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  • 1995-1999  (4)
  • 1880-1889
  • electrolytic injury  (2)
  • molecular dynamics  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Molecular and cellular biochemistry 192 (1999), S. 143-156 
    ISSN: 1573-4919
    Keywords: molecular dynamics ; LBP ; FABP ; structure-function ; protein-lipid interactions ; rational drug design
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Molecular dynamics computer simulations can provide a third leg which balances the contributions of both structural biology and binding studies performed on the lipid binding protein family. In this context, these calculations help to establish a dialogue between all three communities, by relating experimental observables with details of structure. Working towards this connection is important, since experience has shown the difficulty of inferring thermodynamic properties from a single static conformation. The challenge is exemplified by ongoing attempts to interpret the impact of mutagenesis on structure and function (i.e. binding). A detailed atomic-level understanding of this system could be achieved with the support of all three legs, paving the way towards rational design of proteins with novel specificities. This paper provides an outline of the connections possible between experiment and theory concerning lipid binding proteins.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-742X
    Keywords: venous thrombosis ; antithrombotic ; direct thrombin inhibitor ; electrolytic injury
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Deep venous thrombosis (DVT) is a common cardiovascular disease, resulting in significant mortality each year in the United States. Direct thrombin inhibitors represent a new class of drugs that could potentially be better than conventional antithrombotic therapy based on indirect inhibition of coagulation factors with heparin and warfarin. BCH 2763 is a potent, selective bifunctional thrombin inhibitor that blocks both the active catalytic site and the anion binding exosite. The objective of this study is to test the antithrombotic efficacy of BCH 2763 in a canine model of DVT induced through electrolytic injury to the femoral vein. BCH 2763 was administered at three dose levels: 0.125 mg/kg bolus followed by 10 µg/kg/min IV infusion (low-dose; n = 5), 0.25 mg/kg bolus followed by 20 µg/kg/min infusion (mid-dose; n = 5), and 0.75 mg/kg bolus followed by 60 µg/kg/min (high-dose; n = 5). The control group (n = 5) received a 5-ml intravenous bolus of saline followed by a 1 mL/kg/h infusion. The parameters evaluated were changes in activated partial thromboplastin time (aPTT), thrombin time (TT), prothrombin time (PT), time to formation of an occlusive thrombus in the femoral vein, and the amount of venous blood flow delivered over the course of the experiment. There were significant dose-dependent increases in aPTT, TT, and PT in the BCH 2763-treated animals compared with the control group. The time to formation of an occlusive thrombus in the control group averaged 69.6 ± 9 minutes. Treatment with BCH 2763 prolonged the time to occlusion to 126.4 ± 13 minutes in the low-dose group, 155.4 ± 17 minutes in the mid-dose group, and 229 ± 7 minutes in the high-dose group (80% remained patent for the duration of the study), which were all significantly greater than the controls. Femoral venous blood flow was significantly greater in the mid-dose (51 ± 8%) and the high-dose (70 ± 6%) groups compared with the control vessels (22 ± 3%). In conclusion, the results of this study indicate that BCH 2763 is an effective intravenous antithrombotic agent in the canine electrolytic injury model of venous thrombosis.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-742X
    Keywords: enoxaparin ; inogatran ; electrolytic injury ; venous thrombosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The objective of this study was to compare the effectiveness of the low molecular weight heparin, enoxaparin (Lovenox®), and inogatran (a direct thrombin inhibitor) in a canine electrolytic injury model of venous thrombosis. Effectiveness was defined as the ability of either drug to prolong the following parameters: activated partial thromboplastin time (aPTT), thrombin time (TT), prothrombin time (PT), and time to formation of an occlusive thrombus in the vein. There were 5 dogs and 10 vessels for each group (the right and left femoral veins were used in each dog to measure time to occlusion). Dogs were randomly assigned to one of six groups: (1) saline controls; (2) low-dose inogatran (0.075 mg/kg IV bolus followed by a 5 μg/kg/min infusion); (3) mid-dose inogatran (0.25 mg/kg IV bolus followed by a 20 μg/kg/min infusion); (4) high-dose inogatran (0.75 mg/kg IV bolus followed by a 50 μg/kg/min infusion); (5) low-dose enoxaparin (100 units/kg IV bolus followed by a 50 U/kg/h infusion); and (6) high-dose enoxaparin (200 U/kg IV bolus followed by a 100 U/kg/h infusion). Administration of inogatran resulted in dose-dependent increases in aPTT, TT, and PT, and administration of enoxaparin resulted in dose-dependent increases in aPTT and TT. There were no changes in hemodynamics. The time to occlusion in the control group averaged 81.7 ± 9.9 minutes compared with 141.8 ± 12.7, 185.8 ± 17.6, and 226.9 ± 8.8 minutes with the low, mid, and high doses of inogatran, and 131 ± 20.3, and 183.0 ± 19.0 minutes with the low and high doses of enoxaparin. Bleeding times were elevated by inogatran and enoxaparin, but no appreciable differences were detected between the two compounds. In summary, the direct thrombin inhibitor inogatran, administered intravenously, was as effective as the low molecular weight heparin enoxaparin in a canine model of venous thrombosis induced by electrolytic injury, supporting the conclusion that direct antithrombins may prove useful for prevention and treatment of deep venous thrombosis.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    International Journal of Quantum Chemistry 69 (1998), S. 105-116 
    ISSN: 0020-7608
    Keywords: bacteriorhodopsin ; protein: lipid interactions ; α-helices ; molecular dynamics ; membrane protein tertiary structure prediction ; Chemistry ; Theoretical, Physical and Computational Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The two-stage model of membrane protein folding predicts that isolated transmembrane α-helices form stably in the bilayer before coming together to form the fully functional protein. Insight into the molecular implications of this model are possible with detailed molecular dynamics calculations. Thirty molecular dynamics simulations of both individual and pairs of α-helices from bacteriorhodopsin were calculated with the CHARMm program. This data base will continue to grow and expand. Already, differences between identical helices in different media and different helices in the same media have been found. The current results are summarized in this contribution.   © 1998 John Wiley & Sons, Inc. Int J Quant Chem 69: 105-116, 1998
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
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