Background: Pure autonomic failure (PAF) and multiple system atrophy (MSA) are rare disorders causing severe autonomic failure. Their initially similar clinical presentation may lead to years of... Show moreBackground: Pure autonomic failure (PAF) and multiple system atrophy (MSA) are rare disorders causing severe autonomic failure. Their initially similar clinical presentation may lead to years of diagnostic difficulties. Improving the differentiation would have an important impact on patients and families in view of better prediction of disease progression. Objective: To investigate whether several new non-invasive autonomic tests are beneficial in discriminating between PAF and MSA. Methods: Patients and controls underwent two tests examining the autonomic innervation of the skin (Sudoscan and water-induced skin wrinkling) and one test measuring retinal nerve fiber layer thickness in the eye. Results: The skin vasomotor tests yielded differences between the disease and control groups, but did not discriminate between PAF and MSA. No differences in retinal nerve fiber layer thickness were found between the groups. Conclusion: The tests applied in this study may help to confirm autonomic failure but did not support the differential diagnosis between PAF and MSA. Show less
Ischemia-reperfusion injury (IRI) is a pathophysiological event that occurs in many clinical conditions, ranging from surgery, acute artery occlusion to transplantation. Complement activation is... Show moreIschemia-reperfusion injury (IRI) is a pathophysiological event that occurs in many clinical conditions, ranging from surgery, acute artery occlusion to transplantation. Complement activation is thought to be a crucial step in IRI, because complement inhibition and complement deficiency considerably attenuate irreversible injury. However, the specific complement pathway remains unclear. All three complement pathways: the classical, the alternative, and the mannose-binding lectin dependent pathway may be involved in the development of IRI, depending on the model, the tissue, and the time course of inflammation. Ischemia leads to the exposition of neoantigens on the jeopardized tissues, which could be recognized by C-reactive protein (CRP) and natural IgM antibodies. The binding of CRP and IgM to these neoepitopes is followed by complement activation. In this thesis, we demonstrated that both proteins bind to jeopardized tissues and activate the complement system, in particular intestines from rats subjected to IRI. Furthermore, it was shown that IgM levels against altered phospholipids correlated with the levels of inflammatory mediators in patients subjected to tissue damage suggesting that IgM participates in amplification of inflammation. The development of strategies to prevent binding of CRP and/or IgM is an attractive approach for a therapy for reducing IRI. Show less
