| 1. |
- Forsberg, Kalle, et al.
(författare)
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A Systematic Review Of Erythropoietin In Experimental Stroke
- 2009
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Ingår i: Stroke. - 0039-2499. ; 40:4
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Konferensbidrag (refereegranskat)abstract
- Introduction: Erythropoietin (EPO), a hematopoietic growth factor, has promise as a neuroprotectant in animal models of ischemic stroke. EPO is thought not only to protect neurons from cell death, but also is hypothesized to promote regeneration post stroke. Here we report a systematic review and meta-analysis of the published animal data characterizing the efficacy of EPO. Methods We conducted a systematic review and random effects weighted mean difference meta-analysis only including studies describing the efficacy of EPO in models of focal cerebral ischemia. Primary outcomes were infarct size and neurobehavioral score. A stratified analysis to identify the impact of elements of study quality and design was also conducted. Results Only 11 of 943 studies met our inclusion criteria. Infarct size was reported in 15 experiments using 191 animals. Neurobehavioral score was reported in 16 experiments using 287 animals. EPO improved infarct size by 30.5% (95%Cl 19.3%-41.7%) and neurobehavioral score by 37.4% (31.2– 43.7%). For infarct size, EPO was least effective in thrombotic models of ischemia, (16% versus to 44.8% and 24% in permanent and transient models of ischemia respectively, X2 =1.47 x 10–04). Using a scoring system derived from the STAIR criteria,study quality was modest with a median score of 4 out of 11 for both outcomes. Studies that randomized to treatment group reported smaller infarct sizes compared to those that did not (18.0% versus 44.8%, n=113 versus 78 animals, X2 = 3.4 x 10–05). Studies that blinded assessment of outcome also showed a smaller improvement in neurobehavioral score (31.1% versus 41.6%, n=107 versus 167, X2 = 8.9 x 10–4). Only 11.7% of the animals in the total dataset had a co-morbidity common to human stroke (hypertension) and this co-morbidity was only reported for neurobehavioral comparisons, not for infarct size. Blinded induction of ischemia was reported in 2 experiments (21.5% of animals) measuring infarct volume. Conclusions: Aggregation of the animal data for EPO in ischemic stroke indicates mean effect sizes of 30.5% and 37.4% for infarct volume and neurobehavioral score respectively. However, when the impact of common sources of bias are considered these effect sizes fall suggesting we are overestimating its potential benefit. As common human co-morbidities may reduce therapeutic efficacy, broader testing to delineate the range of circumstances in which EPO works would be beneficial before clinical trialing.
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| 2. |
- Douglas, Andrew, et al.
(författare)
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Platelet-rich emboli are associated with von Willebrand factor levels and have poorer revascularization outcomes.
- 2020
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Ingår i: Journal of neurointerventional surgery. - : BMJ. - 1759-8486 .- 1759-8478. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Platelets and von Willebrand factor (vWF) are key factors in thrombosis and thus are likely key components of acute ischemic stroke (AIS) emboli. We aimed to characterize platelet and vWF levels in AIS emboli and to assess associations between their expression levels and clinical and procedural information.Histopathological and immunohistochemical analysis of emboli collected as part of the multi-institutional RESTORE registry was performed. The composition of the emboli was quantified using Orbit Image Analysis machine learning software. Correlations between clot components and clinical and procedural information were assessed using the χ2 test.Ninety-one emboli samples retrieved from 63 patients were analyzed in the study. The mean platelet (CD42b) content of the clots was 33.9% and the mean vWF content of the clots was 29.8%. There was a positive correlation between platelet and vWF levels (ρ=0.564, p<0.001*, n=91). There was an inverse correlation between both platelets and vWF levels and percentage of red blood cells (RBCs) in the emboli (CD42b vs RBC: ρ=-0.535, p<0.001*, n=91; vWF vs RBC: ρ=-0.366, p<0.001*, n=91). Eighty-one percent of patients in the low platelet group had a good revascularization outcome (Thrombolysis in Cerebral Infarction 2c/3) compared with 58% in the high platelet group (χ2=5.856, p=0.016).Platelet and vWF levels in AIS emboli correlate with each other and both have an inverse relationship with RBC composition. Patients with platelet-rich clots have poorer revascularization outcomes.
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| 3. |
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| 4. |
- Jerndal, Mikael, et al.
(författare)
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A systematic review and meta-analysis of erythropoietin in experimental stroke.
- 2010
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Ingår i: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 1559-7016. ; 30:5, s. 961-8
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Forskningsöversikt (refereegranskat)abstract
- Erythropoietin (EPO) has shown promise as a neuroprotectant in animal models of ischemic stroke. EPO is thought not only to protect neurons from cell death, but also to promote regeneration after stroke. Here, we report a systematic review and meta-analysis of the efficacy of EPO in animal models of focal cerebral ischemia. Primary outcomes were infarct size and neurobehavioral outcome. Nineteen studies involving 346 animals for infarct size and 425 animals for neurobehavioral outcome met our inclusion criteria. Erythropoietin improved infarct size by 30.0% (95% CI: 21.3 to 38.8) and neurobehavioral outcome by 39.8% (33.7 to 45.9). Studies that randomized to treatment group or that blinded assessment of outcome showed lower efficacy. Erythropoietin was tested in animals with hypertension in no studies reporting infarct size and in 7.5% of the animals reporting neurobehavioral outcome. These findings show efficacy for EPO in experimental stroke, but when the impact of common sources of bias are considered, this efficacy falls, suggesting we may be overestimating its potential benefit. As common human co-morbidities may reduce therapeutic efficacy, broader testing to delineate the range of circumstances in which EPO works best would be beneficial.
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| 5. |
- Jerndal, Mikael, et al.
(författare)
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Systematic review and meta-analysis of the efficacy of basic fibroblast growth factor in experimental stroke
- 2009
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Ingår i: European Stroke conference, Stockholm, Sweden May.
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Konferensbidrag (refereegranskat)abstract
- Background Basic fibroblast growth factor (bFGF) has been shown to have a potent trophic effect on brain neurons, glia and endothelial cells in both in vitro and in vivo studies and is a candidate drug for treatment of ischemic stroke. Any decision to proceed to clinical trials should be based on an unbiased assessment of all available animal data. This assessment should evaluate the efficacy of the drug as well as the characteristics and limits to that efficacy. We use a systematic approach to assess the evidence for protective effects of bFGF in animal models of focal cerebral ischemia. Methods We have performed a systematic review and meta-analysis of studies describing the efficacy of bFGF in animal models of focal cerebral ischemia where outcome was measured as infarct size or neurological score. Study quality was scored against a quality checklist and certain study characteristics were looked at individually. A random effects model was used and the significance level was set to p<0.001 to allow for multiple comparisons. Results Systematic review identified 21 publications of which 20 report infarct size from 520 animals and 10 report neurological score from 223 animals. bFGF reduced infarct size by 25.7% (95% confidence interval 21.7-29.8%) and improved neurological score by 28.1% (23.0-33.2%). Efficacy was higher with intra-arterial administration which showed a reduction of infarct size by 57.6% (33.8-81.3%, p=9.8E-07). Overall study quality was moderate with a median quality score of 6/11, interquartile range 5-7. Studies that performed blinded assessment of outcome showed lesser efficacy on infarct size reduction than those who did not blind, 20.2% (12.2-28.1) compared to 29.4% (26.7-32.1%, p=0.00073). The use of animals with associated comorbidities was rare, with only 4.4% aged animals and no animals with diabetes or hypertension. Aged animals showed lower effect size with only 4.7% reduction of infarct size (-9.0-18.3%, p=1.0E-05). Conclusion Our study shows that bFGF-1 has efficacy in experimental ischemic stroke. The effect of study quality and bias limits the strength of this conclusion. Further research is needed to test the efficacy in animals with associated co morbidities.
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| 6. |
- Leion, Henrik, 1976, et al.
(författare)
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Solid fuels in chemical-looping combustion using oxide scale and unprocessed iron ore as oxygen carriers
- 2009
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Ingår i: Fuel. - 0016-2361. ; 88:10, s. 1945-1954
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Tidskriftsartikel (refereegranskat)abstract
- Chemical-looping combustion (CLC) is a novel technology that can be used to meet demands on energy production without CO2 emissions. The CLC-process includes two reactors, an air and a fuel reactor. Between these two reactors oxygen is transported by an oxygen carrier, which most often is a metal oxide. This arrangement prevents mixing of N2 from the air with CO2 from the combustion. The combustion gases consist almost entirely of CO2 and H2O. Therefore, the technique reduces the energy penalty that normally arises from the separation of CO2 from other flue gases, hence, CLC may make capture of CO2 cheaper.Iron ore and oxide scale from steel production were tested as oxygen carriers in CLC batch experiments with solid fuels. Petroleum coke, charcoal, lignite and two bituminous coals were used as fuels.The experiments were carried out in a laboratory fluidized-bed reactor that was operating cyclically with alternating oxidation and reduction phases. The exhaust gases were led to an analyzer where the contents of CO2, CO, CH4 and O2 were measured. Gas samples collected in bags were used to analyze the content of hydrogen in a gas chromatograph.The results showed that both the iron ore and the oxide scale worked well as oxygen carrier and both oxygen carriers increased their reactivity with time.
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