In contrast, a region distal to pact up to 150 by from the point of cleavage was essential. Scanning substitutions revealed that the pact side of the cleavage site is complex and may contain multiple cis-acting sequence elements in addition to pact. These results should facilitate the identification of transacting factors that bind to these elements and the elucidation of their functions. Such information will be critical for understanding the molecular basis of this complex process.”
“Introduction: There are several instances when it is BI 10773 concentration desirable to control brain concentration of pharmaceuticals, e.g., to modulate the concentration
of anesthetic agents to different desired levels fitting to different needs find more during the course of surgery. This has so far only been possible using indirect estimates of drug concentration such as assuming constant relation between tissue and blood including extrapolations from
animals.
Methods: A system for controlling target tissue concentration (UIPump) was used to regulate whole-brain concentrations of a central benzodiazepine receptor antagonist at therapeutic levels with input from brain kinetics as determined with PET. The system was tested by using pharmacological doses of flumazenil mixed with tracer amounts of [C-11]flumazenil. Flumazenil was used as a model compound for anesthesia. An infusion scheme to produce three different steady-state levels in sequence was designed based on kinetic curves obtained after bolus injection. The subjects (Sprague-Dawley rats, n = 6) were monitored in a microPET scanner during Oxymatrine the whole experiment to verify resulting brain kinetic curves.
Results: A steady-state brain concentration was rapidly achieved corresponding to a whole-brain concentration of 118 +/- 6 ng/ml. As the infusion
rate decreased to lower the exposure by a factor of 2, the brain concentration decreased to 56 +/- 4 ng/ml. A third increased steady-state level of anesthesia corresponding to a whole-brain concentration of 107 +/- 7 ng/ml was rapidly achieved.
Conclusion: The experimental setup with computerized pump infusion and PET supervision enables accurate setting of target tissue drug concentration. (C) 2008 Elsevier Inc. All rights reserved.”
“Human immunodeficiency virus type 1 (HIV-1) particle assembly mediated by the viral structural protein Gag occurs predominantly on the plasma membrane (PM). Although it is known that the matrix (MA) domain of Gag plays a major role in PM localization, molecular mechanisms that determine the location of assembly remain to be elucidated. We observed previously that overexpression of polyphosphoinositide 5-phosphatase IV (5ptaseIV) that depletes PM phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P-2] impairs virus particle production and redirects processed Gag to intracellular compartments.