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3. Circulating pyridoxal 5′-phosphate in serum and whole blood: implications for assessment of vitamin B6 status

Author

Obeid Rima, Möller Christoph, and Geisel Jürgen

Subjects
cystathionine, deficiency, homocysteine, pyridoxal 5′-phosphate, thiamine pyrophosphate, vitamin b6, Medical technology, R855-855.5
Abstract

Concentrations of pyridoxal 5′-phosphate (PLP) in serum and whole blood are routinely measured. The suitability of these markers in capturing vitamin B6 insufficiency is not well studied.

Published
2023
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4. TNF-related apoptosis-inducing ligand, interferon gamma-induced protein 10, and C-reactive protein in predicting the progression of SARS-CoV-2 infection: a prospective cohort study

Author

Tegethoff, Sina A., Danziger, Guy, Kühn, Dennis, Kimmer, Charlotte, Adams, Thomas, Heintz, Lena, Metz, Carlos, Reifenrath, Katharina, Angresius, Rebecca, Mang, Sebastian, Rixecker, Torben, Becker, André, Geisel, Jürgen, Jentgen, Christophe, Seiler, Frederik, Reichert, Matthias C., Fröhlich, Franziska, Meyer, Sascha, Rissland, Jürgen, Ewen, Sebastian, Wagenpfeil, Gudrun, Last, Katharina, Smola, Sigrun, Bals, Robert, Lammert, Frank, Becker, Sören L., Krawczyk, Marcin, Lepper, Philipp M., and Papan, Cihan

Published
2022
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7. German federal-state-wide seroprevalence study of 1st SARS-CoV-2 pandemic wave shows importance of long-term antibody test performance

Author

Lohse, Stefan, Sternjakob-Marthaler, Anna, Lagemann, Paul, Schöpe, Jakob, Rissland, Jürgen, Seiwert, Nastasja, Pfuhl, Thorsten, Müllendorff, Alana, Kiefer, Laurent S., Vogelgesang, Markus, Vella, Luca, Denk, Katharina, Vicari, Julia, Zwick, Anabel, Lang, Isabelle, Weber, Gero, Geisel, Jürgen, Rech, Jörg, Schnabel, Bernd, Hauptmann, Gunter, Holleczek, Bernd, Scheiblauer, Heinrich, Wagenpfeil, Stefan, and Smola, Sigrun

Published
2022
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11. Neutrophil extracellular trap biomarkers in aneurysmal subarachnoid hemorrhage: early decline of DNase 1 activity associated with delayed cerebral ischemia.

Author

Hendrix, Philipp, Witsch, Jens, Spalart, Valérie, Schneider, Hauke, Oertel, Joachim, Geisel, Jürgen, Martinod, Kimberly, and Hemmer, Sina

Subjects
CEREBRAL ischemia, SUBARACHNOID hemorrhage, CEREBRAL infarction, NEUTROPHILS, CELL-free DNA
Abstract

Introduction: High-mobility group box 1 (HMGB1) protein is a critical mediator of neutrophil extracellular trap (NET) formation (NETosis). Myeloperoxidase (MPO)- DNA complexes, a biomarker of NETs, and HMGB1 have been associated with delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Additional mechanistic NET-related biomarkers and their role in the neuroinflammatory cascade surrounding DCI remain to be explored. Methods: A post-hoc analysis of a prospective, blinded, single-center biomarker observational study was performed. De novo measurements of serum citrullinated histone H3-DNA complexes (H3Cit-DNA), peptidylarginine deiminase 4 (PAD4), cell-free DNA (cf-DNA), and DNase 1 activity were conducted on admission (D0) and day 4 (D4). Delayed cerebral infarction (DCI) was defined as new cerebral infarction on CT head not present on the post-treatment scan. Results: H3Cit-DNA, PAD4, cf-DNA, and DNase 1 activity were within quantifiable ranges in all serum samples analyzed at D0 and D4. Admission biomarker levels were not associated with DCI development. From D0 to D4, in both the DCI and the non-DCI groups, H3Cit-DNA levels significantly decreased, cf-DNA levels significantly increased, and PAD4 levels remained stable. In contrast, DNase 1 activity significantly decreased from D0 to D4 in the DCI group (p < 0.001) but not in the non-DCI group. Conclusion: This exploratory analysis demonstrated NET-related biomarkers such as H3Cit-DNA, PAD4, cf-DNA, and DNase 1 activity in all aSAH patients. A decline of systemic DNase 1 activity in the early phase might increase the risk of delayed cerebral ischemia. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Antibiotic therapeutic drug monitoring in intensive care patients treated with different modalities of extracorporeal membrane oxygenation (ECMO) and renal replacement therapy: a prospective, observational single-center study

Author

Kühn, Dennis, Metz, Carlos, Seiler, Frederik, Wehrfritz, Holger, Roth, Sophie, Alqudrah, Mohammad, Becker, André, Bracht, Hendrik, Wagenpfeil, Stefan, Hoffmann, Mathias, Bals, Robert, Hübner, Ulrich, Geisel, Jürgen, Lepper, Philipp M., and Becker, Sören L.

Published
2020
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21. ELOVL2‐methylation and renal and cardiovascular event in patients with chronic kidney disease.

Author

Obeid, Rima, Rickens, Patricia, Heine, Gunnar Henrik, Emrich, Insa E., Fliser, Danilo, Zawada, Adam M., Bodis, Marion, and Geisel, Jürgen

Subjects
CHRONIC kidney failure, CHRONICALLY ill, CARDIOVASCULAR diseases risk factors, PREMATURE aging (Medicine), DISEASE risk factors, KIDNEY diseases
Abstract

Background: Methylation of the Elongation Of Very Long Chain Fatty Acids‐Like 2 (ELOVL2) gene promoter may predict premature ageing and cardiovascular risk. Methods: We studied the cross‐sectional associations between blood ELOVL2‐methylation and cardiovascular risk factors in 350 patients with chronic kidney disease (CKD) stage G2–G4 aged between 22 and 90 years. In a follow‐up study for a mean of 3.9 years, we investigated the association between baseline ELOVL2‐methylation and renal or cardiovascular events including death. Results: ELOVL2‐methylation at seven CpG cites increased with age (the correlation coefficients between 0.67 and 0.87, p < 0.001). The ELOVL2‐CpGs methylation was lower in patients with CKD stage G2 versus those in stage G3a, G3b and G4, but the differences were explained by age. ELOVL2‐CpGs methylation showed no correlations with cardiovascular risk factors after adjusting for age. During the follow‐up, 64 patients showed deterioration in renal function or died and 77 showed cardiovascular events or died. The hazard ratio and 95% confidence intervals for renal or cardiovascular events according to baseline ELOVL2‐CpGs methylation were not significant after adjustment for covariates. Conclusions: ELOVL2‐hypermethylation showed a strong association with age, but was not independently associated with cardiovascular risk factors or with future renal or cardiovascular events in patients with CKD. ELOVL2 gene methylation is not likely to be itself a cause for ageing or illnesses, but it could be rather influenced by other upstream processes that deserve investigation. [ABSTRACT FROM AUTHOR]

Published
2023
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29. Abnormal High-Density Lipoprotein Induces Endothelial Dysfunction via Activation of Toll-like Receptor-2

Author

Speer, Thimoteus, Rohrer, Lucia, Blyszczuk, Przemyslaw, Shroff, Rukshana, Kuschnerus, Kira, Kränkel, Nicolle, Kania, Gabriela, Zewinger, Stephen, Akhmedov, Alexander, Shi, Yi, Martin, Tina, Perisa, Damir, Winnik, Stephan, Müller, Maja F., Sester, Urban, Wernicke, Gabriel, Jung, Andreas, Gutteck, Ursula, Eriksson, Urs, Geisel, Jürgen, Deanfield, John, von Eckardstein, Arnold, Lüscher, Thomas F., Fliser, Danilo, Bahlmann, Ferdinand H., and Landmesser, Ulf

Published
2013
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30. Die Assoziation von Myeloperoxidase-DNA-Komplexen und High Mobility Group Box 1 Protein mit verzögerter zerebraler Ischämie nach aneurysmatischer Subarachnoidalblutung

Author

Hendrix, Philipp, Witsch, Jens, Spalart, Valerie, Martinod, Kimberly, Schneider, Hauke, Oertel, Joachim, Geisel, Jürgen, and Hemmer, Sina

Subjects
ddc: 610, Medicine and health, chemical and pharmacologic phenomena, cardiovascular diseases
Abstract

Objective: High mobility group box 1 protein (HMGB1) acts as a key player in aseptic inflammation. Admission serum HMGB1 serves as an independent biomarker predictive of delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage (aSAH). Released by leucocytes and platelets, HMGB1 has been [for full text, please go to the a.m. URL]

Published
2022

37. The Erythrocyte Sedimentation Rate and Its Relation to Cell Shape and Rigidity of Red Blood Cells from Chorea-Acanthocytosis Patients in an Off-Label Treatment with Dasatinib

Author

Rabe, Antonia, Kihm, Alexander, Darras, Alexis, Peikert, Kevin, Simionato, Greta, Dasanna, Anil Kumar, Glaß, Hannes, Geisel, Jürgen, Quint, Stephan, Danek, Adrian, Wagner, Christian, Fedosov, Dmitry A., Hermann, Andreas, and Kaestner, Lars

Subjects
Adult, Male, Erythrocytes, microfluidics, therapeutic use [Dasatinib], 3D shapes, Blood Sedimentation, drug effects [Acanthocytes], cell rigidity, Microbiology, Article, ddc:570, therapeutic use [Protein Kinase Inhibitors], Humans, dasatinib, acanthocytes, Cell Shape, Protein Kinase Inhibitors, drug effects [Cell Shape], blood [Biomarkers], drug therapy [Neuroacanthocytosis], Off-Label Use, QR1-502, pathology [Acanthocytes], phase diagram, mesoscopic modeling, drug effects [Blood Sedimentation], drug effects [Erythrocytes], erythrocyte sedimentation rate, blood [Neuroacanthocytosis], Biomarkers, Neuroacanthocytosis, pathology [Neuroacanthocytosis]
Abstract

Background: Chorea-acanthocytosis (ChAc) is a rare hereditary neurodegenerative disease with deformed red blood cells (RBCs), so-called acanthocytes, as a typical marker of the disease. Erythrocyte sedimentation rate (ESR) was recently proposed as a diagnostic biomarker. To date, there is no treatment option for affected patients, but promising therapy candidates, such as dasatinib, a Lyn-kinase inhibitor, have been identified. Methods: RBCs of two ChAc patients during and after dasatinib treatment were characterized by the ESR, clinical hematology parameters and the 3D shape classification in stasis based on an artificial neural network. Furthermore, mathematical modeling was performed to understand the contribution of cell morphology and cell rigidity to the ESR. Microfluidic measurements were used to compare the RBC rigidity between ChAc patients and healthy controls. Results: The mechano-morphological characterization of RBCs from two ChAc patients in an off-label treatment with dasatinib revealed differences in the ESR and the acanthocyte count during and after the treatment period, which could not directly be related to each other. Clinical hematology parameters were in the normal range. Mathematical modeling indicated that RBC rigidity is more important for delayed ESR than cell shape. Microfluidic experiments confirmed a higher rigidity in the normocytes of ChAc patients compared to healthy controls. Conclusions: The results increase our understanding of the role of acanthocytes and their associated properties in the ESR, but the data are too sparse to answer the question of whether the ESR is a suitable biomarker for treatment success, whereas a correlation between hematological and neuronal phenotype is still subject to verification.

Published
2021
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38. Concentrations of Soluble Angiotensin Converting Enzyme 2 (sACE2) in Children and Adults with and without COVID-19.

Author

Wissing, Sarah Isabella, Obeid, Rima, Rädle-Hurst, Tanja, Rohrer, Tilman, Herr, Christian, Schöpe, Jakob, Geisel, Jürgen, Bals, Robert, and Abdul-Khaliq, Hashim

Subjects
ANGIOTENSIN converting enzyme, SARS-CoV-2, COVID-19, COVID-19 pandemic
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19) pandemic, leads to illness and death. Various risk factors for a severe course, such as higher age, male gender and pre-existing illnesses are known. However, pathophysiological risk factors are largely unclear. Notably, the mild course of disease in children is conspicuous. Angiotensin converting enzyme 2 (ACE2) serves as a receptor for SARS-CoV-2 and is a key enzyme in infection. Differences in the distribution of ACE2 can provide insights into different courses of COVID-19. Our aim was to elucidate the role of ACE2 as a pathophysiological risk factor by measuring soluble ACE2 (sACE2) via ELISA in blood samples (lithium-heparin-plasma or serum) of 367 individuals including children and adults with and without COVID-19. sACE2-levels were compared between the groups according to age and sex. In adults and children with COVID-19, sACE2-concentrations are significantly higher compared to healthy individuals. sACE2-levels increase with age and are lower in children compared to adults with COVID-19. Sex doesn't significantly influence sACE2-concentration. It remains unclear whether sACE2 concentrations increase because of the infection and what factors could influence this response. In conclusion, the increase of sACE2-concentration with age could indicate that ACE2 concentrations mirror increased COVID-19 severity. [ABSTRACT FROM AUTHOR]

Published
2022
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48. Monocyte heterogeneity in obesity and subclinical atherosclerosis

Author

Rogacev, Kyrill S., Ulrich, Christof, Blömer, Lutz, Hornof, Florian, Oster, Katrin, Ziegelin, Maren, Cremers, Bodo, Grenner, Yvonne, Geisel, Jürgen, Schlitt, Axel, Köhler, Hans, Fliser, Danilo, Girndt, Matthias, and Heine, Gunnar H.

Published
2010

50. 4-Pyridoxic Acid/Pyridoxine Ratio in Patients with Type 2 Diabetes is Related to Global Cardiovascular Risk Scores

Author

Obeid, Rima, Geisel, Jürgen, and Nix, Wilfred A.

Subjects
vitamin B6 catabolism, lcsh:R5-920, diabetes, vitamin deficiency, 4-pyridoxic acid, vascular risk, lcsh:Medicine (General), Article
Abstract

Background: Vascular diseases are multifactorial and several risk factors may have synergetic effect on the global vascular risk. Among patients with diabetes, we investigated whether vitamin B6 species differ according to global cardiovascular risk. Methods: The present observational study included 122 patients with type 2 diabetes (mean (SD) age = 69.9 (9.1) years; 50% men). Concentrations of vitamin B6 vitamers were measured. Classical blood biomarkers and risk factors were used to compute a multivariate risk score. Results: Plasma concentrations of 4-pyridoxic acid were higher in patients with high risk versus those with low risk scores (48.2 (63.7) vs. 31.9 (15.0) nmol/L; p = 0.031). Plasma pyridoxine was significantly lowered in patients at high risk (2.8 (28.4) vs. 38.1 (127.8) nmol/L; p = 0.003). PAr index (4-pyridoxic acid/pyridoxal + pyridoxal 5′-phosphate) (1.05 (0.07) vs. 0.84 (0.06); p = 0.017) and the ratio of 4-pyridoxic acid/pyridoxine (7.0 (4.8) vs. 3.9 (3.2); p < 0.001) were higher in patients at high risk. After adjustment for cystatin C and C-reactive protein, only pyridoxine and 4-pyridoxic acid/pyridoxine ratio remained significantly different according to vascular risk scores. 4-Pyridoxic acid/pyridoxine ratio was the best marker to discriminate between patients according to their risk scores—area under the curve (AUC) (95% confidence intervals (CI)) = 0.72 (0.62–0.81). 4-Pyridoxic acid/pyridoxine ratio was directly related to plasma levels of soluble vascular cell adhesion molecule 1. Conclusion: Vitamin B6 metabolism was shifted in patients with multiple vascular risk factors. The catabolism to 4-pyridoxic acid was enhanced, whereas the catabolism to pyridoxine was lowered. High 4-Pyridoxic acid/pyridoxine ratio is independently associated with global cardiovascular risk.

Published
2019

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