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  • 1
    ISSN: 1432-1041
    Keywords: Diabetes ; Human insulin ; Lorazepam ; pharmacokinetics ; glucuronidation ; enterohepatic circulation ; animal insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics of lorazepam was examined in 10 male patients with insulin-dependent diabetes mellitus before and following treatment with neomycin and cholestyramine. Neomycin and cholestyramine were given in an attempt to block the enterohepatic circulation of lorazepam and so to permit an in vivo estimate of hepatic glucuronidation. The volume of distribution and clearance of free lorazepam in diabetic patients were not significantly different from the corresponding estimates in 14 normal controls. Neomycin and cholestyramine increased the clearance of lorazepam by 63% consistent with their effect in non-diabetic controls. However, patients on beef/pork insulin exhibited a greater than normal increase on this interupting regimen (125%), and had a significantly greater neomycin/cholestyramine cycling-interrupted clearance of lorazepam than either normal controls or patients on human insulin (15.4 vs. 6.96 and 7.87 ml·min−1·kg−1). The clearance was correlated positively and significantly with HbA1c and glycated proteins (fructosamine), but only in patients on human insulin. Thus, the pharmacokinetics of lorazepam was not altered in patients with insulin-dependent diabetes mellitus. However, it is possible that there are differences in the rate and extent of hepatic glucuronidation and enterohepatic circulation of lorazepam between patients treated with beef/pork and human insulins and between diabetics treated with beef/pork insulin and non-diabetic controls.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-904X
    Keywords: albumin ; granulocyte-colony stimulating factor ; polyethylene glycol ; protein conjugate ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Recombinant human granulocyte-colony stimulating factor (rhG-CSF) was covalently conjugated to both rat and human serum albumin (RSA and HSA respectively) to increases the circulating half life (t1/2) of rhG-CSF. Methods. Conjugates of RSA (MW 67,000) and HSA (MW 66,000) were prepared by linking the two proteins through a heterobifunctional maleimido-carboxyl polyethylene glycol (PEG) and were tested in the rat. The conjugates were injected intravenously (IV) at the equivalent dose of 50 µg/kg of rhG-CSF, and white blood cell (WBC) counts and plasma concentrations of drug were determined. A comparison of pharmacokinetic parameters was made between rhG-CSF, the conjugates RSA-PEG-rhG-CSF and HSA-PEG-rhG-CSF, and a non-covalent mixture of rhG-CSF and HSA. Results. The albumin-rhG-CSF conjugates are eliminated more slowly from the circulation. The clearance values are reduced from 0.839 ± 0.121 ml/mm/kg for rhG-CSF to 0.172 ± 0.013 ml/min/kgfor RSA-PEG-rhG-CSF and 0.141 ± 0.005 ml/mm/kg for HSA-PEG-rhG-CSF. WBC counts increased in both absolute number and duration as compared to rhG-CSF alone. The albumin rhG-CSF conjugates had enhanced serum stability relative to free rhG-CSF. The rate of degradation of the albumin conjugates incubated in rat serum at 37°C decreased five fold. Conclusions. The results from the study show that specific conjugation of rhG-CSF to albumin decreases plasma clearance in vivo, causes increased WBC response, and increases serum stability as compared to free rhG-CSF.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular neurobiology 19 (1999), S. 355-372 
    ISSN: 1573-6830
    Keywords: enantiomers ; racemic ; chiral ; stereoselective ; pharmacokinetics ; cytochrome P450 ; geometric isomers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 1. Many drugs used to treat psychiatric disorders contain a chiral center or a center of unsaturation and are marketed as a mixture of the resultant enantiomers or geometric isomers, respectively. These enantiomers or geometric isomers may differ markedly with regard to their pharmacodynamic and/or pharmacokinetic properties. 2. Examples of the effects of chiral centers or geometric centers on such properties are given for drugs from the following classes: antidepressants (tricyclics, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, viloxazine, bupropion, trazodone, mianserin, venlaflaxine); benzodiazepines, zoplicone, and antipsychotics. 3. As described in this review, there are several notable examples of psychiatric drugs currently available where the individual enantiomers or geometric isomers differ considerably with regard to factors such as effects on amine transport systems, interactions with receptors and metabolizing enzymes, and clearance rates from the body. Indeed, relatively recent developments in analytical and preparative resolution of racemic and geometric drug mixtures and increased interest in developing new drugs which interact with specific targets, which have been described in detail at the molecular level, have resulted in increased emphasis on stereochemistry in drug development.
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  • 4
    ISSN: 0935-9648
    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
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 0006-3525
    Keywords: short duplex DNA ; sequence-dependent hybridization reactions ; sequence-dependent melting stability ; oligomers ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Many important applications of DNA sequence-dependent hybridization reactions have recently emerged. This has sparked a renewed interest in analytical calculations of sequence-dependent melting stability of duplex DNA. In particular, for many applications it is often desirable to accurately predict the transition temperature, or tm, of short duplex DNA oligomers (∼ 20 base pairs or less) from their sequence and concentration. The thermodynamic analytical method underlying these predictive calculations is based on the nearest-neighbor model. At least 11 sets of nearest-neighbor sequence-dependent thermodynamic parameters for DNA have been published. These sets are compared. Use of the nearest-neighbor sets in predicting tm from the DNA sequence is demonstrated, and the ability of the nearest-neighbor parameters to provide accurate predictions of experimental tm's of short duplex DNA oligomers is assessed. © 1998 John Wiley & Sons, Inc. Biopoly 44: 217-239, 1997
    Additional Material: 2 Ill.
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  • 6
    ISSN: 0948-1907
    Keywords: Permalloy ; MOCVD ; Ferromagnetic thin films ; Magnetoresistance ; 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
    Notes: Thin films of elemental iron and nickel, plus a wide composition range of iron-nickel alloys, have been deposited by atmospheric pressure metal organic chemical vapor deposition at a growth temperature of 200°C, using iron pentacarbonyl and nickel tetracarbonyl as the source precursors. Detailed magnetoresistance measurements of the permalloy layers showed that the maximum value of magnetoresistance occurred at a composition of approximately 90 % Ni10 % Fe, and the maximum sensitivity occurred at approximately 80 % Ni20 % Fe, in accordance with literature values. In addition, both the application of an 80 mT magnetic field during deposition and the annealing of samples at temperatures higher than the growth temperature of 200°C improved the magnetic properties.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Applied Biomaterials 5 (1994), S. 109-115 
    ISSN: 1045-4861
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The purpose of this study was to examine the effects of particles, derived from metals commonly used in joint prostheses, on chondrocyte proliferation, metabolism, and morphology in vitro. Chondrocyte viability was influenced by the type and concentration of metal particle added. Cobalt was toxic to chondrocytes at all particle concentrations (0.83-0.000083%, v/v), whereas the chromium, titanium and titanium-aluminum particles only effected chondrocyte viability at high concentrations. The metabolic response of chondrocytes to particulate debris as assessed by caseinase, collagenase, and hexosaminidase activities were variable at low concentrations but were always reduced at high concentrations (0.83% v/v). Prostaglandin E2 levels in the medium showed a steady increase when particle load increased, except in the medium of chondrocytes exposed to titanium-aluminum. Scanning electron microscopy of chondrocytes exposed to titanium showed ruffled cell borders and frequent membrane blebbings. This was in contrast to chondrocytes exposed to cobalt, where the crenated appearance indicated cell death, and titanium-aluminum, where the cells appeared quiescent. These findings show that metal particles alter chondrocyte viability and metabolism and suggest that particulate debris may influence the integrity and stability of articular cartilage following hemiarthroplasty. © 1994 John Wiley & Sons, Inc.
    Additional Material: 5 Ill.
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  • 8
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Advanced Materials for Optics and Electronics 5 (1995), S. 163-175 
    ISSN: 1057-9257
    Keywords: ULSI ; high dielectric constant ; metal oxides ; deposition ; annealing ; characterisation ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology , Physics
    Notes: Flims of metal oxides, such as Ta2O5, Nb2O5, Al2O3, HfO2, ZrO2 and TiO2 have been fabricated by use of different precursor materials, deposition techniques and annealing techniques. Several analytical methods were applied to study the layers. New data of fundamental properties of these metal oxides are reported and related to practical features that are of importance in device design and manufacturing of advanced, highly integrated devices. This overview may facilitate the choice of an optimal combination of precursor material, deposition technique and corresponding annealing procedure for a specific application of these metal oxide films in microelectronics.
    Additional Material: 5 Ill.
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  • 9
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Advanced Materials for Optics and Electronics 1 (1992), S. 299-308 
    ISSN: 1057-9257
    Keywords: LPCVD ; Tantalum pentoxide ; High dielectric constant ; ULSI devices ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Electrical Engineering, Measurement and Control Technology , Physics
    Notes: A laminar flow low-pressure chemical vapour deposition (LPCVD) system (LAM IntegrityTM) has been used to deposit tantalum pentoxide (Ta2O5) from Ta(OEt)5 films in the presence of oxygen (O2) at 470 °C at a typical deposition rate of 4 nm min-1. Uniformities of 〈1.5% (SD 1σ) over a 150 mm silicon substrate were obtained. The layers were annealed under different conditions. It was discovered that the films did not change their stoichiometry as determined by Rutherford backscattering (RBS). The as-deposited films were amorphous but became crystalline (β-Ta2O5) at temperatures 〉 700 °C. The transmission electron microscopy (TEM) results on crystallisation behaviour were supported by X-ray diffraction data. The electrical properties of the Ta2O5 films have been characterised using MIS (metal/insulator/silicon) capacitor structures. Leakage values of 〈10-6 A cm-2 at 6 MV cm-1 equivalent applied electric field and breakdown strengths of 〉7 MV cm-1 at 1.6 μA were obtained for annealed layers. Compound dielectric constants (native silicon oxide thickness of about 2.5 nm plus Ta2O5 of various thicknesses) between 14 and 〉30 have been measured. The electrical properties reveal the potential use of Ta2O5 as a storage capacitor dielectric in 64 and 256 Mbit DRAM (dynamic random access memory) devices.
    Additional Material: 13 Ill.
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  • 10
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Applied Polymer Science 54 (1994), S. 2191-2193 
    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
    Additional Material: 2 Ill.
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