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Archives for: June 2010
03:27:03 pm, by Tom, 744 words, 1284 views
A step closer to new EU directive on animal research
Those of you who have been following the Pro-Test blog for a while will be aware that European Union (EU) is in the process of replacing Directive 86/609, the directive that covers the "laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes" with a new directive that better reflects the current state of the art of medical research and expected future developments, and does more to harmonize the regulations governing animal research in individual EU member states.
The proposed new directive on animal research was drafted by the European Commission in December 2008 and then sent to the European Parliament for its first reading. In common with the overwhelming majority of medical researchers in the EU we had grave concerns about some aspects of the proposed directive. Fortunately just before the June 2009 European elections, the EU parliament adopted a long list of amendments that it wanted incorporated, resolving many of the worries we had about the potential impact of the new directive on medical research in the EU. We were particularly pleased to see that the amendments protected the use of non-human primates in basic research, as these animals are of critical importance to fields such as neuroscience and virology.
This would usually have been sent to the European Council, a body that represents the governments of the individual EU member states, for them to give the proposal its first reading. However, to speed matters along, the Council initiated a trialogue procedure, in which representatives of the three parts of the EU legislature - the Commission, the Parliament and Council - hold private meetings to reach agreement on the text of the proposed directive.
The trialogue reached agreement on the text by December 2009, apart from a few details of committee procedure which needed to be clarified by legal experts, in the light of changes required by the Lisbon Treaty that entered into force on 1 December 2009. This agreement was marked by a formal letter from the European Parliament to the Council.
The clarification of the committee procedure points, followed by the legal checking of the text took until May, after which the Council agreed the text on 11 May and formally adopted it last week on 3 June.
We believe that the agreed directive strikes an excellent balance between the need to ensure that animals used in medical research are treated humanely, and the need to develop new treatments for terrible diseases and ensure that the EU remains at the forefront of medical science.
The next stage is that the draft directive will be sent back to the European Parliament for its second reading. Since the text is subject to a formal trialogue agreement this should be relatively swift and may involve as little as one vote in favour in the Agriculture Committee this summer and another at a plenary session of the full EU parliament probably in early autumn. At that point the Directive would be formally adopted into EU law.
The adoption of the new directive by the EU council is excellent news, and represents one more step on the long and winding road towards an EU directive on animal research that we can all be proud of.
02:29:04 pm, by Tom, 886 words, 520 views
Septic shock: Mice show way to a new treatment
When we think of the immune system we usually think of the adaptive immune system - the B-cells and T-cells that recognize and destroy specific pathogens – which isn’t surprising since this is the arm of the immune system that vaccines are designed to stimulate. However working alongside the adaptive immune system is the innate immune system which protects us form infection in a non-specific fashion. Key to this system are phagocytes, a diverse set of cells whose primary characteristic is their ability to consume and digest invading microorganisms and secrete a range of chemical messengers known as the proinflammatory cytokines which stimulate other components of the immune system. This usually a useful part of the immune response, but sometimes there is an excessive release of cytokines which causes the patient to enter a condition known as septic shock where the immune system over-reacts and causes serious tissue damage, eventually leading multiple organ failure. As a consequence of the increase in complicated surgery, implantable medical devices, elderly patients and patients with weakened immune systems, there has been an increase in the incidence of septic shock in recent years, and with around half of septic shock cases proving fatal it is now the number one cause of death in intensive care units.
This week a multinational team of scientists based in Bern, Frankfurt, Glasgow and Singapore, and led by University of Glasgow physician Professor Alirio Melendeza, have published a paper in Science (1) announcing an important development in the struggle to reduce the death rate from septic shock.
They had previously used in vitro cell culture techniques to identify an enzyme called sphingosine kinase 1 (SphK1) in human phagocytes and demonstrated using both RNAi and a specific inhibitor of SphK1 called 5c that SphK1 was involved in stimulating the cellular signaling pathways that promote release of proinflammatory cytokines. In this study they began by examining phagocytes isolated from 30 septic shock patients, finding that SphK1 levels were higher in these patients than in a control group. They next found that treating the phagocytes from septic shock patients with the inhibitor 5c blocked the production of proinflammatory cytokines by these cells in response to exposure to bacterial lipopolysaccharide, a molecule found on the exterior of some bacteria that usually provokes a strong inflammatory response.
The ability of 5c to block SphK1 dependent inflammation in-vitro was impressive but would the same happen in a whole organism where other pathways might promote inflammation? The team led by Professor Melendez next examined if 5c or RNAi could protect mice which were injected with an otherwise lethal dose of lipopolysaccharide, and they found that both methods of blocking the action of SphK1 did indeed provide complete protection against septic shock.
This was a very exciting result but acute, one-off exposure to lipopolysaccharide in vitro or in vivo is not the same as bacterial infection, where bacteria are multiplying and constantly interacting with the immune system to induce inflammation. Of course it is also vital that when turning down the inflammatory response the treatment doesn’t also compromise the immune system’s ability to fight the infection. The team therefore assessed whether pre-treatment with 5c or RNAi could prevent systemic inflammation and mortality from septic shock in a mouse model that simulates microbial infection in humans following surgery or injury, and not only was the immune system’s ability to combat the infection not compromised but the infection was cleared more quickly.
Pre-treatment is all very well but in the clinic treatment almost always starts after sepsis develops, so it was cheering to note that the inhibitor 5c reduced mortality when given up to 12 hours after infection it reduced mortality from septic shock, though it was most effective when given within 6 hours. This was as effective as the broad-spectrum the antibiotic co-amoxiclav, a standard treatment for sepsis, and when co-amoxiclav was administered along with 5c the combination was observed to be considerably more effective than either treatment used alone.
Professor Melendeza and his colleagues have identified an exciting new approach to reducing the toll from septic shock, hopefully work is already underway to translate this promising study from the bench to the bedside.
In other news the 2010 Kavli Prize in Neuroscience has gone to three scientists, Richard H. Scheller, Thomas C. Südhof, and James E. Rothman, who have “used a creative multidisciplinary set of approaches to elucidate the key molecular events of neurotransmitter release”. Their work, which involved the study of tissues from a variety of species including rats and marine rays and studies of knockout mice, has made a huge contribution to our understanding of how the release of the molecules that carry messages between the cells of the immune system work. This research may sit squarely in the realm of basic science, but the understanding of nerve cell communication that these three scientists have provided is now informing the development of new therapies for a wide range of psychiatric and neurological disorders.
Both these news items may at first seem unrelated, but what they have in common is animal research at the heart of a multidisclipinary approach that is increasingly typical of how biomedical science is done in the 21st century.
1) Puneet P. et al. "SphK1 Regulates Proinflammatory Responses Associated with Endotoxin and Polymicrobial Sepsis" Science Volume 328(5983), pages 1290 - 1294 (2010) DOI:10.1126/science.1188635
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