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Aachen, Germany

Albrecht M.,University of Kiel | Meybohm P.,University Hospital Frankfurt | Broch O.,University of Kiel | Zitta K.,University of Kiel | And 5 more authors.
Resuscitation | Year: 2015

Background: Remote ischaemic post-conditioning (RIPoC) in which transient episodes of ischaemia (e.g. by inflation and deflation of a blood pressure cuff) are applied after a prolonged ischaemia/reperfusion injury, may have the potential to improve patient outcome and survival following cardiac arrest. In this study we employed a pig model of cardiac arrest and successful cardiopulmonary resuscitation to evaluate the effects of RIPoC on haemodynamics, cardiac tissue damage and neurologic deficit. Materials and methods: A total of 22 pigs were subjected to ventricular fibrillation, cardiopulmonary resuscitation and randomly assigned to Control or RIPoC treatment consisting of 4 cycles of 5. min femoral artery occlusion followed by 5 min of reperfusion starting 10. min after return of spontaneous circulation (ROSC). Post-resuscitation was evaluated by haemodynamics using left ventricular conductance catheters, quantification of cardiac troponin T (cTnT), lactate dehydrogenase (LDH) and creatine kinase (CK). Neurological testing was performed 24 h after return of spontaneous circulation (ROSC). Results: RIPoC resulted in a statistically significant reduction of serum cTnT levels 4 h after ROSC (P≤ 0.01). LDH and CK concentrations were significantly lower in RIPoC treated pigs 24 h after ROSC (P≤ 0.001), suggesting tissue and/or cardioprotective effects of RIPoC. End-systolic pressure volume relationship was significantly increased in RIPoC treated animals 4 h after ROSC (P≤ 0.05). Neurological testing revealed a trend towards an improved outcome in RIPoC treated animals. Conclusions: We propose that RIPoC applied immediately after ROSC reduces serum concentrations of markers for cell damage and improves end-systolic pressure volume relationship 4 h after ROSC. © 2015 Elsevier Ireland Ltd. Source

Liu Z.,RWTH Aachen | Lammers T.,RWTH Aachen | Ehling J.,RWTH Aachen | Ehling J.,University Hospital Aachen | And 4 more authors.
Biomaterials | Year: 2011

Magnetic resonance (MR) and ultrasound (US) imaging are widely used diagnostic modalities for various experimental and clinical applications. In this study, iron oxide nanoparticle-embedded polymeric microbubbles were designed as multi-modal contrast agents for hybrid MR-US imaging. These magnetic nano-in-micro imaging probes were prepared via a one-pot emulsion polymerization to form poly(butyl cyanoacrylate) microbubbles, along with the oil-in-water (O/W) encapsulation of iron oxide nanoparticles in the bubble shell. The nano-in-micro embedding strategy was validated using NMR and electron microscopy. These hybrid imaging agents exhibited strong contrast in US and an increased transversal relaxation rate in MR. Moreover, a significant increase in longitudinal and transversal relaxivities was observed after US-induced bubble destruction, which demonstrated triggerable MR imaging properties. Proof-of-principle in vivo experiments confirmed that these nanoparticle-embedded microbubble composites are suitable contrast agents for both MR and US imaging. In summary, these magnetic nano-in-micro hybrid materials are highly interesting systems for bimodal MR-US imaging, and their enhanced relaxivities upon US-induced destruction recommend them as potential vehicles for MR-guided US-mediated drug and gene delivery. © 2011 Elsevier Ltd. Source

Martin I.V.,University Hospital Aachen | Martin I.V.,University of Zurich | Martin I.V.,RWTH Aachen | Schmitt J.,University of Zurich | And 6 more authors.
Biological Chemistry | Year: 2010

The nuclear bile acid receptor FXR (farnesoid-X-receptor) has recently been implicated in the pathophysiology of nonalcoholic fatty liver disease because selective FXR-agonists improve glucose and lipid metabolism in rodent models of obesity. However, the regulation of FXR and other relevant nuclear receptors as well as their lipogenic target genes in fatty liver is still not revealed in detail. Livers were harvested from 14-week-old male ob/ob mice and wild-type controls. Serum bile acids were quantified by radioimmunoassay. mRNA and protein expression of transporters and nuclear receptors was analyzed by reverse transcriptase-polymerase chain reaction and Western blotting, whereas DNA binding to the IR-1 element was examined by electrophoretic mobility shift assay. In this study we show: (i) bile acid retention in ob/ob mice, (ii) a resulting FXR upregulation and binding to the IR-1 element in ob/ob animals and (iii) concomitant activation of the fatty acid synthase as a potential lipogenic FXR target gene in vivo. The present study suggests a potential role of hepatic bile acid retention and FXR activation in the induction of lipogenic target genes. Differences between intestinal and hepatic FXR could explain apparent contradictory information regarding its effects on fatty liver disease. © by Walter de Gruyter Berlin New York. Source

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