Leica CM3600 XP Fully Computerized Cryomacrotome for Whole-body Sectioning
This application brief presents a reliable, modified haematoxylin and eosin (HE) staining procedure for tape-mounted rat sections commonly used in pharmaceutical research projects.
Ramipril: Autoradiographic studies on transfer and binding sites of (3H) - Ramiprilat in the rat brain
Ramipril is a new angiotensin converting enzyme (ACE) inhibitor. The compound is an esterified prodrug which, upon absorption, is hydrolysed to the pharmacological active metabolite, the dicarboxylic acid Ramiprilat.
Inhibition of the converting enzyme (CE) has proven to be an effective therapeutic principle in the treatment of hypertension.
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Receptor Micro Autoradiography
Receptor Micro-Autoradiography was developed for the tissue localization of drugs. Since drugs are generally small molecular weight compounds acting through weak binding to specific receptors with limited capacity, the method is designed to provide high resolution and high sensitivity, and at the same time to preserve microscopic tissue structure with the compound retained at its original site in vivo. This method has been tested before its introduction with compounds known localized and applied for several decades to the study of drugs, demonstrating its high diagnostic and predictive value.
Receptor micro-autoradiography is based on the use of radiolabeled (predominantly 3H or 125I) compounds with high specific activity in conjunction with nuclear emulsion-coated slides and thin frozen sections cut in a cryostat.
Cellular and subcellular detail can be viewed. Associated radioactivity can be characterized and quantified. Time- and dose-related data of different compounds can be compared. A receptor-drug-homunculus can be created as a computer model to provide overviews and details about sites of deposition and specific binding, receptor-drug half lives, hierarchies of target affinities, and indications for therapeutic indices, side effects and toxicity.
Documentation of precise localization can give important clues for drug functions and can serve as a guide for histochemical, biochemical, functional and clinical follow-up for the development of new therapeutic applications. With its high diagnostic and predictive qualities, receptor micro-autoradiography is an indispensable tool for drug research and development.
Detailed information and instructions on the most effective experimental design, execution of technique, and evaluation of autoradiograms are contained in a recently published manual. The publication is called "Drug Localization in Tissues and Cells - Receptor Microscopic Autoradiography. A Basis for Tissue and Cellular Pharmacokinetics, Drug Targeting, Delivery, and Prediction", author: Walter E. Stumpf .
The book is available through the:
University of North Carolina
Bookstore in Chapel Hill (UNC Student Stores, Chapel Hill, NC 27599).
Please direct order inquiries to:
Phone: (919) 962-2420
Fax: (919) 962-9661