Oxidative damage and chemokine production dominate days before immune cell infiltration and EAE disease debut

BACKGROUND: Multiple sclerosis is widely accepted as an inflammatory disease. However, studies indicate that degenerative processes in the CNS occur prior to inflammation. In the widely used animal model experimental autoimmune encephalomyelitis (EAE), we investigated the significance of degenerative processes from mitochondrial membrane potentials, reactive oxidative species, cell death markers, chemokines, and inflammatory cell types in brain, spinal cord, and optic nerve tissue during the effector phase of the disease, before clinical disease was evident. METHODS: Sixty-two rats were placed in eight groups, n = 6 to 10. Four groups were immunized with spinal cord homogenate emulsified in complete Freund’s adjuvant (one served as EAE group), three groups were immunized with complete Freund’s adjuvant only, and a control group was injected with phosphate buffered saline only. Groups were sacrificed 3, 5, 7, or 12–13 days after the intervention and analyzed for early signs of CNS degeneration. RESULTS: Loss of mitochondrial membrane potential and oxidative changes was observed days before clinical disease debut at day 9.75 ± 0.89. The early mitochondrial changes were not associated with cytochrome C release, cleavage of caspases 9 (38/40 kDa) and 3 (17/19 kDa), and cleavage of PARP (89 kDa) or spectrin (120/150 kDa), and apoptosis was not initiated. Axonal degeneration was only present at disease onset. Increases in a range of cytokines and chemokines were observed systemically as a consequence of immunization with complete Freund’s adjuvant, whereas the encephalitogenic emulsion induced an upregulation of the chemokines Ccl2, Ccl20, and Cxcl1, specifically in brain tissue, 7 days after immunization. CONCLUSION: Five to seven days after immunization, subtle decreases in the mitochondrial membrane potential and an increased reactive oxygen species burden in brain tissue were observed. No cell death was detected at these time-points, but a specific expression pattern of chemokines indicates activity in the CNS, several days before clinical disease debut

Towards a North Sea ecosystem component of GOOS for assessment and management: report from a strategic workshop in Bergen 5-7 September 2001

ICES and IOC have established a joint Steering Group on GOOS (SGGOOS), which also involves the European component of GOOS (EuroGOOS). To increase the efficiency and effectiveness of the use of data products from current relevant national and international monitoring of the North Sea, the workshop invited the national agencies responsible for monitoring of the North Sea to: - establish a coordinated mechanism that could add value to existing activities by integrating data from various sources (physical, chemical, biological) to aid development of an ecosystem approach, - collaborate by means of a pilot project sponsored by ICES and EuroGOOS to demonstrate the usefulness of this approach by integrating data on oceanography and fisheries

Inddragelsen af "andre aktører" i beskæftigelsespolitikken

Med arbejdsmarkedsreformen Flere i arbejde er dele af arbejdsformidlingssystemet blevet udliciteret til såkaldte 'andre aktører'. Artiklen ser dette som et væsentligt nybrud i beskæftigelsespolitikken. Et nybrud, som har afgørende konsekvenser for beskæftigelsespolitikkens styring, organisering, implementering og effekter. Dette illustreres gennem en 'quasi-marked'-analyse af det 'nye' marked for jobformidling, aktivering og kvalificering samt ved en sammenligning med tilsvarende reformer i navnlig Holland og Australien. Analysen viser, at 'quasi-markedet' for beskæftigelsesindsatser skaber en række arbejdsmarkedspolitiske problemstillinger og udfordringer, som har en mere fundamental karakter end de 'børnesygdomme', der peges på i den politiske debat

The site of embolization related to infarct size, oedema and clinical outcome in a rat stroke model - further translational stroke research

<p>Abstract</p> <p>Background and purpose</p> <p>Reliable models are essential for translational stroke research to study the pathophysiology of ischaemic stroke in an effort to find therapies that may ultimately reduce oedema, infarction and mortality in the clinic. The purpose of this study was to investigate the relation between the site of arterial embolization and the subsequent oedema, infarction and clinical outcome in a rat embolic stroke model.</p> <p>Methods</p> <p>Thirty-six male Sprague-Dawley rats were thromboembolized into the internal carotid artery. The site of occlusion was demonstrated by arteriography. Following histological preparation and evaluation, the size of the hemispheres and the infarcts were measured by quantitative histology and planimetry. Another parallel stroke model study was subsequently examined to investigate if the conclusions from the first study could be applied to the second study.</p> <p>Results</p> <p>The median size of the infarct was 40% of the ipsilateral hemisphere in both the 19 animals with occlusion localised to the intracranial part of the internal carotid artery and in the 11 animals where the main trunk of the middle cerebral artery was occluded. In 5 animals, occlusion of the extracranial part of the internal carotid artery resulted in significantly smaller infarcts compared to other groups (p < 0.01). Another independent study re-confirmed these results. Furthermore, significant correlations (R > 0.76, p < 0.0001) were found between 1) cortical, subcortical, and total infarct volumes, 2) oedema in percent of the left hemisphere, 3) clinical score before termination and 4) postoperative weight loss.</p> <p>Conclusions</p> <p>Distal occlusions of the intracranial part of the internal carotid or middle cerebral arteries resulted in comparable large sized infarctions and oedema. This indicates that investigators do not need a similar number of such occlusions in each experimental group. Contrary to observations in the clinic, distal internal carotid artery occlusions did not result in worse outcome than middle cerebral stem occlusions, but this finding may be explained by the controlled emboli size in this experimental stroke model.</p