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- Brix-Christensen, V., et al.
(author)
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Plasma cytokines do not reflect expression of pro- and anti-inflammatory cytokine mRNA at organ level after cardiopulmonary bypass in neonatal pigs.
- 2003
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 47:5, s. 525-531
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Journal article (peer-reviewed)abstract
- Background: Plasma concentrations of inflammatory markers are increased in response to the trauma of cardiac surgery and cardiopulmonary bypass (CPB). It is, however, unknown whether the plasma cytokine levels and cytokine mRNA expression at organ level reflect each other. Methods: Twenty-six piglets (17–19 days) were allocated to the sham-group (sternotomy only, n = 13) or to the CPB-group (sternotomy, 120 min CPB procedure with 60-min aortic cross-clamp, n = 13). The pigs were observed for 0.5 h or 4 h post-CPB. Plasma levels of IL-1β, IL-6, IL-8 and IL-10 and mRNA expression of TNF-α, IL-1β, IL-6, IL-8, IL-10 and iNOS in organs were registered with concomitant changes in oxygenation index (OI) and expiratory nitric oxide (NO). Results: In pigs killed 0.5 h post-CPB there was a significant increase in IL-10 mRNA in the lungs and kidneys compared with the sham-group. IL-1β mRNA was detectable in the kidneys and lungs of the CPB-pigs, while IL-6 mRNA was up regulated only in lungs. In pigs killed 4 h post-CPB a significantly higher IL-6 mRNA was found in heart tissue and a lower IL-10 mRNA was found in lungs of CPB pigs compared with the sham-group. There was a concomitant significant increase in OI and increased plasma IL-8 and IL-10 concentrations in the CPB-pigs compared with the sham-pigs. Conclusion: The cytokine mRNA expression pattern was very different for the pigs killed already 0.5 h after the CPB procedure compared with the pigs killed 4 h post-CPB. The plasma cytokine levels poorly reflected mRNA expression of the pro- and anti-inflammatory cytokines.
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| 2. |
- Barklin, A, et al.
(author)
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Does brain death induce a pro-inflammatory response at the organ level in a porcine model?
- 2008
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 52:5, s. 621-627
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Journal article (peer-reviewed)abstract
- Background: Organs from brain-dead donors have a poorer prognosis after transplantation than organs from living donors. A possible explanation for this is that brain death might initiate a systemic inflammatory response, elicited by a metabolic stress response or brain ischemia. The aim of this study was to investigate the effect of brain death on the cytokine content in the heart, liver, and kidney. In addition, the metabolic and hemodynamic response caused by brain death was carefully registered. Methods: Fourteen pigs (35–40 kg) were randomized into two groups (1) eight brain-dead pigs and (2) six pigs only sham operated. Brain death was induced by inflation of an epidurally placed balloon. Blood samples for insulin, glucose, catecholamine, free fatty acids (FAA), and glucagon were obtained during the experimental period of 360 min. At the conclusion of the experiment, biopsies were taken from the heart, liver, and kidney and were analyzed for cytokine mRNA and proteins [tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-10). Results: We found a dramatic response to brain death on plasma levels of epinephrine (P=0.004), norepinephrine (P=0.02), FAA (P=0.0001), and glucagon (P=0.0003) compared with the sham group. There was no difference in cytokine content in any organ between the groups. Conclusion: In this porcine model, brain death induced a severe metabolic response in peripheral blood. At the organ level, however, there was no difference in the cytokine response between the groups.
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| 5. |
- Koefoed-Nielsen, J, et al.
(author)
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Maximal hysteresis : a new method to set positive end-expiratory pressure in acute lung injury?
- 2008
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 52:5, s. 641-649
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Journal article (peer-reviewed)abstract
- Background: No methods are superior when setting positive end-expiratory pressure (PEEP) in acute lung injury (ALI). In ALI, the vertical distance (hysteresis) between the inspiratory and expiratory limbs of a static pressure–volume (PV) loop mainly indicates lung recruitment. We hypothesized that PEEP set at the pressure where hysteresis is 90% of its maximum (90%MH) would give similar oxygenation, but less cardiovascular depression than PEEP set at the pressure at lower inflection point (LIP) on the inspiratory limb or at the point of maximal curvature (PMC) on the expiratory limb in ALI. Methods: In 12 mechanically ventilated pigs, ALI was induced in a randomized fashion by lung lavage, lung lavage plus injurious ventilation, or by oleic acid. From a static PV loop obtained by an interrupted low-flow method, the pressures at LIP [25 (25, 25) cmH2O, mean and 25, 75 percentiles], at PMC [24 (20, 24) cmH2O], and at 90% MH [19 (18, 19) cmH2O] were determined and used for the PEEP-settings. We measured lung inflation (by computed tomography), end-expiratory lung volume (EELV), airway pressures, compliance of the respiratory system (Crs), blood gases, cardiac output and arterial blood pressure. Results: There were no differences between the PEEP settings in EELV or oxygenation, but the 90%MH setting gave lower end-inspiratory pause pressure (P<0.025), higher Crs (P<0.025), less hyper-aeration (P<0.025) and better maintained hemodynamics. Conclusion: In this porcine lung injury model, PEEP set at 90% MH gave better lung mechanics and hemodynamics, than PEEP set at PMC or LIP.
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| 6. |
- Parish, CL, et al.
(author)
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Wnt5a-treated midbrain neural stem cells improve dopamine cell replacement therapy in parkinsonian mice
- 2008
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In: Journal of Clinical Investigation. - 0021-9738. ; 118:1, s. 149-160
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Journal article (peer-reviewed)abstract
- Dopamine (DA) cell replacement therapy in Parkinson disease (PD) can be achieved using human fetal mesencephalic tissue; however, limited tissue availability has hindered further developments. Embryonic stem cells provide a promising alternative, but poor survival and risk of teratoma formation have prevented their clinical application. We present here a method for generating large numbers of DA neurons based on expanding and differentiating ventral midbrain (VM) neural stem cells/progenitors in the presence of key signals necessary for VM DA neuron development. Mouse VM neurospheres (VMNs) expanded with FGF2, differentiated with sonic hedgehog and FGF8, and transfected with Wnt5a (VMN-Wnt5a) generated 10-fold more DA neurons than did conventional FGF2-treated VMNs. VMN-Wnt5a cells exhibited the transcriptional and biochemical profiles and intrinsic electrophysiological properties of midbrain DA cells. Transplantation of these cells into parkinsonian mice resulted in significant cellular and functional recovery. Importantly, no tumors were detected and only a few transplanted grafts contained sporadic nestin-expressing progenitors. Our findings show that Wnt5a improves the differentiation and functional integration of stem cell-derived DA neurons in vivo and define Wnt5a-treated neural stem cells as an efficient and safe source of DA neurons for cell replacement therapy in PD.
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