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  • 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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  • 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
    Superior laryngeal nerve block: An anatomical study (1995)
    New York, NY [u.a.] : Wiley-Blackwell
    Clinical Anatomy 8 (1995), S. 89-95 
    Details
    ISSN: 0897-3806
    Keywords: paraglottic space ; airway anaesthesia ; upper airway ; Life and Medical Sciences ; Miscellaneous Medical
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Superior laryngeal nerve anaesthesia is frequently used to facilitate endotracheal intubation in the awake patient. We have modified the transcutaneous approach to this nerve block to employ a short bevel needle. This improves tactile perception in performing the procedure thus simplifying identification of the correct depth of injection. This study was designed to determine the anatomical basis of superior laryngeal nerve anaesthesia and to estimate the success rate using our modified technique. At autopsy, 20 cadavers had nerve block performed substituting 0.02% methylene blue for local anaesthetic. Dissection was then performed to identify the anatomical structures stained by the simulated local anaesthetic. Additional dissections were performed in formalin-fixed cadavers. We found that the dye was injected into the paraglottic space bounded laterally by the thyrohyoid membrane and thyroid cartilage, medially by the laryngeal submucosa, caudad by the conus elasticus, cephalad by the hyoid bone, and anteriorly and posteriorly by the anterior and posterior thyrohyoid ligaments, respectively. The internal laryngeal nerve, the sensory branch of the superior laryngeal nerve, passed through this compartment and was heavily stained with simulated local anaesthetic. Resistance to the passage of the short bevel needle was provided by the lateral glossoepiglottic fold, not the thyrohyoid membrane as we had expected. Of 40 injections, 39 were deemed successful for a success rate of 97.5%. We conclude that this is a simple and highly successful technique for performing superior laryngeal nerve anaesthesia. © 1995 WiIey-Liss, Inc.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ca.980080202
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  • 9
    Electronic Resource
    Electronic Resource
    Environmental scanning electron microscope imaging examples related to particle analysis (1993)
    New York, NY [u.a.] : Wiley-Blackwell
    Microscopy Research and Technique 25 (1993), S. 393-397 
    Details
    ISSN: 1059-910X
    Keywords: Surface charging ; Environmental scanning electron microscopy ; Particles ; Filters ; Air samples ; Conductive coating ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Natural Sciences in General
    Notes: This work provides examples of some of the imaging capabilities of environmental scanning electron microscopy applied to easily charged samples relevant to particle analysis. Environmental SEM (also referred to as high pressure or low vacuum SEM) can address uncoated samples that are known to be difficult to image. Most of these specimens are difficult to image by conventional SEM even when coated with a conductive layer. Another area where environmental SEM is particularly applicable is for specimens not compatible with high vacuum, such as volatile specimens. Samples from which images were obtained that otherwise may not have been possible by conventional methods included fly ash particles on an oiled plastic membrane impactor substrate, a one micrometer diameter fiber mounted on the end of a wire, uranium oxide particles embedded in oil-bearing cellulose nitrate, teflon and polycarbonate filter materials with collected air particulate matter, polystryene latex spheres on cellulosic filter paper, polystyrene latex spheres “loosely” sitting on a glass slide, and subsurface tracks in an etched nuclear track-etch detector. Surface charging problems experienced in high vacuum SEMs are virtually eliminated in the low vacuum SEM, extending imaging capabilities to samples previously difficult to use or incompatible with conventional methods. © 1993 Wiley-Liss, Inc.
    Additional Material: 18 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jemt.1070250507
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  • 10
    Electronic Resource
    Electronic Resource
    A cortical granule-specific enzyme, B-1,3-glucanase, in sea urchin eggs (1987)
    New York, NY : Wiley-Blackwell
    Gamete Research 18 (1987), S. 339-348 
    Details
    ISSN: 0148-7280
    Keywords: B-1,3-glucanase ; cortical granules ; hyaline layer ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: The ultrastructural localization of B-1,3-glucanase in three species of sea urchin eggs was determined using a monospecific antibody in an electronmicroscopic immunogold procedure. In all three species, Lytechinus variegatus, Strongylocentrotus purpuratus, and Arbacia punctulata, B-1,3-glucanase was localized specifically to the cortical granules. No other organelle within the egg contained significant label. During the fertilization reaction, B-1,3-glucanase was released from cortical granules into the perivitelline space and became associated with the hyaline layer. No significant label was found in association with the fertilization envelope.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/mrd.1120180408
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