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  • 1
    Electronic Resource
    Electronic Resource
    Predictability of the clinical potency of NSAIDs from the preclinical pharmacodynamics in rats (1996)
    Springer
    Inflammation research 45 (1996), S. 531-540 
    Details
    ISSN: 1420-908X
    Keywords: Antiinflammatory ; Analgesic ; Antipyretic ; pKa ; Octanol-water partition coefficient ; NSAIDs ; Animal models ; Carrageenin ED50
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective and Design: Relevance of the preclinical pharmacodynamic, toxicity and pharmacokinetic parameters predicting the clinical potency of nonsteroidal antiinflammatory drugs (NSAIDs) was evaluated. Material: Data for oral potencies of 24 NSAIDs in rats were collected from the literature and from New Drug Applications with respect to the following parameters: antiinflammatory, analgesic, antipyretic, acute ulcerogenic activities, acute toxicity, in vitro inhibition of prostaglandin synthesis, acid dissociation constant (pKa), octanolwater partition coefficient and elimination half-life. Treatment: Data for most of the in vivo parameters in rats were collected following single dose administration with the exception of adjuvant arthritis. Single and daily clinical doses were considered. All of these NSAIDs have been approved for marketing although not all have been sold in the USA. Methods: The preclinical data were compared to human dose (unit or daily doses) using single and multiple stepwise regression analyses. Results: Analyses suggest that NSAIDs are effective in all models of preclinical tests for fever, pain and inflammation, however, carrageenin-induced rat paw edema model is clearly the best predictor of human dose. Rank order of preclinical models for predicting human dose is carrageenin 〉yeast induced fever〉pressure induced pain=adjuvant arthritis in rats. The analysis suggested that the pain and adjuvant arthritis models in rats may also involve a prostaglandin independent mechanism. Of the two physicochemical factors tested, pKa contributed best to the carrageenin model towards predicting the clinical potency of NSAIDs. Mathematical relationships between human dose, carrageenin ED50 and pKa were established that may assist in the future clinical development of NSAIDs. Conclusions: Carrageenin-induced paw edema model in rats is the most robust predictor of the clinical potency of NSAIDs. Acid dissociation constant (pKa) appears to be a secondary contributor to the potency of NSAIDs. The relevance of the data analyses for developing cyclooxygenase-2 (COX-2) selective NSAIDs is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02342223
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  • 2
    Electronic Resource
    Electronic Resource
    The proto-oncogene Bcl-2 inhibits cellular toxicity of dopamine: possible implications for Parkinson's Disease (1997)
    Springer
    Apoptosis 2 (1997), S. 149-155 
    Details
    ISSN: 1573-675X
    Keywords: Apoptosis ; bcl-2 ; dopamine ; Parkinson's disease ; PC-12 ; proto-oncogene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract It is currently believed that excessive oxidant stress induced by metabolism of dopamine (DA), plays a major role in the pathogenesis of the selective nigrostriatal neuronal loss in Parkinson's disease. We recently showed that the neurotransmitter DA, in physiological concentrations, is capable of initiating apoptosis in cultured, post-mitotic sympathetic neurons. Bcl-2 is a proto-oncogene that blocks apoptosis. We now report that Bcl-2 is a powerful inhibitor of DA toxicity in PC-12 pheochromocytoma cells. We induced stable expression of Bcl-2 in PC-12 cells by transfection with recombinant pCMV5 expression vector, containing mouse bcl-2 (coding-sequence) cDNA. Cells expressing Bcl-2 manifested marked resistance to otherwise lethal (300 uM) in vitroconcentrations of DA. This protective effect was reflected in the trypan-blue test of cell survival, 3 H-thymidine incorporation and inhibition of the characteristic apoptotic morphologic alterations in scanning electron microscopic studies. Bcl-2 and associated control systems of apoptosis may have an important physiological role in restraining the apop-tosis-triggering potential of DA in nigrostriatal neurons. This novel field of research may yield insights into the pathogenesis of Parkinson's disease and lead to development of novel therapeutic approaches.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026408313758
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  • 3
    Electronic Resource
    Electronic Resource
    Dopamine-Induced Apoptosis Is Inhibited in PC12 Cells Expressing Bcl-2 (1997)
    Springer
    Cellular and molecular neurobiology 17 (1997), S. 289-304 
    Details
    ISSN: 1573-6830
    Keywords: Parkinson's disease ; dopamine ; dopamine-melanin ; apoptosis ; bcl-2 ; antioxidants
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 1. Degeneration of nigrostriatal dopaminergic neurons is the major pathogenic substrate of Parkinson's disease (PD). It is assumed that the lethal trigger is the accumulation of oxidative reactive species generated during metabolism of the natural neurotransmitter dopamine. 2. We have recently shown that dopamine is capable of inducing programmed cell death (PCD) or apoptosis in cultured postmitotic chick sympathetic neurons and rat PC12 pheochromocytoma cells. 3. The bcl-2 gene encodes a protein which blocks physiological PCD in many mammalian cells. In an attempt to elucidate further the mechanism of dopamine toxicity, we examined the potential protective effect of bcl-2 in PC12 cells which were transfected with the protooncogene. 4. In our experiments, Bcl-2 producing cells showed a marked resistance to dopamine toxicity. The percentage of nuclear condensation and DNA fragmentation visualized by the end-labeling method following dopamine treatment was significantly lower in bcl-2 expressing cells. Bcl-2 did not protect PC12 cells against toxicity induced by exposure to dopamine-melanin. Extracts of PC12 cells containing Bcl-2 inhibited dopamine autooxidation and formation of dopamine-melanin. Furthermore, the presence of Bcl-2 protected cells from thiol imbalance and prevented thiol loss following exposure to dopamine. 5. The protective effects of Bcl-2 against dopamine toxicity may be explained, in part, by its action as an antioxidant and by its interference in the production of toxic agents. The possible protection by Bcl-2 against neuronal degeneration caused by dopamine may play a role in the pathogenesis of PD andmay provide a new direction for the development of neuroprotective therapies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026390201168
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  • 4
    Electronic Resource
    Electronic Resource
    Optical characterization of solid-state coextruded PET (1985)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Applied Polymer Science 30 (1985), S. 251-262 
    Details
    ISSN: 0021-8995
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Amorphous poly(ethylene terephthalate) has been solid state coextruded to a series of draw ratios up to 4.4 at 50, 60, 70 and 90°C. These uniaxially drawn samples have been examined by optical microscopy and light scattering and for increases in crystallinity and birefringence as a function of draw ratio and draw temperature. The birefringence for PET may be among the highest yet reported - 0.21.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/app.1985.070300120
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  • 5
    Electronic Resource
    Electronic Resource
    Some mechanical and optical properties of CFN polymersSupported in part by a contract with the Office of Naval Research and in part by grants from the National Science Foundation and the Plax Corp. and by assistance from the Monsanto Chemical Co. (1960)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Applied Polymer Science 4 (1960), S. 349-353 
    Details
    ISSN: 0021-8995
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Mechanical and optical studies have been carried out on high temperature fluorinated triazine-derived elastomers. These behave as crosslinked rubbers, having low ultimate elongations and tensile strengths and showing a tendency toward development of a crystallike order.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/app.1960.070041212
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  • 6
    Electronic Resource
    Electronic Resource
    Scanning force microscopy and effective medium theory study of free-standing polyaniline thin films (1995)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part B: Polymer Physics 33 (1995), S. 2167-2173 
    Details
    ISSN: 0887-6266
    Keywords: scanning force microscopy ; electric conductivity ; polyaniline ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The technique of scanning force microscopy was used to study the nanometer-scale structure of NMP cast films of polyaniline. Noncontact mode images provide direct evidence that polyaniline prepared in this form is a granular conductor. The films were found to consist of micrograins whose size and density were determined by the pH of the acid solution used to protonate the films. At pH 7, the polyaniline films exhibited a mostly disordered structure, with small 2-10 nm particles visible. Protonation at pH 5 to pH 3 resulted in partial agglomeration of the primary particles into larger bundles, with sizes up to 75 nm. Treatment in solution pHs of 2 or less resulted in films consisting of close-packed bundles of dimension 20-30 nm. The conductivity of the films exhibited a sharp rise beginning with protonation at pH 2 or less. Effective medium theory (EMT), was used to model the macroscopic conductivity of these films based on the SPM measured microscopic film structure. Using the size and size distribution of polymer micrograins or bundles in a modified EMT, we are able to obtain predicted conductivities that are close to the measured values for these films. © 1995 John Wiley & Sons, Inc.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/polb.1995.090331508
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  • 7
    Electronic Resource
    Electronic Resource
    Morphology of a liquid-crystalline polyester film (1988)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part B: Polymer Physics 26 (1988), S. 515-526 
    Details
    ISSN: 0887-6266
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Morphological studies are reported for a thermotropic liquid crystalline polyester. Small angle light scattering studies were carried out as a function of temperature using Hv and Vv polarization with photographic as well as photometric techniques. No scattering was observed from a thin film cast from a dilute solution of the polymer in a highly volatile solvent. When the film was heated, scattering of light was observed above the glass transition temperature of the polyester. The scattering was found to be azimuthally dependent with Vv intensities being much higher than the corresponding Hv intensities. The size of the morphological features responsible for SALS patterns were calculated and were found not to change significantly with temperature ranging from glass transition temperature to the solid-nematic transition temperature of the polyester. The WAXS pattern of solution cast polymer was representative of an amorphous structure. Solution cast films heat treated under various conditions (all above the Tg of the polymer) contained crystalline as well as amorphous structures. The maximum apparent crystallinity for annealed samples was of the order of 30%.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/polb.1988.090260304
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  • 8
    Electronic Resource
    Electronic Resource
    Static small-angle x-ray scattering study of polymer deformation (1990)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part B: Polymer Physics 28 (1990), S. 1791-1812 
    Details
    ISSN: 0887-6266
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The small-angle x-ray scattering (SAXS) approach has been employed in an effort to understand the deformation mechanism of semicrystalline polymers in terms of submicroscopic structure of lamellae. Isotropic melt-pressed polyethylenes of low, medium, and high densities (LDPE, MDPE, and HDPE, respectively) having spherulitic texture were investigated by SAXS for various Static elongations between 10% and 40%. The SAXS isointensity contours of the deformed polymers are anisotropic (elliptical) with the long axis perpendicular to the stretching direction. Slice averages at various azimuthal angles between 0° and 90° reveal distinct SAXS peaks with respect to scattering angle. The peak position of SAXS profile characterizes the long period or lamellar spacing, while integrated intensity distribution is relevant to lamellar orientation. At low elongations, there is an increase in intensity at both azimuthal angles of 0° and 90°, suggesting that excess scattering arises during deformation, probably associated with lamellar untwisting process. Lamellar orientation distribution and second-order orientation are defined to account for the lamellar orientation process. Experimental results are compared with Kratky's floating rod model coupled with Stein's lamellar untwisting model. The lamellar orientation closely follows the affine deformation scheme, while the lamellar spacing deviates appreciably from it, particularly at large elongations.
    Additional Material: 20 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/polb.1990.090281011
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  • 9
    Electronic Resource
    Electronic Resource
    Ellipsometric study of the glass transition and thermal expansion coefficients of thin polymer films (1993)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part B: Polymer Physics 31 (1993), S. 319-326 
    Details
    ISSN: 0887-6266
    Keywords: thermal expansion ; thin films ; ellipsometer ; glass transition ; refractive index ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The glass transition (Tg) of thin polystyrene films (ca. 3000 A˚) cast on silicon wafers was determined by a new technique. An ellipsometer was used to determine the refractive index and thickness of the polystyrene films. Tg was determined by measuring the temperature dependence of the refractive index. The change in thickness with temperature was used to calculate the linear and bulk thermal expansion coefficients of the material. A significant shift in Tg, possibly due to strains induced in the cooled films, was observed between heating and cooling for polystyrene films. © 1993 John Wiley & Sons, Inc.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/polb.1993.090310310
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  • 10
    Electronic Resource
    Electronic Resource
    Nano-structured, semicrystalline polymer foams (1996)
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part B: Polymer Physics 34 (1996), S. 3063-3072 
    Details
    ISSN: 0887-6266
    Keywords: nano-structured foams ; semicrystalline polymers ; small-angle scattering ; platelet model ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Semicrystalline polymers gelled from thermally quenched semidilute solutions can, in some cases, be supercritically dried to produce nano-structured foams of exceedingly high specific surface area. This article investigates the nano-morphology of these semicrystalline foams. The common morphological feature that these systems display in small-angle scattering can be described by uncorrelated lamellar platelets. The morphological details, which can be obtained using microscopy and small-angle scattering, indicate that these low-density systems occupy a morphological niche between polymeric crystallites from dilute solutions, and spherulitic crystals derived from concentrated solutions and melts. Because these crystalline morphologies occur in concentration ranges between dilute and concentrated, they may offer simple insight into the mechanisms available for distortion of ideal, dilute-solution-derived crystallites as polymer concentration is increased. Several mechanisms for the observed distortions are proposed. © 1996 John Wiley & Sons, Inc.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
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