of the thrombin-induced polymerization of LMrFX.

Amino Acid Sequence↗

Effectiveness of polymerization of a prosthetic composite using three polymerization systems.

STATEMENT OF PROBLEM: Although properties of laboratory-polymerized composite materials are influenced by the type of polymerizing unit, little information is available regarding the comparison between use of a high-intensity light source and application of secondary heat treatment. PURPOSE: This study examined properties of a prosthetic veneering composite polymerized with 3 polymerizing systems to evaluate the effects of varying polymerization modes on hardness, solubility, and depth of cure. MATERIAL AND METHODS: A composite material designed for a prosthetic veneer (Conquest Crown and Bridge) was polymerized using 3 methods: (1) exposure in the proprietary photopolymerizing unit with 2 halogen lamps (Cure-Lite Plus), followed by heating in an oven (Conquest Automatic Curing Unit); (2) exposure in a photopolymerizing unit with a xenon stroboscopic light source (Dentacolor XS); and (3) exposure in a photopolymerizing unit with 2 metal halide lamps (Hyper LII). Knoop hardness, water solubility, and depth of cure were determined for groups of 5 specimens, according to standardized testing methods. Data were compared using analysis of variance and the Duncan new multiple range test (P <.05). RESULT: The hardness number generated with the metal halide unit was statistically greater than those produced by the other 2 methods, and material component released into water was minimal when the material was exposed with the metal halide unit (P <.05). Among the 3 photopolymerizing units, the metal halide unit consistently exhibited the greatest depth of cure. CONCLUSION: Certain properties generated with the use of the high-intensity polymerizing unit exceeded those obtained from a proprietary system that requires a postheat treatment.

Analysis of Variance↗