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  • 1
    Electronic Resource
    Electronic Resource
    Interaction of turbulent plasma flow with a hypersonic shock wave (1997)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 81 (1997), S. 1073-1076 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: A transient increase is observed in both the spectral energy decay rate and the degree of chaotic complexity at the interface of a shock wave and a turbulent ionized gas. Even though the gas is apparently brought to rest by the shock wave, no evidence is found either of prompt relaminarization or of any systematic influence of end-wall material thermal conductivities on the turbulence parameters. © 1997 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.364441
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  • 2
    Electronic Resource
    Electronic Resource
    Desktop English (1996)
    Cambridge : Cambridge University Press
    Recall 8 (1996), S. 41-43 
    Details
    ISSN: 0958-3440
    Source: Cambridge Journals Digital Archives
    Topics: Linguistics and Literary Studies , Computer Science
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1017/S0958344000003426
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  • 3
    Electronic Resource
    Electronic Resource
    Encapsulation of proteins in bulk and thin film sol-gel matrices (1997)
    Springer
    Journal of sol gel science and technology 8 (1997), S. 629-634 
    Details
    ISSN: 1573-4846
    Keywords: protein encapsulation ; absorption spectroscopy ; thin films ; cytochrome c
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract This paper considers the nature of the interactions between the sol-gel derived inorganic matrix and a specific biomolecule, cytochrome c. Optical absorption and impedance spectroscopies are used to characterize the influence of synthesis conditions on the protein’s stability and conformation within the silica matrix. In some instances, encapsulation within the sol-gel matrix provides stabilization. For example, protein denaturation is reversible and aggregation is prevented. Moreover, the drying process does not negatively affect the protein; it is possible to regenerate the aged gel state by rehydration. The flexibility of the sol-gel process enables high quality cytochrome c-doped SiO2 thin films to be prepared. These films possess the characteristic reactivity and chemical function of cytochrome c in solution.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02436913
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  • 4
    Electronic Resource
    Electronic Resource
    Spectroscopic determination of cholinesterase activity and inhibition in sol-gel media (1997)
    Springer
    Journal of sol gel science and technology 8 (1997), S. 1067-1070 
    Details
    ISSN: 1573-4846
    Keywords: cholinesterase ; sol-gel ; pesticide ; THA ; enzyme activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Biological activity of cholinesterases can be determined by optically monitoring the enzymatic reaction with indophenyl acetate, (N-4′-acetoxyphenyl)-4-quinone imine. At pH 8.0 cholinesterases hydrolyze this yellow dye to yield a blue reaction product. Cholinesterase inhibitors reduce the rate of this hydrolysis. Thus, by monitoring absorbance of the hydrolysis product at its maximum (630 nm) as a function of time, reaction rates of both cholinesterase activity and cholinesterase inhibition may be quantified spectroscopically. Using this technique, we measured the enzymatic activity of butyrylcholinesterase (BuChE) molecules encapsulated in tetramethyl orthosilicate (TMOS) silicate gel-glass prepared by hydrolysis and condensation. This activity is reduced, in a concentration-dependent manner, by the reversible cholinesterase inhibitors 1,5-bis(4-allyldimethyl-ammoniumphenyl) pentan 3-one dibromide (BADAPP) and 9-amino-1,2,3,4-tetrahydroacridine (THA; tacrine, Cognex). The gel-glasses are rigid, and compact, transparent and porous enough to allow reagents to diffuse in and out.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02436985
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  • 5
    Electronic Resource
    Electronic Resource
    Cyclodextrins: Their Future in Drug Formulation and Delivery (1997)
    Springer
    Pharmaceutical research 14 (1997), S. 556-567 
    Details
    ISSN: 1573-904X
    Keywords: cyclodextrins ; drug formulation ; drug delivery ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Since their discovery, cyclodextrins and their ability to form inclusion complexes have fascinated chemists, formulators and recently, entrepreneurs. This mini-review has as its objective, a critical assessment of the current status of cyclodextrins in the formulation and delivery of pharmaceuticals and commentary on their potential future uses. The emphasis will be on answers to common questions often asked of pharmaceutical scientists working in this area. Why use cyclodextrins for drug solubilization and stabilization when alternative techniques are available? Why the greater interest in modified cyclodextrins and not the parent cyclodextrins? If a drug forms a strong cyclodextrin inclusion complex, how is the drug releasedin vivo? Does the injection of a cyclodextrin/drug complex alter the pharmacokinetics of the drug? Are there drug products on the market which contain cyclodextrins? What is the regulatory status of cyclodextrins? Although definitive answers to all these questions are not possible at this time, many of these questions are answerable, and educated and informed responses are possible for the rest.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1012136608249
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  • 6
    Electronic Resource
    Electronic Resource
    Esterase-Sensitive Cyclic Prodrugs of Peptides: Evaluation of an Acyloxyalkoxy Promoiety in a Model Hexapeptide (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 1615-1623 
    Details
    ISSN: 1573-904X
    Keywords: esterase-sensitive prodrug ; peptide delivery ; Caco-2 cells ; membrane permeability ; enzymatic stability ; chemical stability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To evaluate a cyclic acyloxyalkoxycarbamate prodrug of a model hexapeptide (H-Trp-Ala-Gly-Gly-Asp-Ala-OH) as a novel approach to enhance the membrane permeation of the peptide and stabilize it to metabolism. Methods. Conversion to the linear hexapeptide was studied at 37°C in aqueous buffered solutions and in various biological milieus having measurable esterase activities. Transport and metabolism characteristics were assessed using the Caco-2 cell culture model. Results. In buffered solutions the cyclic prodrug degraded chemically to the linear hexapeptide in stoichiometric amounts. Maximum stability was observed between pH 3–4. In 90% human plasma (t 1/2 = 100 ± 4 min) and in homogenates of the rat intestinal mucosa (t - = 136 ± 4 min) and rat liver (t - = 65 ± 3 min), the cyclic prodrug disappeared faster than in buffered solution, pH 7.4 (t - = 206 ± 11 min). Pretreatment of these media with paraoxon significantly decreased the degradation rate of the prodrug. When applied to the apical side of Caco-2 cell monolayers, the cyclic prodrug (t - = 282 ± 25 min) was significantly more stable than the hexapeptide (t - = 14 min) and at least 76-fold more able to permeate (P app = 1.30 ± 0.15 × 10−7 cm/ s) than the parent peptide (P app ≤ 0.17 × 10−8 cm/s). Conclusions. Preparation of a cyclic peptide using an acyloxyalkoxy promoiety reduced the lability of the peptide to peptidase metabolism and substantially increased its permeation through biological membranes. In various biological media the parent peptide was released from the prodrug by an apparent esterase-catalyzed reaction, sensitive to paraoxon inhibition.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016472119387
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  • 7
    Electronic Resource
    Electronic Resource
    The Importance of Structural Factors on the Rate and the Extent of N,O-acyl Migration in Cyclic and Linear Peptides (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 323-328 
    Details
    ISSN: 1573-904X
    Keywords: acyl migration ; peptides ; cyclosporin ; stability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The chemistry associated with the process of N,O-acyl migration was explored in both cyclic and linear peptides under aqueous acid conditions. The importance of backbone cyclization and N-methylation of the peptide bond on the kinetics of N,O-acyl migration in a series of linear and cyclic peptides related in structure to cyclosporin A (CsA) were examined. The similarity in the chemical reactivity of the cyclic peptide [MeLeu (3-OH)]1-CsA and the corresponding linear peptide [Val-MeLeu (3-OH)-Abu], suggested that for this series, cyclization of the peptide backbone may not play an important role in controlling the kinetics of N,O-acyl migration. In contrast, the disparity in the chemical reactivity of tripeptides [Val-MeLeu (3-OH)-Abu] and [Val-Leu (3-OH)-Abu], indicated that N-methylation of amide bond significantly impacted the kinetics. Various hypothesis are proposed to account for this observation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016231913858
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  • 8
    Electronic Resource
    Electronic Resource
    The Effect of Conformation on Membrane Permeability of an Acyloxyalkoxy-linked Cyclic Prodrug of a Model Hexapeptide (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 1657-1662 
    Details
    ISSN: 1573-904X
    Keywords: esterase-sensitive prodrug ; peptide delivery ; membrane permeability ; solution conformation ; nuclear magnetic resonance spectroscopy ; circular dichroism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To determine the different conformations of the acyloxyalkoxy-linked cyclic prodrug 1 of the model hexapeptide 2 in solution and to investigate the relationship between these solution conformations and the cellular permeability characteristics of this prodrug. Methods. Two-dimensional Homonuclear Hartmann-Hahn spectroscopy, Rotating-Frame Overhouser effect spectroscopy, circular dichroism and molecular dynamics simulations were used to find the solution conformers of cyclic prodrug 1. Results. Our spectroscopic findings suggest that cyclic prodrug 1 exhibits a major and a minor conformer in solution. The major conformer appears to have a well-defined secondary structure, which involves a β-turn and 4 → 1 intramolecular hydrogen bond, creating a compact structure with a reduced average hydrodynamic radius compared to the model hexapeptide 2. Conclusions. The increased ability of cyclic prodrug 1 to permeate membranes compared to the model hexapeptide 2 could be due to reduction in the average hydrodynamic radius of the molecule facilitating paracellular flux and/or the reduction in the hydrogen bonding potential facilitating transcellular flux.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016484522113
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  • 9
    Electronic Resource
    Electronic Resource
    Design and Evaluation of an Osmotic Pump Tablet (OPT) for Prednisolone, a Poorly Water Soluble Drug, Using (SBE)7m-β-CD (1998)
    Springer
    Pharmaceutical research 15 (1998), S. 1562-1568 
    Details
    ISSN: 1573-904X
    Keywords: osmotic pump ; controlled-porosity osmotic pump tablet ; (SBE)7m-β-CD ; cyclodextrins, HP-β-CD ; poorly water soluble drug ; prednisolone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The purpose of this study was to develop a controlled-porosity osmotic pump tablet (OPT) for poorly water soluble drugs using a sulfobutyl ether-β-cyclodextrin, (SBE)7m-β-CD or Captisol™, which acted as both a solubilizer and as an osmotic agent. Methods. Prednisolone (PDL) was chosen as a model drug for this study. The release of PDL from osmotic pump devices and tablets was studied. In vivo absorption of PDL from OPT was evaluated in male beagle dogs. Results. PDL release from the osmotic pump tablet with (SBE)7m-β-CD was complete. Another cyclodextrin, hydroxypropyl-β-cyclodextrin (HP-β-CD), and a sugar mixture of lactose and fructose resulted in incomplete release. Although PDL release from the OPT with (SBE)7m-β-CD and the sugar formulation displayed mainly zero-order release characteristics, the tablet utilizing HP-β-CD showed apparent first-order release characteristics. An in vivo absorption study in dogs correlated very well with the in vitro release profiles using the Japanese Pharmacopoeia dissolution method. Conclusions. The present results confirm that (SBE)7m-β-CD can serve as both the solubilizer and the osmotic agent for OPT of PDL, and modify the input rate of PDL without compromising oral bioavailability.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1011955117026
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  • 10
    Electronic Resource
    Electronic Resource
    The use of transgenic cell lines for evaluating toxic metabolites of carbamazepine (1996)
    Springer
    Cell biology and toxicology 12 (1996), S. 155-165 
    Details
    ISSN: 1573-6822
    Keywords: carbamazepine ; CYP3A4 ; cytotoxicity ; human lymphoblastoid cells ; MTT ; transgenic cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Human lymphoblastoid cell lines transgenic for human CYP450s were evaluated for the identification of toxic metabolites of the anticonvulsant drug carbamazepine (CBZ). Human CYP450 isoforms expressed by these cell lines included 1A1, 1A2, 2E1, 2A6 and 3A4. A dose-dependent inhibition of population growth from 50–200 μg/ml CBZ was detected by measuring cell number and respiration. The inhibition increased with the growth rate of the various lines, which correlated inversely with the presence of CYP450s, and may have been caused by CBZ itself. Cytotoxicity was observed only at the highest dose and in the line lacking transfected CYP450s. Microsomal preparations from hCYP3A4/OR cells converted CBZ into its principal oxidative metabolite, carbamazepine-10,11-epoxide (CBZ-E), at a rate of 630 pmol/min per mg protein, confirming a major role of CYP3A4 in this reaction. However, no CBZ-E (or any metabolite) was recovered from any whole-cell incubation even though hCYP3A4 cells readily converted testosterone to 6ß-hydroxytestosterone. This suggests that differences exist between whole-cell and microsomal preparations of lymphoblastoid cells in their ability to metabolize CBZ.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00148169
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