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JLUpub ist das institutionelle Repositorium der Justus-Liebig-Universität.
JLUpub bietet Mitgliedern und Angehörigen der Universität die Möglichkeit neben wissenschaftlichen Dokumenten auch Forschungsdaten elektronisch zu veröffentlichen und dauerhaft zugänglich zu machen. Alle Veröffentlichungen erhalten einen Digital Object Identifier (DOI) und werden über nationale und internationale Bibliothekskataloge sowie Suchmaschinen nachgewiesen und auffindbar.
Neue Veröffentlichungen:
The Role of the Kinin System and the Effect of Des-Arginine9-Bradykinin on Coagulation and Platelet Function in Critically Ill COVID-19 Patients: A Secondary Analysis of a Prospective Observational Study
(2024) Edinger, Fabian; Edinger, Sophia; Schmidt, Götz; Koch, Christian; Sander, Michael; Schneck, Emmanuel
The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the coagulation system is not fully understood. SARS-CoV-2 penetrates cells through angiotensin-converting enzyme 2 (ACE2) receptors, leading to its downregulation. Des-arginine9-bradykinin (DA9B) is degraded by ACE2 and causes vasodilation and increased vascular permeability. Furthermore, DA9B is associated with impaired platelet function. Therefore, the aim of this study was to evaluate the effects of DA9B on platelet function and coagulopathy in critically ill coronavirus disease 2019 (COVID-19) patients. In total, 29 polymerase-positive SARS-CoV-2 patients admitted to the intensive care unit of the University Hospital of Giessen and 29 healthy controls were included. Blood samples were taken, and platelet impedance aggregometry and rotational thromboelastometry were performed. Enzyme-linked immunosorbent assays measured the concentrations of DA9B, bradykinin, and angiotensin 2. Significantly increased concentrations of DA9B and angiotensin 2 were found in the COVID-19 patients. A negative effect of DA9B on platelet function and intrinsic coagulation was also found. A sub-analysis of moderate and severe acute respiratory distress syndrome patients revealed a negative association between DA9B and platelet counts and fibrinogen levels. DA9B provokes inhibitory effects on the intrinsic coagulation system in COVID-19 patients. This negative feedback seems reasonable as bradykinin, which is transformed to DA9B, is released after contact activation. Nevertheless, further studies are needed to confirm our findings.
A Novel Rat Model of Mild Pulmonary Hypertension Associated with Pulmonary Venous Congestion Induced by Left Pulmonary Vein Banding
(2024) Münks, Jonas; Yogeswaran, Athiththan; Antoine, Tobiah Kevin; Blumrich, Leonhard Anton; Dorfmüller, Peter; Ghofrani, Hossein Ardeschir; Assmus, Birgit; Schermuly, Ralph Theo; Sydykov, Akylbek
Pulmonary hypertension (PH) associated with left heart disease (PH-LHD) is the most common form of PH. In PH-LHD, changes in the pulmonary vasculature are assumed to be mainly caused by pulmonary venous congestion. However, the underlying mechanisms of this form of PH are poorly understood. We aimed to establish a model of PH associated with pulmonary venous congestion. Wistar–Kyoto rats underwent partial occlusion of the left pulmonary vein to induce pulmonary venous congestion or sham surgery and were assessed at various time points post-surgery (3, 6, 9, 12 weeks). In vivo cardiopulmonary phenotyping was performed by using echocardiography along with heart catheterization. Histomorphometry methods were used to assess pulmonary vascular remodeling (e.g., wall thickness, degree of muscularization). Left pulmonary vein banding (PVB) resulted in mildly elevated right ventricular systolic pressure and moderate right ventricular hypertrophy. In PVB rats, small- and medium-sized pulmonary vessels in the left lung were characterized by increased wall thickness and muscularization. Taken together, our data demonstrate that left PVB-induced pulmonary venous congestion is associated with pulmonary vascular remodeling and mild PH.
Occlusal Caries Detection with Intraoral Scanners in Pediatric Dentistry: A Comparative Clinical Study
(2024) Schulz-Weidner, Nelly; Gruber, Marina; Wöstmann, Bernd; Uebereck, Constanze Friederike; Krämer, Norbert; Schlenz, Maximiliane Amelie
Background: The aim of this clinical study was to compare the occlusal caries detection (OCD) performance of the intraoral scanners (IOSs) Trios 4 (TIO, 3Shape) and Emerald S (EME, Planmeca) and the Diagnocam (DIA, KaVo) with the established visual (WHO) examination (VIS, reference method).
Methods: Between 08/2022 and 02/2023, 60 children (mean age 9.6 ± 2.5 years) were examined as part of their regular dental checkups. OCD was performed at the tooth level, separately for primary and permanent unrestored teeth. Furthermore, two thresholds were analyzed: sound versus overall caries (pooled data of enamel and dentin caries, TH1) and pooled data of sound and enamel caries versus dentin caries (TH2).
Results: The best agreement with the reference method (reliability) in both dentitions was obtained for DIA (ĸ = 0.829/ĸ = 0.846; primary/permanent teeth), followed by EME (ĸ = 0.827/ĸ = 0.837) and TIO (ĸ = 0.714/ĸ = 0.680). Similar results were shown for the diagnostic quality (sensitivity, specificity and area under the curve of the receiver operating characteristic curve), with higher values for TH1 than for TH2. Both IOSs and the DIA showed worse results than the reference method VIS.
Conclusions: Currently, IOS should be used as an additional caries detection tool, especially for visualization, and cannot be recommended as a basic tool for diagnosis or invasive/noninvasive therapy decisions in OCD.
Cathelicidin Antimicrobial Peptide Levels in Atherosclerosis and Myocardial Infarction in Mice and Human
(2024) Höpfinger, Alexandra; Schmid, Andreas; Karrasch, Thomas; Pankuweit, Sabine; Schäffler, Andreas; Grote, Karsten
Obesity represents a worldwide health challenge, and the condition is accompanied by elevated risk of cardiovascular diseases caused by metabolic dysfunction and proinflammatory adipokines. Among those, the immune-modulatory cathelicidin antimicrobial peptide (human: CAMP; murine: CRAMP) might contribute to the interaction of the innate immune system and metabolism in these settings. We investigated systemic CAMP/CRAMP levels in experimental murine models of atherosclerosis, myocardial infarction and cardiovascular patients. Atherosclerosis was induced in low-density lipoprotein receptor-deficient (Ldlr−/−) mice by high-fat diet (HFD). C57BL/6J wild-type mice were subjected to myocardial infarction by permanent or transient left anterior descending (LAD)-ligation. Cramp gene expression in murine organs and tissues was investigated via real-time PCR. Blood samples of 234 adult individuals with or without coronary artery disease (CAD) were collected. Human and murine CAMP/CRAMP serum levels were quantified by ELISA. Atherosclerotic mice exhibited significantly increased CRAMP serum levels and induced Cramp gene expression in the spleen and liver, whereas experimental myocardial infarction substantially decreased CRAMP serum levels. Human CAMP serum quantities were not significantly affected by CAD while being correlated with leukocytes and pro-inflammatory cytokines. Our data show an influence of cathelicidin in experimental atherosclerosis, myocardial infarction, as well as in patients with CAD. Further studies are needed to elucidate the pathophysiological mechanism.
The CD177 c.1291A Allele Leads to a Loss of Membrane Expression and Mimics a CD177-Null Phenotype
(2024) Traum, Annalena; Jehle, Stefanie; Waxmann, Yannick; Litmeyer, Anne-Sophie; Berghöfer, Heike; Bein, Gregor; Dammann, Reinhard; Perniss, Alexander; Burg-Roderfeld, Monika; Sachs, Ulrich J.; Bayat, Behnaz
CD177 is a glycosyl phosphatidyl inositol (GPI)-linked, neutrophil-specific glycoprotein that in 3–5% of normal individuals is absent from all neutrophils. The molecular mechanism behind the absence of CD177 has not been unravelled completely. Here, we analyse the impact of the recently described CD177 c.1291G>A variant on CD177 expression. Recombinant CD177 c.1291G>A was expressed in HEK293F cells and its expression on the cell surface, inside the cell, and in the culture supernatant was investigated. The CD177 c.1291G>A protein was characterised serologically and its interaction with proteinase 3 (PR3) was demonstrated by confocal laser scanning microscopy. Our experiments show that CD177 c.1291G>A does not interfere with CD177 protein biosynthesis but affects the membrane expression of CD177, leading to very low copy numbers of the protein on the cellular surface. The mutation does not interfere with the ability of the protein to bind PR3 or human polyclonal antibodies against wild-type CD177. Carriers of the c.1291G>A allele are supposed to be phenotyped as CD177-negative, but the protein is present in soluble form. The presence of CD177 c.1291A leads to the production of an unstable CD177 protein and an apparent “CD177-null” phenotype.