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  • 21
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Rapid Communications in Mass Spectrometry 9 (1995), S. 1418-1430 
    ISSN: 0951-4198
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Physics
    Notes: The metabolism of ranolazine (RS-43285) or (+)N-(2,6-dimethylphenyl)-4-[2-hydroxy-3-(2-methoxyphenoxy)-propyl]-1-piperazine acetamide dihydrochloride was investigated in man using plasma samples obtained from four different clinical studies. The metabolite profiles following single and multiple doses of 342 mg instant release (IR) ranolazine, following multiple doses of 1000 mg sustained release (SR) ranolazine and following dosing with both ranolazine (IR) and a potentially co-administered drug, diltiazem, were compared. Metabolism of ranolazine in man was shown by LC/MS analysis to be extensive with up to seven primary routes of metabolism identified. N-dealkylation by hydrolysis at the piperazine ring produced three metabolites whilst O-demethylation and O-dearylation at the methoxyphenoxy moiety produced a further two compounds. Additionally, hydrolysis of the amide group formed one other species. Oxygenation at various points in the molecule produced a further four metabolites. Direct conjugation of ranolazine with glucuronic acid and with an uncharacterized adduct were also identified as a route of elimination. Ten other biotransformation products were formed as a result of multiple metabolic steps. Conjugation was also associated with the desmethyl metabolite (glucuronide and unidentified conjugates) of hydroxylated ranolazine. In a previous publication (Journal of Chromatography, 1995, accepted for publication) semi-quantitative analyses of pooled plasma from the study where ranolazine was dosed at 1000 mg twice daily showed that of the twelve metabolites studied only four accounted for AUC's in excess of 10% of the ranolazine AUC.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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  • 22
    ISSN: 0952-3499
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The mobility of purified μ opioid binding protein in SDS-polyacrylamide gek electrophoresis is sensitive to the presence of reducing agents. In the presence of increasing concentrations of DTT the apparent molecular weight increases in a stepwise fashion from 53 kDa to 65 kDa. This reduction in mobility is attributed to the successive breakage of disulfide bridges, resulting in an increasingly asymmetric molecule. Treatment of cell membranes from various brain areas with reducing agents, such as DTT, produced a concentration-dependent inhibition of opioid binding. Sensitivity to DTT inhibition varied between receptor types, μ 〉 δ ≫ κ. For μ receptors, agonist binding was considerably more sensitive to DTT than antagonist binding. Inhibition by DTT is readily reversible and is unaffected by Na+ and/or Mg2+ ions. Reversibility may be partially prevented by the inclusion of a low concentration of a reducing reagent such as glutathione which does not inhibit binding but blocks reformation of disulfide bonds. Scatchard analysis of saturation data shows that DTT causes a pronounced decrease in binding affinity with little effect on receptor number. It is suggested that disulfide bonds are essential for ligand binding and that cleavage of one or more of these bonds may play a role in opioid receptor activation by agonists.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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  • 23
    Electronic Resource
    Electronic Resource
    Stamford, Conn. [u.a.] : Wiley-Blackwell
    Polymer Engineering and Science 17 (1977), S. 325-334 
    ISSN: 0032-3888
    Keywords: Chemistry ; Chemical Engineering
    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: Mortar specimens were impregnated with methyl methacrylate, n-butyl acrylate, styrene, and crosslinking agents in various combinations. After polymerization of the monomers in situ, studies of mechanical properties such as Young's modulus and compressive strength were made. In one experiment, various ccpolymers of methyl methacrylate and n-butyl acrylate were prepared and tested as a function of temperature. Excellent reinforcement was obtained with any combination of monomers as long as the resulting polymer was at a temperature below its glass transition temperature. This suggests that the modulus of the reinforcing polymer is crucial, glassy behavior being required. The addition of crosslinking agents such as TMPTMA increased the high temperature strength, however.
    Additional Material: 12 Ill.
    Type of Medium: Electronic Resource
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  • 24
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 21 (1987), S. 247-261 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Bone-particle-impregnated bone cement specimens (up to 30% by weight) were characterized by various test methods. The experimental bone cement showed decreased crack propagation rates and increased Young's modulus, while the ultimate tensile strength and impact strength were decreased. The viscosity could be adjusted by adding initiators lost when substituting the PMMA powder with bone particles. The present study warranted fur-ther in vivo experiments on the possibility of tissue ingrowth for which the new bone cement was developed.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
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  • 25
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 25 (1991), S. 141-156 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: To evaluate an experimental inorganicbone-particle-impregnated bone cement, canine hip prostheses were implanted in dogs using a regular bone cement on one side and the experimental bone cement on the other. In a preliminary feasibility study, bone ingrowth into the resorbed bone-particle spaces was established 3 months after implantation in three dogs. In a more detailed study, twenty-eight (28) dogs were divided in four groups to delineate the effects of time on the phenomena of bony ingrowth. One month after implantation, active bone ingrowth into the bone cement was obvious. By 3 months postimplantation, the ingrowth appeared to have traversed the thickness of the bone-particle-impregnated cement. By the fifth month, most of the interconnected inorganic bone particles were replaced by new bone. At the end of a year, the ingrown bone was mature and negligible new bone activity was present. Biomechanical pushout tests closely corroborated the histologic observations. The maximum shear strength of the cement/bone interface of the experimental side reached 3.6 times that of the control side at 5 months postimplantation. No further improvements were seen at 12 months postimplantation. A viable bone/cement interface may result in a better orthopedic implant fixation system by combining the advantages of both cement for immediate rigidity and biological ingrowth for longterm stability.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
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  • 26
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 27 (1993), S. 277-280 
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 27
    ISSN: 0021-9304
    Keywords: implant ; titanium ; osteoblasts ; surface roughness ; 1α,25- (OH)2D3 ; differentiation ; local factor ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Surface roughness has been shown to affect differentiation and local factor production of MG63 osteoblast-like cells. This study examined whether surface roughness alters cellular response to circulating hormones such as 1α,25-(OH)2D3. Unalloyed titanium (Ti) disks were pretreated with HF/HNO3 (PT) and then were machined and acid-etched (MA). Ti disks also were sandblasted (SB), sandblasted and acid etched (CA), or plasma sprayed with Ti particles (PS). The surfaces, from smoothest to roughest, were: PT, MA, CA, SB, and PS. MG63 cells were cultured to confluence on standard tissue culture polystyrene (plastic) or the Ti surfaces and then treated for 24 h with either 10-8M or 10-7M 1α,25-(OH)2D3 or vehicle (control). Cellular response was measured by assaying cell number, cell layer alkaline phosphatase specific-activity, and the production of osteocalcin, latent (L) TGFβ, and PGE2. Alkaline phosphatase activity was affected by surface roughness; as the surface became rougher, the cells showed a significant increase in alkaline phosphatase activity. Addition of 1α,25-(OH)2D3 to the cultures caused a dose-dependent stimulation of alkaline phosphatase activity that was synergistic with the effect caused by surface roughness alone. 1α,25-(OH)2D3 also caused a synergistic increase in osteocalcin production as well as local factor (LTGFβ and PGE2) production on the rougher CA, SB, and PS surfaces, but it had no effect on the production on smooth surfaces. The inhibitory effect of surface roughness on cell number was not affected by 1α,25-(OH)2D3 except on the SB surface. 1α,25-(OH)2D3 decreased cell number, increased alkaline phosphatase activity and osteocalcin production, and had no effect on LTGFβ or PGE2 production by MG63 cells grown on tissue culture polystyrene. These data suggest that bone cell response to systemic hormones is modified by surface roughness and that surface roughness increases the responsiveness of MG63 cells to 1α,25-(OH)2D3. They also suggest that the endocrine system is actively involved in normal bone healing around implants. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 77-85, 1998.
    Additional Material: 6 Ill.
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  • 28
    ISSN: 0021-9304
    Keywords: implant ; titanium ; osteoblasts ; prostaglandin ; indomethacin ; surface roughness ; 1α,25-(OH)2D3 ; differentiation ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Surface roughness affects proliferation, differentiation (alkaline phosphatase and osteocalcin), local factor production [transforming growth factor (TGFβ) and prostaglandin E2 (PGE2)], and response to 1,25-(OH)2D3 (1,25) of MG63 osteoblast-like cells. In this study, we examined whether the effect of surface roughness on MG63 cells is mediated by prostaglandins produced by the cells. Unalloyed titanium (Ti) disks were pretreated with HF/HNO3 (PT) and then machined and acid-etched (MA). Disks were also coarse grit-sandblasted (SB), coarse grit-sandblasted and acid-etched (CA), or plasma-sprayed with Ti particles (PS). The surfaces, from smoothest to roughest, were PT, MA, CA, SB, and PS. MG63 cells were cultured to confluence on the Ti disks in the presence or absence of 10-7M indomethacin (Indo), a specific inhibitor of cyclooxygenase activity, resulting in decreased prostaglandin production. When the cells reached confluence, cell number, cell layer alkaline phosphatase specific activity (ALPase), and osteocalcin (OC) and latent TGFβ (LTGFβ) production were determined. In addition, confluent cultures which had been grown in the absence of Indo were exposed to 10-7M 1,25, 10-7M Indo, or a combination of the two for 24 h. On the rougher surfaces, cell number was decreased and ALPase, OC, and LTGFβ were increased. When indomethacin was present throughout the culture period, the effect of surface roughness on cell number, OC, and LTGFβ was abolished. ALPase was reduced, but surface roughness-dependent effects were still observed. Addition of indomethacin to confluent cultures for 24 h had no effect on any of the parameters examined, with one exception: Cells cultured on MA surfaces exhibited a more differentiated phenotype. 1,25 increased all parameters examined on SB, CA, and PS surfaces. When indomethacin was added with 1,25, the 1,25-dependent effects on cell number and OC and LTGFβ production were abolished; however, ALPase was unaffected. This indicates that bone cell response to systemic hormones may be modified by implant surface roughness. This effect may be mediated, at least in part, by prostaglandins produced by the same cells. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 489-496, 1998.
    Additional Material: 8 Ill.
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  • 29
    Electronic Resource
    Electronic Resource
    Brookfield, Conn. : Wiley-Blackwell
    Polymer Composites 15 (1994), S. 479-487 
    ISSN: 0272-8397
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Graphite fiber reinforced epoxy composites normally exhibit low impact strength, poor delamination resistance, and low damage tolerance. Because delamination is a matrix-dominated failure mode, tougher matrix resins may be utilized to reduce or eliminate the adverse effects of delamination on the structural integrity of fiber composites. The effects of modifying epoxy network morphology by introducing polyurethane in the form of an interpentrating network were studied. The compatibility, toughness, and tensile properties of the matrix as well as the properties of the resultant laminates were evaluated. One of the conclusions arising was that the interpenetrating network morphology results in superior resin and composites toughness with increasing polyurethane content. However, the benefits of increased resin toughness did not necessarily translate into proportionally increased composite owing to the geomertical limitations placed on the plastic deformation zones in laminates.
    Additional Material: 15 Ill.
    Type of Medium: Electronic Resource
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  • 30
    Electronic Resource
    Electronic Resource
    Brookfield, Conn. : Wiley-Blackwell
    Polymer Composites 15 (1994), S. 488-495 
    ISSN: 0272-8397
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Hybrid resins of unsaturated polyester/urethane were synthesized and characterized. Both the toughness and stiffness of the polyester were improved significantly by incorporating 20 wt% urethane. Unsaturated polyester, styrene, and ethane showed good compatibility during blending and probably formed a simultaneous interpenetrating network (IPN) during polymerization. The resultant IPN morphology possessed a unique glass transition temperature. This IPN morphology not only imparted great fracture resistance to the otherwise brittle polyester, but also changed the fracture mode of new resin composites. The molecular weight of unsaturated polyesters did not have significant effect on the mechanical properties, but did exert an apparent influence on the fracture mode. During the cure process the side reaction, an amine reaction, could be suppressed addition of suitable promoter and catalyst.
    Additional Material: 12 Ill.
    Type of Medium: Electronic Resource
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