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  • Electronic Resource  (11)
  • pharmacokinetics  (5)
  • General Chemistry  (4)
  • IAPS-forskolin  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Mutation of two conserved arginine residues in the glucose transporter GLUT4 supresses transport activity, but not glucose-inhibitable binding of inhibitory ligands (1995)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 353 (1995), S. 36-41 
    Details
    ISSN: 1432-1912
    Keywords: Glucose transport ; IAPS-forskolin ; Insulin-regulated glucose transporter GLUT4
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two arginine residues (RR333/334) in the conserved GRR motif located in the endofacial loop between helix 8 and 9 of the glucose transporter GLUT4 were substituted for leucine and alanine, respectively. Reconstituted glucose transport activity of the construct (GLUT4-RR333/4LA) expressed in COS-7 or LM(TK-) cells was less than 10% of that of the wild-type GLUT4. In contrast, binding of the inhibitory ligand cytochalasin B and glucose-inhibitable photolabeling with IAPS-forskolin were not significantly affected. Exchange of a histidine residue (H337Q) previously believed to be involved in the binding of inhibitory ligands failed to affect any of the investigated parameters. These data suggest that positive charges in the GRR motif at the cytoplasmic surface of the transporter participate in the conformational changes of the carrier protein during the process of facilitated diffusion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00168913
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  • 2
    Electronic Resource
    Electronic Resource
    Mutation of two conserved arginine residues in the glucose transporter GLUT4 supresses transport activity, but not glucose-inhibitable binding of inhibitory ligands (1995)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 353 (1995), S. 36-41 
    Details
    ISSN: 1432-1912
    Keywords: Key words Glucose transport ; IAPS-forskolin ; Insulin-regulated glucose transporter GLUT4
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two arginine residues (RR333/334) in the conserved GRR motif located in the endofacial loop between helix 8 and 9 of the glucose transporter GLUT4 were substituted for leucine and alanine, respectively. Reconstituted glucose transport activity of the construct (GLUT4-RR333/4LA) expressed in COS-7 or LM(TK–) cells was less than 10% of that of the wild-type GLUT4. In contrast, binding of the inhibitory ligand cytochalasin B and glucose-inhibitable photolabeling with IAPS-forskolin were not significantly affected. Exchange of a histidine residue (H337Q) previously believed to be involved in the binding of inhibitory ligands failed to affect any of the investigated parameters. These data suggest that positive charges in the GRR motif at the cytoplasmic surface of the transporter participate in the conformational changes of the carrier protein during the process of facilitated diffusion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00168913
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    The effects of posture on the pharmacokinetics of intramuscular benzylpenicillin (1988)
    Springer
    European journal of clinical pharmacology 33 (1988), S. 629-635 
    Details
    ISSN: 1432-1041
    Keywords: benzylpenicillin ; posture ; intramuscular administration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Previous reports have produced conflicting results as to whether changes in posture affected the pharmacokinetics of the penicillins. We have studied the pharmacokinetics of intramuscularly administered benzylpenicillin in normal subjects during bedrest and ambulation and compared it with data obtained following intravenous administration of the same dose to the same subjects under the same conditions. The values of area under the curve, total clearance, mean residence time and renal clearance found during ambulation were 1175 (min·min·l−1), 488 (ml·min−1), 101 (min), and 264 (ml·min−1) (means). The corresponding values for bedrest were 1032 (min·mg·l−1), 544 (ml·min−1), 96.7 (min), and 315 (ml·min−1). There was a significant difference between the areas under the curve with change of posture but not between any of the other pharmacokinetic variables. The differences observed in this study are unlikely to be of clinical relevance. We suggest that the differences between the results of this study and those of previous studies may be related to the level of exercise undertaken by the subjects in the various studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542500
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  • 4
    Electronic Resource
    Electronic Resource
    Interaction of metoprolol with lorazepam and bromazepam (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 405-409 
    Details
    ISSN: 1432-1041
    Keywords: Metoprolol ; lorazepam ; bromazepam ; interaction ; psychomotor tests ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The interaction between metoprolol and bromazepam and lorazepam was studied in 12 healthy male volunteers aged 21–37 years. Metoprolol had no significant effect on the pharmacokinetics of bromazepam or lorazepam. However, bromazepam AUC was 35% higher in the presence of metoprolol. Bromazepam enhanced the effect of metoprolol on systolic blood pressure but not on diastolic blood pressure or pulse rate. Lorazepam had no effect on either blood pressure or pulse. Metoprolol did not enhance the effect of bromazepam on the psychomotor tests used in this study. Metoprolol caused a small increase in critical flicker fusion threshold with lorazepam but had no effect on the other tests. Lorazepam (2 mg) was more potent than bromazepam (6 mg) in the doses used in this study. The interaction of metoprolol with bromazepam and lorazepam is unlikely to be of clinical significance. No change in dose is necessary when using these drugs together.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265852
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  • 5
    Electronic Resource
    Electronic Resource
    The effect of posture on the pharmacokinetics of intravenous benzylpenicillin (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 731-734 
    Details
    ISSN: 1432-1041
    Keywords: benzylpenicillin ; intravenous administration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of intravenously administered benzylpenicillin in normal subjects during bedrest and during ambulation. The values of total body clearance, mean residence time, and renal clearance found during ambulation were 487.4±100.5 ml/min, 36.23±13.45 min, and 309.4±93.4 ml/min (means ± SD). The corresponding values for bedrest were 543.6±122.6 ml/min, 35.27±10.21 min, and 324.1±145.3 ml/min. There were no significant differences between any of these pharmacokinetic variables with the change in posture. These results differ from previously reported results for the effects of posture on the pharmacokinetics of penicillins administered by extravascular routes, and suggest that the absorption of benzylpenicillin may be dependent on posture.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00608225
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  • 6
    Electronic Resource
    Electronic Resource
    An Implantable Pump for Intrarenal Infusion of Immunosuppressants in a Canine Autotransplant Model (1988)
    Springer
    Pharmaceutical research 5 (1988), S. 781-785 
    Details
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; 6-mercaptopurine ; targeted drug delivery ; renal transplantation ; intraarterial infusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract We developed a canine renal allograft model utilizing implantable infusion pumps and biocompatible catheters to investigate the pharmacokinetics of local immunosuppressive drug administration. Seven mongrel dogs underwent bilateral nephrectomy and autotransplantation of one kidney to the iliac vessels. The proximal end of an infusion catheter directed into the iliac artery was tunneled to a subcutaneously placed programmable pump. A second, sampling catheter was placed with its tip in the iliac vein. Simultaneous regional (iliac vein) and systemic (jugular vein) venous concentrations of 6-mercaptopurine (6-MP), the immunosuppressive metabolite of azathioprine, were determined during a continuous 24-h intraarterial infusion (10 mg/kg/24 hr). The gradient between regional and systemic 6-MP concentrations was maximal initially when the pump was turned on, continuously decreased until steady state was reached, and disappeared immediately after the pump was turned off. The mean ratio of steady-state iliac vein to systemic 6-MP concentrations was 5.0 ± 1.4, demonstrating a pharmacokinetic advantage of continuous intraarterial 6-MP infusion to the autotransplanted kidney. The novel canine renal allograft model described herein overcomes the technical limitations of earlier models and represents a foundational step in the design of intrarenal infusion patterns of immunosuppressive agents which we expect to prolong survival of the allotransplanted kidney with minimal systemic drug exposure and side effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015940802451
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  • 7
    Electronic Resource
    Electronic Resource
    Liposomal Formulation Eliminates Acute Toxicity and Pump Incompatibility of Parenteral Cyclosporine (1989)
    Springer
    Pharmaceutical research 6 (1989), S. 601-607 
    Details
    ISSN: 1573-904X
    Keywords: liposome ; cyclosporine ; acute toxicity ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The currently available intravenous dosage form of cyclosporine (CSA), Sandimmune I.V., contains the vehicle, Cremophor EL, which has been implicated in producing anaphylactic reactions in man and animals. This formulation also leaches through silicone tubing, an important component of some automatic drug delivery devices, causing pump dysfunction. In an attempt to develop a less toxic and pump-compatible formulation of CSA, suitable for intrarenal infusion in a canine transplant model, we compared the acute toxicity, pharmacokinetics, and pump compatibility of emulsified (CSA/emulsion) and liposomal (CSA/liposomes) CSA preparations with those of Sandimmune I.V. and CSA dissolved in ethanol vehicle (CSA/alcohol) in healthy, unoperated dogs. Animals receiving Sandimmune I.V. demonstrated marked acute toxicity despite progressive 10-fold dose reduction and 〉50-fold prolongation of infusion duration. One of two animals receiving CSA/emulsion and both dogs receiving emulsion vehicle alone exhibited a moderately severe reaction, while five of seven dogs receiving CSA/alcohol demonstrated immediate, mild reactions. No discernible adverse reactions occurred in any animal receiving CSA/liposomes. Systemic disposition of CSA/alcohol and CSA/liposomes was similar. In contrast to the liposomal vehicle, the emulsion vehicle produced a marked, early weight gain and substantial decrease in tensile strength of the pump tubing, both of which would adversely affect pump function. These results provide the first description of liposomal CSA toxicology and pharmacokinetics in a large animal model and may lead to the successful development of a less toxic parenteral CSA formulation for systemic and local pump-based administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015905615404
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  • 8
    Electronic Resource
    Electronic Resource
    Verbindungen mit Si—Si-, Ge—Ge- und Sn—Sn-Doppelbindungen sowie gespannte Ringsysteme mit Si-, Ge- und Sn-GerüstenProfessor Emanuel Vogel gewidmet (1991)
    Weinheim : Wiley-Blackwell
    Zeitschrift für die chemische Industrie 103 (1991), S. 916-944 
    Details
    ISSN: 0044-8249
    Keywords: Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Als Höhepunkte auf dem Gebiet der Organoelementchemie der schwereren Elemente der vierten Hauptgruppe (Gruppe 14 des Periodensystems) in den 80er Jahren gelten die Darstellung und vollständige Charakterisierung dreier Verbindungsklassen, deren Existenz bis dahin aufgrund ihrer Reaktivität für nicht möglich gehalten wurde. Hierbei handelt es sich um 1) die dreigliedrigen Ringsysteme Cyclotrisilan, -trigerman und -tristannan, 2) Moleküle mit Element-Element-Doppelbindungen einschließlich Disilen, Digermen und Distannen sowie 3) gespannte Polycyclen mit einem Gerüst aus den schwereren Elementen der 4. Hauptgruppe, z. B. Bicyclo[1.1.0]tetrasilan, Hexagermaprisman und Octasilacuban. Die meisten dieser Verbindungen sind durch sperrige Substituenten stabilisiert. Die Verbindungen ermöglichten Untersuchungen über die Veränderungen physikalischer und chemischer Eigenschaften in Abhängigkeit vom Element und den Substituenten sowie über die thermische und photochemische Reaktivität dieser Systeme, wobei zweiwertige Carben-Analoga nachgewiesen wurden. Parallel zu den experimentellen Arbeiten wurden an nahezu allen im Beitrag diskutierten Stammverbindungen Rechnungen durchgeführt. Einige Polycyclen weisen den Weg zu Verbindungen mit einer Element-Element-Dreifachbindung.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ange.19911030805
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  • 9
    Electronic Resource
    Electronic Resource
    Wie die Natur Vitamin B12 synthetisiert - ein Überblick über die letzten vier Milliarden JahreNach einem Vortrag bei der 27. Euchem-Konferenz über Stereochemie, Bürgenstock (Schweiz). 26. April - 4. Mai 1992. Eine ausführlichere Übersicht zu diesem Forschungsgebiet findet sich in dem Beitrag “Genetically Engineered Synthesis of Complex Natural Products” (A. I. Scott. Tetrahedron 1992, 48, 2559). (1993)
    Weinheim : Wiley-Blackwell
    Zeitschrift für die chemische Industrie 105 (1993), S. 1281-1302 
    Details
    ISSN: 0044-8249
    Keywords: Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Diese Übersicht stellt neuere experimentelle Ergebnisse der Erforschung der unendlichen Geschichte der Vitamin-B12-Biosynthese vor, wobei hauptsächlich auf Arbeiten aus der Arbeitsgruppe des Autors zurückgegriffen wird. Darüber hinaus gibt sie einen persönlichen Ausblick auf die Zukunft der Naturstoff-Biosyntheseforschung. Von zentraler Bedeutung ist mittlerweile die leistungsfähige Kombination von molekularbiologischen und modernsten spektroskopischen Techniken. Jene dienen der Suche nach und der Expression von Genen, die für die Enzyme der Biosynthese codieren, diese machen die biochemischen Vorgänge im NMR-Röhrchen direkt beobachtbar. Als logische Weiterentwicklung dieser Ansätze wird die Durchführbarkeit der Eintopf-Multienzymsynthese von Naturstoffen vorgestellt. Dank der Entwicklung und Nutzung von Klonierungstechniken und der daraus resultierenden Verfügbarkeit von Enzymen für die C-C-Verknüpfung hat sich ein grundlegender Wandel im “Handwerkszeug“ des Bioorganikers vollzogen. Gleichzeitig seien aber auch die Organiker angesprochen, die sich diesen technischen Fortschritt zunutze machen wollen. Ihnen wird sich eine neue Welt natürlicher Katalysatoren erschließen, die Synthesen mit hohen Ausbeuten bei einem oftmals überraschenden, aber durchaus willkommenen Mangel an Substratspezifität versprechen. Und schließlich hoffen wir, unsere Begeisterung für diese modernen Methoden weiterzugeben, mit denen heutige wie auch künftige Generationen von Chemikern die Synthesewege der Natur zu komplexen Naturstoffen erforschen können.
    Additional Material: 24 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ange.19931050904
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  • 10
    Electronic Resource
    Electronic Resource
    Strained-Ring and Double-Bond Systems Consisting of the Group 14 Elements Si, Ge, and SnAbbreviations used in the text: Solvents and reagents: m-CPBA = metachloroperbenzoic acid; DCA = 9,10-dicyanoanthracene; DME = dimethoxyethane; TCNE = tetracyanoethylene. Substituent groups: 1-Ad = 1-adamantyl; Cy = cyclohexyl; Dep = 2,6-diethylphenyl; Dip = 2,6-diisopropylphenyl; Dis = bis(trimethylsilyl)methyl; Dit = 4-tert-butyl-2,6-diisopropylphenyl; Dmp = 2,6-dimethylphenyl; Dmt = 4-tert-butyl-2,6-dimethylphenyl; mes = mesityl(2,4,6-trimethylphenyl); Nep = neopentyl; Np = naphthalenide; Phen = 9-phenanthryl; Tip = 2,4,6-triisopropylphenyl; TMS = trimethylsilyl; p-Tol = p-tolyl; Tsi = tris(trimethylsilyl)methyl.Dedicated to Professor Dr. Emanuel Vogel. (1991)
    Weinheim : Wiley-Blackwell
    Angewandte Chemie International Edition in English 30 (1991), S. 902-930 
    Details
    ISSN: 0570-0833
    Keywords: Bond theory ; Tin ; Germanium ; Silicon ; Strained molecules ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The organometallic chemistry of the Group 14 elements E = Si, Ge, Sn in the 1980's is highlighted by the successful construction and characterization of three systems previously thought to be too reactive to exists: (1) three-membered ring compounds including cyclotrisilane, cyclotrigermane, and cyclotristannane, (2) molecules containing E—E double bonds including disilene, digermene, and distannene, and (3) strained polycycles containing a skeleton of Group 14 elements, such as bicyclo[1.1.0]tetrasilane, hexagemaprismane, and octasilacubane. The majority of these numerous compounds now available are fully substituted with bulky ligands to suppress the reactivity intrinsic to the systems. These compounds permit examinations of (1) the variation of physical and chemical properties of a system with these elements and also with the ligands and (2) how two systems are interrelated thermally and photochemically with the intermediacy of the divalent (carbene-like) species. Theoretical calculations on virtually all of the parent compounds discussed in this review are evaluated alongside the experimental results. Some polycycles may constitute a stepping-stone on the way to compounds with a triple bond.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/anie.199109021
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