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227 Publications visible to you, out of a total of 227
Biomechanical properties of polymer-infiltrated ceramic crowns on one-piece zirconia implants after long-term chewing simulation
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND Implant and superstructure provide a complex system, which has to withstand oral conditions. Concerning the brittleness of many ceramics, fractures are a greatly feared issue. Therefore, …, polymer-infiltrated ceramic networks (PICNs) were developed. Because of its low Young’s modulus and high elastic modulus, the PICN crown on a one-piece zirconia implant might absorb forces to prevent the system from fracturing in order to sustain oral forces. Recommendations for the material of superstructure on zirconia implants are lacking, and only one study investigates PICN crowns on these types of implants. Accordingly, this study aimed to examine PICN crowns on one-piece zirconia implants regarding bond strength and surface wear after long-term chewing simulation (CS). METHODS Twenty-five hybrid ceramic crowns (Vita Enamic, Vita Zahnfabrik) were produced using computer-aided design/computer-aided manufacturing (CAD/CAM) technology and adhesively bonded (RelyX™ Ultimate, 3M ESPE) to zirconia implants. Twenty of the specimens underwent simultaneous mechanical loading and thermocycling simulating a 5-year clinical situation (SD Mechatronik GmbH). Wear depth and wear volume, based on X-ray micro-computed tomography volume scans (Skyscan 1172-100-50, Bruker) before and after CS, were evaluated. All crowns were removed from the implants using a universal testing machine (Z010, Zwick GmbH&Co.KG). Subsequently, luting agent was light microscopically localized (Stemi 2000-C, Zeiss). With a scanning electron microscope (SEM, Phenom™ G2 pro, Phenom World), the area of abrasion was assessed. RESULTS 1. After CS, none of the tested crowns were fractured or loosened. 2. The maximum vertical wear after CS was M = 0.31 \pm 0.04 mm (mean \pm standard deviation), and the surface wear was M = 0.74 \pm 0.23 mm3. 3. The pull-off tests revealed a 1.8 times higher bond strength of the control group compared to the experimental group (t(23) = 8.69, p \textless 0.001). 4. Luting agent was mostly located in the crowns, not on the implants. 5. The area of abrasion showed avulsion and a rough surface. CONCLUSIONS PICN on one-piece zirconia implants showed high bond strength and high wear after CS.

Authors: Pia Baumgart, Holger Kirsten, Rainer Haak, Constanze Olms

Date Published: 1st Dec 2018

Publication Type: Journal article

Intra-individual alterations of serum markers routinely used in forensic pathology depending on increasing post-mortem interval
Genetical Statistics and Systems Biology

Abstract (Expand)

Post-mortem biochemistry of serum markers has been the subject of numerous studies, but in-situ marker stability after death has not been sufficiently evaluated yet. Such laboratory analyses are … especially necessary in the cases of functional deaths without morphological evidence of the death causes and also in cardiac death cases with only very short survival times. The aim of the study was to determine the post-mortem stability of commonly-used serum markers at predefined time points. In 20 cases, peripheral venous samples were taken starting immediately after circulatory arrest and ending 48 hours after death. Serum creatinine, urea, 3-\textgreekb-hydroxybutyrate, tryptase, myoglobin, troponin T, creatin kinase and creatin kinase-MB have been included. For all markers, we observed increasing marker levels for longer post-mortem intervals. Significant marker level changes began two hours after death. Excessive increases were observed for cardiac and muscle markers. Marker levels showed high intra-assay precision. Furthermore, the markers were robust enough to withstand freeze-thaw cycles. Potential contamination of arteriovenous blood did not influence the post-mortem marker levels. Post-mortem blood should be sampled as soon as possible, as increased post-mortem intervals may heavily change marker levels in-situ in individual cases, whereas the markers are mostly unaffected by laboratory conditions.

Authors: Lina Woydt, Michael Bernhard, Holger Kirsten, Ralph Burkhardt, Niels Hammer, André Gries, Jan Dreßler, Benjamin Ondruschka

Date Published: 1st Dec 2018

Publication Type: Journal article

Parameters of pulse wave velocity: determinants and reference values assessed in the population-based study LIFE-Adult
Genetical Statistics and Systems Biology

Abstract (Expand)

AIMS AND BACKGROUND Parameters of arterial stiffness such as pulse wave velocity (PWV) were recently proposed as independent risk factors of cardiovascular events. We analyse three PWV parameters in …n the large population-based study LIFE-Adult to identify risk factors, normal and reference values. METHODS AND RESULTS Brachial-ankle (ba), brachial-femoral (bf) and carotid-femoral (cf) PWV assessment was performed using Vicorder device. 8509 participants aged 19-80 were analysed. PWV parameters were moderately correlated (r(ba/bf) = 0.6, r(ba/cf) = 0.46, r(bf/cf) = 0.59). Age and blood pressure are the dominant determinants of PWV parameters explaining \textgreater 18% of variability. Sex was only relevant for bfPWV and cfPWV. All further analysed cardiovascular and other risk factors are of minor importance. We provide age-dependent percentiles for the population (reference values) and for the subgroup of normotonic individuals. All percentiles show a strong increase with age. The difference between normotonic and all individuals is small for younger age groups but increases up to 1 m/s for elderly subjects. CONCLUSION Our study confirms and further underpins the strong impact of age and blood pressure on arterial stiffness and the relatively weak contribution of other factors, supporting an independent role of arterial stiffness in cardiovascular disease development. Age-dependent reference and normal values were provided on the basis of the so far largest study sample facilitating the implementation of PWV assessment in clinical practice. Due to better compliance, handling and stronger association with age and blood pressure, baPWV could serve as an alternative to cfPWV. Follow-up data are required to estimate the clinical significance of specified PWV cut-offs.

Authors: Daniel Baier, Andrej Teren, Kerstin Wirkner, Markus Loeffler, Markus Scholz

Date Published: 1st Nov 2018

Publication Type: Journal article

Measurement of cerebral biomarkers proving traumatic brain injuries in post-mortem body fluids
Genetical Statistics and Systems Biology

Abstract (Expand)

Until now, it is impossible to identify a fatal traumatic brain injury (TBI) before post-mortem radiological investigations or an autopsy take place. It would be preferable to have an additional … diagnostic tool like post-mortem biochemistry to get greater insight into the pathological pathways and survival times after sustaining TBI. Cerebrospinal fluid (CSF) and serum samples of 84 autopsy cases were collected from forensic autopsies with post-mortem intervals (PMI) of up to 148 h. The cases were categorized into a fatal TBI case group (n=42) and non-TBI controls (n=42). The values of glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF) and neutrophil gelatinase-associated lipocalin (NGAL) were analyzed by means of quantitative chemiluminescent multiplex immunoassays. The main results indicate that the usage of liquid samples with good macroscopic quality is more relevant for meaningful biomarker analyses than the length of the PMI. All three proteins were shown to differentiate TBI fatalities from the controls in CSF. In serum, only GFAP could be shown to be able to identify TBI cases. This study is the first approach to measure the three proteins together in CSF and serum in autopsy cases. Determined threshold values may differentiate between fatal TBI and control cases. The presented results emphasize the possible use of post-mortem biochemistry as a supplemental tool in everyday forensic routine.

Authors: Benjamin Ondruschka, Monique Sieber, Holger Kirsten, Heike Franke, Jan Dressler

Date Published: 1st Sep 2018

Publication Type: Journal article

Prognostic and Pathogenic Role of Angiopoietin-1 and -2 in Pneumonia
Genetical Statistics and Systems Biology

Abstract (Expand)

RATIONALE During pneumonia, pathogen-host interaction evokes inflammation and lung barrier dysfunction. Tie2-activation by Angiopoietin-1 reduces, while Tie2-blockade by Angiopoietin-2 increases …s inflammation and permeability during sepsis. The role of Angiopoietin-1/-2 in pneumonia remains unidentified. OBJECTIVES To investigate the prognostic and pathogenetic impact of Angiopoietins in regulating pulmonary vascular barrier function and inflammation in bacterial pneumonia. METHODS Serum Angiopoietin levels were quantified in pneumonia patients of two independent cohorts (n=148, n=395). Human post mortem lung tissue, pneumolysin- or Angiopoietin-2-stimulated endothelial cells, isolated perfused and ventilated mouse lungs, and mice with pneumococcal pneumonia were investigated. MEASUREMENTS AND MAIN RESULTS In pneumonia patients, decreased serum Angiopoietin-1 and increased Angiopoietin-2 levels were observed as compared to healthy subjects. Higher Angiopoietin-2 serum levels were found in community-acquired pneumonia patients who died within 28 days after diagnosis compared to survivors. ROC analysis revealed improved prognostic accuracy of CURB-65 for 28-day survival, intensive care treatment and length of hospital stay if combined with Angiopoietin-2 serum levels. In vitro, pneumolysin enhanced endothelial Angiopoietin-2 release, Angiopoietin-2 increased endothelial permeability, and Angiopoietin-1 reduced pneumolysin-evoked endothelial permeability. Ventilated and perfused lungs of mice with Angiopoietin-2-knockdown showed reduced permeability upon pneumolysin stimulation. Increased pulmonary Angiopoietin-2 and reduced Angiopoietin-1 mRNA expression were observed in S. pneumoniae infected mice. Finally, Angiopoietin-1 therapy reduced inflammation and permeability in murine pneumonia. CONCLUSIONS These data suggest a central role of Angiopoietin-1/-2 in pneumonia-evoked inflammation and permeability. Increased Angiopoietin-2 serum levels predicted mortality and length of hospital stay, and Angiopoietin-1 may provide a therapeutic target for severe pneumonia.

Authors: Birgitt Gutbier, Anne-Kathrin Neuhauß, Katrin Reppe, Carolin Ehrler, Ansgar Santel, Jörg Kaufmann, Markus Scholz, Norbert Weissmann, Lars Morawietz, Timothy J. Mitchell, Stefano Aliberti, Stefan Hippenstiel, Norbert Suttorp, Martin Witzenrath

Date Published: 15th Jul 2018

Publication Type: Journal article

Common variants in the CLDN2-MORC4 and PRSS1-PRSS2 loci confer susceptibility to acute pancreatitis
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND/OBJECTIVES Acute pancreatitis (AP) is one of the most common gastrointestinal disorders often requiring hospitalization. Frequent aetiologies are gallstones and alcohol abuse. In contrast …t to chronic pancreatitis (CP) few robust genetic associations have been described. Here we analysed whether common variants in the CLDN2-MORC4 and the PRSS1-PRSS2 locus that increase recurrent AP and CP risk associate with AP. METHODS We screened 1462 AP patients and 3999 controls with melting curve analysis for SNPs rs10273639 (PRSS1-PRSS2), rs7057398 (RIPPLY), and rs12688220 (MORC4). Calculations were performed for the overall group, aetiology, and gender sub-groups. To examine genotype-phenotype relationships we performed several meta-analyses. RESULTS Meta-analyses of all AP patients depicted significant (p-value \textless 0.05) associations for rs10273639 (odds ratio (OR) 0.88, 95% confidence interval (CI) 0.81-0.97, p-value 0.01), rs7057398 (OR 1.27, 95% CI 1.07-1.5, p-value 0.005), and rs12688220 (OR 1.32, 95% CI 1.12-1.56, p-value 0.001). For the different aetiology groups a significant association was shown for rs10273639 (OR 0.76, 95% CI 0.63-0.92, p-value 0.005), rs7057398 (OR 1.43, 95% CI 1.07-1.92, p-value 0.02), and rs12688220 (OR 1.44, 95% CI 1.07-1.93, p-value 0.02) in the alcoholic sub-group only. CONCLUSIONS The association of CP risk variants with different AP aetiologies, which is strongest in the alcoholic AP group, might implicate common pathomechanisms most likely between alcoholic AP and CP.

Authors: Frank Ulrich Weiss, Nico Hesselbarth, Andrea Párniczky, Dora Mosztbacher, Felix Lämmerhirt, Claudia Ruffert, Peter Kovacs, Sebastian Beer, Katharina Seltsam, Heidi Griesmann, Richard Böhme, Tom Kaune, Marcus Hollenbach, Hans-Ulrich Schulz, Peter Simon, Julia Mayerle, Markus M. Lerch, Giulia Martina Cavestro, Raffaella Alessia Zuppardo, Milena Di Leo, Pier Alberto Testoni, Ewa Malecka-Panas, Anita Gasirowska, Stanislaw Głuszek, Peter Bugert, Andrea Szentesi, Joachim Mössner, Heiko Witt, Patrick Michl, Peter Hégyi, Markus Scholz, Jonas Rosendahl

Date Published: 1st Jul 2018

Publication Type: Journal article

Genetic Regulation of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Plasma Levels and Its Impact on Atherosclerotic Vascular Disease Phenotypes
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND Inhibition of PCSK9 (proprotein convertase subtilisin/kexin type 9) is a novel strategy to treat hypercholesterolemia and reduce cardiovascular events. However, the potential role of circulating …g plasma PCSK9 concentrations as a diagnostic and predictive biomarker remains uncertain as of now. Here, we aimed to identify genetic variants associated with plasma PCSK9 and investigate possible causal effects on atherosclerotic vascular disease phenotypes. METHODS We performed the first genome-wide association study of plasma PCSK9 levels in a cohort of suspected and confirmed coronary artery disease (LIFE-Heart; n=3290). RESULTS Several independent variants at the PCSK9 gene locus were associated with circulating PCSK9 levels at genome-wide significance (lead SNP rs11591147, PCSK9-R46L; P=1.94\times10-17). We discovered 4 independent PCSK9 SNPs explaining 4.4% of the variance of plasma PCSK9. In addition, we identified a genome-wide significant locus at chromosome 7p22.1 (rs6957201; P=7.01\times10-9) and 7 suggestive hits (P\textless1\times10-6). Using MR (Mendelian Randomization), we detected significant causal effects of circulating PCSK9 on coronary artery disease status and severity, carotid plaques, and intima-media thickness. CONCLUSIONS Variants at the PCSK9 gene locus seem to be the major genetic determinants of plasma PCSK9 levels with 4 independent variants at the PCSK9 gene locus expressing allelic heterogeneity. The detected MR estimates support the hypothesis of a causal effect of PCSK9 on coronary artery disease and other vascular phenotypes. Other observed genetic associations for PCSK9 require validation in independent cohorts. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00497887.

Authors: Janne Pott, Valentin Schlegel, Andrej Teren, Katrin Horn, Holger Kirsten, Christina Bluecher, Juergen Kratzsch, Markus Loeffler, Joachim Thiery, Ralph Burkhardt, Markus Scholz

Date Published: 1st May 2018

Publication Type: Journal article

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