Methods and findings in experimental and clinical pharmacology
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Methods Find Exp Clin Pharmacol · Apr 2006
ReviewTherapeutic potential of cannabinoid receptor ligands: current status.
There are at least two types of cannabinoid receptors, CB1 also named CNR1 and CB2 also named CNR2, both coupled to G proteins. CB1 receptors exist primarily on central and peripheral neurons. CB2 receptors are present mainly on immune cells. ⋯ Following their release, endocannabinoids are removed from the extracellular space and then degraded by intracellular enzymic hydrolysis. CB1/CB2 agonists are already used clinically as antiemetic or to stimulate appetite. Potential therapeutic uses of cannabinoid receptor agonists include the management of multiple sclerosis, spinal cord injury, pain, inflammatory disorders, glaucoma, bronchial asthma, vasodilatation that accompanies advanced cirrhosis, and cancer.
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Methods Find Exp Clin Pharmacol · Sep 2005
ReviewSpecification of laboratory animal use in scientific articles: current low detail in the journals' instructions for authors and some proposals.
The scientific article communicates results of research to other investigators; therefore, it must contain a complete description of the experiment to help other researchers when designing their future investigations. However, poorly detailed data on laboratory animal use is given in published articles. Despite the well-known and important contribution of the International Committee of Medical Journal Editors (ICMJE) to standardize scientific writing and submission of manuscripts to biomedical journals, no specific instructions on the reporting of animal use are given in the ICMJE Uniform Requirements and, therefore, most journals do not detail this to the authors. ⋯ The present article relates some proposals for helping authors when reporting animal use in scientific articles. These proposals are not only based on previous guidelines for animal specifications, but also on Instructions for Authors from journals specialized in Laboratory Animal Science. These proposals are classified into major and minor issues, and they are located in the corresponding parts of the article, as defined by the Introduction, Methods, Results, and Discussion (IMRAD) method.
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Cytidine 5'-diphosphocholine, CDP-choline or citicoline, is an essential intermediate in the biosynthetic pathway of the structural phospholipids of cell membranes, especially in that of phosphatidylcholine. Upon oral or parenteral administration, CDP-choline releases its two principle components, cytidine and choline. When administered orally, it is absorbed almost completely, and its bioavailability is approximately the same as when administered intravenously. ⋯ Beneficial neuroendocrine, neuroimmunomodulatory and neurophysiological effects have been described. CDP-choline has also been shown to be effective as co-therapy for Parkinson's disease. No serious side effects have been found in any of the groups of patients treated with CDP-choline, which demonstrates the safety of the treatment.
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Methods Find Exp Clin Pharmacol · Sep 1994
ReviewSelective activation of anticancer prodrugs by monoclonal antibody-enzyme conjugates.
Several recent reports have demonstrated that anticancer drugs can be generated site-selectively at solid tumors by monoclonal antibody-enzyme conjugates targeted to antigens on tumor cell surfaces. The first step in this drug targeting approach involves the delivery of the enzyme conjugate to a tumor cell population. After the conjugate has localized within the tumor and cleared from non-target tissues, a relatively non-cytotoxic drug precursor (prodrug) is administered. ⋯ In another example involving targeted cytosine deaminase for the generation of 5-fluorouracil, it is shown that as much as 17 times more drug can be delivered within a tumor compared to when 5-fluorouracil is administered alone. The method of using targeted enzymes for prodrug activation can be extended to include prodrugs that release very potent drugs, such as palytoxin, a marine natural product, and to treat cells that have the multidrug resistance phenotype. Some of the requirements for successful therapy with this approach for cancer therapy are discussed.
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The screening and evaluation procedures for the development of anticancer agents indicated that the entire process is a rather difficult task. This is particularly true in choosing screening models and criteria for activity. If the criteria were set too low, then some clinically false-positive results may be faced; and if the criteria were set too high, some agents could be missed which might be effective against certain types of human cancer. ⋯ The time required for evaluation and development from the first discovery of activity to final FDA approval for fifty-two therapeutic drugs are tabled. The average interval is 8.8 years, but in the 1950s the average was only 2.8 years, in the 1960s, 6.5 years; in the 1970s, 13.9 years; and in the 1980s, 16.0 years. This reflects the increasing stricter requirements for an antineoplastic drug to be officially recognize