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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The reasons reduction and replacement of laboratory animals are advancing rapidly in basic biomedical research, and why in industrial toxicology progress is much slower, are analyzed. Reference is made to a previous report from our laboratory, and the general concept of the program is outlined. Encouraging developments concerning acceptance of new concepts in acute toxicity testing by various regulatory agencies are reviewed (OECD, IKS, EEC, and Bureau of Pharmaceutical Affairs, Ministry of Health and Welfare, Japan). On the basis of new concepts proposed by the British Toxicology Society, a program which attempts to evaluate acute toxicity of chemicals as far as possible without causing mortality was started. Continuous in-cage monitoring of motility of animals, regular control of general health, body weight, food and water consumption, and body temperature are used as variables. The possibilities of reducing animal use in toxicology by application of toxicological screening procedures are explained. Screening tests under development include an operant conditioning technique to detect adverse drug interactions with ethanol and a procedure for the detection of nephrotoxic properties. The successful completion of a collaborative program designed to upgrade toxicity testing with contraceptive steroids and to abolish the 7-year beagle and 10-year monkey studies is reported. The application of in vitro cytotoxicity tests for assessment of irritant and corrosive properties of chemicals is discussed and some encouraging progress on regulatory acceptance of such tests (OECD) is reported. A new test developed at the institute is described. An in vitro model for the investigation of chemically induced changes of collagen synthesis in human fibroblasts is presented. Other cell culture methods under development include a culture system of chick brain, retina, and menings cells for the study of neurotoxic chemicals and neurobehavioral teratogens, primary hepatocyte cultures for the study of drug effects on DNA and protein synthesis and ploidy, using flow cytometry, and various in vitro models for the assessment of genotoxic and tumor-promoting activities and malignant cell transformation. The problem of analgesic treatment of animals with chronic pain was investigated. Several analgesics were evaluated, and treatment modalities providing demonstrable analgesia for prolonged periods of time in mice and rats were worked out.
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PMID:Reduction and replacement of laboratory animals in toxicological testing and research. Interim report 1984-1987. 307 63

Poly(butylcyanoacrylate) nanoparticles were produced by emulsion polymerisation and used either uncoated or overcoated with polysorbate 80 (Tween 80). [3H]-dalargin bound to nanoparticles overcoated with polysorbate 80 or in the form of saline solution was injected into mice and the brain concentrations of radioactivity determined. Statistically significant, three-fold higher brain concentrations with the nanoparticle preparations were obtained after 45 minutes, the time of greatest pharmacological response assessed as analgesia in previous experiments. In addition the brain inulin spaces in rats and the uptake of fluoresceine isothiocyanate labelled nanoparticles in immortalised rat cerebral endothelial cells, (RBE4) were measured. The inulin spaces after i.v. injection of polysorbate 80-coated nanoparticles were significantly increased by 1% compared to controls. This is interpreted as indicating that there is no large scale opening of the tight junctions of the brain endothelium by the polysorbate 80-coated nanoparticles. In in vitro experiments endocytic uptake of fluorescent nanoparticles by RBE4 cells was only observed after polysorbate 80-overcoating, not with uncoated particles. These results further support the hypothesis that the mechanism of blood-brain barrier transport of drugs by polysorbate 80-coated nanoparticles is one of endocytosis followed by possible transcytosis. The experiments were conducted in several laboratories as part of an EEC/INTAS collaborative program. For various procedural and regulatory reasons this necessitated the use of both rats and mice as experimental animals. The brain endothelial cell line used for the in vitro studies is the rat RBE4.
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PMID:Interaction of poly(butylcyanoacrylate) nanoparticles with the blood-brain barrier in vivo and in vitro. 1169 6

It is now more than 20 years since both Council of Europe Convention ETS123 and EU Directive 86/609/EEC were introduced, to promote the implementation of the Three Rs in animal experimentation and to provide guidance on animal housing and care. It might therefore be expected that reports of the implementation of the Three Rs in animal research papers would have increased during this period. In order to test this hypothesis, a literature survey of animal-based research was conducted. A randomly-selected sample from 16 high-profile medical journals, of original research papers arising from European institutions that featured experiments which involved either mice or primates, were identified for the years 1986 and 2006 (Total sample = 250 papers). Each paper was scored out of 10 for the incidence of reporting on the implementation of Three Rs-related factors corresponding to Replacement (justification of non-use of non-animal methods), Reduction (statistical analysis of the number of animals needed) and Refinement (housing aspects, i.e. increased cage size, social housing, enrichment of cage environment and food; and procedural aspects, i.e. the use of anaesthesia, analgesia, humane endpoints, and training for procedures with positive reinforcement). There was no significant increase in overall reporting score over time, for either mouse or primate research. By 2006, mouse research papers scored an average of 0 out of a possible 10, and primate research papers scored an average of 1.5. This review provides systematic evidence that animal research is still not properly reported, and supports the call within the scientific community for action to be taken by journals to update their policies.
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PMID:Reporting the implementation of the Three Rs in European primate and mouse research papers: are we making progress? 2127 72