A5109864861- Nitric Oxide and Endothelin Effects
- Acute Kidney Injury Research
- Renin-Angiotensin System Studies
- Hormonal Regulation and Hypertension
- Chronic Kidney Disease and Diabetes
- NMR spectroscopy and applications
- Advanced NMR Techniques and Applications
- Eicosanoids and Hypertension Pharmacology
- Ion Transport and Channel Regulation
- Thyroid Disorders and Treatments
- Advanced MRI Techniques and Applications
- Chemical Synthesis and Analysis
- Dialysis and Renal Disease Management
- Advanced Neuroimaging Techniques and Applications
- Phosphodiesterase function and regulation
- Synthesis and Reactions of Organic Compounds
- Adenosine and Purinergic Signaling
- Fluorine in Organic Chemistry
- Electrolyte and hormonal disorders
- Growth Hormone and Insulin-like Growth Factors
- Advanced biosensing and bioanalysis techniques
- Polymer Nanocomposites and Properties
- Cardiac Ischemia and Reperfusion
- Advanced Glycation End Products research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
Hochschule Bonn-Rhein-Sieg
2024
Bayer (Germany)
2012-2022
Bayer (United States)
2012-2013
Target (Germany)
2010
Max Planck Institute for Polymer Research
2002-2003
Max Planck Society
2002-2003
Humboldt-Universität zu Berlin
1997
Technische Universität Dresden
1988
Technische Universität Braunschweig
1982-1983
Pharmacological blockade of the mineralocorticoid receptor (MR) ameliorates end-organ damage in chronic heart failure. However, clinical use available steroidal MR antagonists is restricted because concomitant hyperkalemia especially patients with diminished kidney function. We have recently identified a novel nonsteroidal antagonist, finerenone, which uniquely combines potency and selectivity toward MR. Here, we investigated tissue distribution cardiorenal protection finerenone comparison...
Lipophilic compounds of the culture suspension containing Rhodococcus erythropolis DSM43215 had surfactant properties when bacteria were cultivated with n -alkanes as sole carbon source. Thirteen main components from a dichloromethane-methanol extract R. cultures isolated and characterized to specify quantitatively their properties, e.g., minimum surface interfacial tensions critical micelle concentrations. The activity organic was dominated by α,α-trehalose-6,6′-dicorynomycolates which...
The first-in-class soluble guanylate cyclase (sGC) stimulator riociguat was recently introduced as a novel treatment option for pulmonary hypertension. Despite its outstanding pharmacological profile, application of in other cardiovascular indications is limited by short half-life, necessitating three times daily dosing regimen. In our efforts to further optimize the compound class, we have uncovered interesting structure-activity relationships and were able decrease oxidative metabolism...
Background The nitric oxide (NO)–soluble guanylate cyclase (sGC)–cyclic guanosine monophosphate (cGMP) signal-transduction pathway is impaired in many cardiovascular diseases, including pulmonary arterial hypertension (PAH). Riociguat (BAY 63–2521) a stimulator of sGC that works both synergy with and independently NO to increase levels cGMP. aims this study were investigate the role NO–sGC–cGMP signaling model severe PAH evaluate effects stimulation by riociguat PDE5 inhibition sildenafil on...
<i>Background:</i> Arteriosclerosis and cardiovascular disease are strongly associated with vascular calcification. Hyperphosphatemia is an essential risk factor for increased End-stage renal (ESRD) patients could serve as in vivo model accelerated This study focuses on the most likely protective effects of magnesium ion (Mg<sup>2+</sup>) phosphate-induced calcification ex vivo/in vitro. Furthermore, plasma Mg<sup>2+</sup> concentrations ESRD healthy...
A direct pharmacological stimulation of soluble guanylate cyclase (sGC) is an emerging therapeutic approach to the management various cardiovascular disorders associated with endothelial dysfunction. Novel sGC stimulators, including riociguat (BAY 63-2521), have a dual mode action: They sensitize endogenously produced nitric oxide (NO) and also directly stimulate independently NO. Little known about their effects on tissue remodeling degeneration survival in experimental malignant...
As the prevalence of diabetes rises, its complications such as diabetic nephropathy affect an increaseing number patients. Consequently, need for biomarkers in rodent models which reflect stage and course is high. This article focuses on Heart-type fatty acid binding protein (H-FABP), osteopontin (OPN), nephrin, Neutrophil gelatinase-associated lipocalin (NGAL) urine, kidney injury molecule (KIM)-1, clusterin, tissue inhibitior metalloproteinases (TIMP) 1 plasma uni-nephrectomized rats with...
Epidemiological studies exploring the connection between hypertension and cancer demonstrate a higher incidence, especially of kidney cancer, mortality in hypertensive patients. Hormones elevated hypertension, i.e., aldosterone angiotensin II, which exert genotoxic effects vitro, could contribute to carcinogenesis hypertension. The present study was conducted investigate possible DNA-damaging effect receptor activation vivo. Crl:CD (Sprague-Dawley) rats were treated for 6 wk with...
Heart failure with preserved ejection fraction (HFpEF) can arise from cardiac and vascular remodeling processes following long-lasting hypertension. Efficacy of common HF therapeutics is unsatisfactory in HFpEF. Evidence suggests that stimulators the nitric oxide–sensitive soluble guanylyl cyclase (NOsGC) could be use here. We aimed to characterize complex cardiovascular effects NOsGC stimulation using NO-independent stimulator BAY 41-8543 a double-transgenic rat (dTGR) model show...
The family of angiotensin peptides has been steadily growing in recent years. Most are fragments II (Ang II) with different affinities to the known receptors. Here, we describe a novel endogenous Ang II-like octapeptide plasma from healthy humans and patients end-stage renal failure, which acts as stronger agonist at Mas receptors than 1–7. Chromatographic purification structural analysis by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) revealed an...
The prevalence of diabetes mellitus and its complications, such as diabetic nephropathy (DN), is rising worldwide prevention treatment are therefore becoming increasingly important. Therapy DN particularly important for patients who do not adequately respond to angiotensin receptor blocker (ARB) treatment. Novel approaches include the stimulation soluble guanylate cyclase (sGC) it reported have beneficial effects on cardiac renal damage. We aimed investigate sGC stimulator riociguat ARB...
Stimulation of the nitric oxide (NO)--soluble guanylate (sGC)--protein kinase G (PKG) pathway confers protection against acute ischaemia/reperfusion injury, but more chronic effects in reducing post-myocardial infarction (MI) heart failure are less defined. The aim this study was to not only determine whether sGC stimulator riociguat reduces infarct size also it protects development post-MI failure.Mice were subjected 30 min ischaemia via ligation left main coronary artery induce MI and...
Vitamin-D-binding protein (VDBP) is a low molecular weight that filtered through the glomerulus as 25-(OH) vitamin D 3/VDBP complex. In normal kidney VDBP reabsorbed and catabolized by proximal tubule epithelial cells reducing urinary excretion to trace amounts. Acute tubular injury expected result in loss. The purpose of our study was explore potential role biomarker an acute renal damage.We included 314 patients with diabetes mellitus or mild impairment undergoing coronary angiography...
We have identified five cDNA clones that encode nicotinic acetylcholine receptor (nAChR) subunits expressed in the nervous system of locust Locusta migratoria. Four are ligand-binding α subunits, and other is a structural β subunit. The existence at least one more nAChR gene, probably encoding subunit, indicated.Based on Northern analysis situ hybridization, subunit genes expressed. locα1, locα3, andlocβ1 most abundant similar areas head ganglia retina adult locust. Because Locα3 binds...
To assess (a) plasma osteopontin (pOPN) in a cohort of chronic kidney disease (CKD) patients; (b) the relationship between pOPN and aortic calcification stiffness, (c) association overall cardiovascular mortality risk.pOPN, abdominal score pulse wave velocity (PWV) were determined 94 CKD patients (68 ± 13 years; 60% males; 31% at stages 2-3, 4-5, 38% stage 5D), prospectively followed for mortality.pOPN was higher than controls. Interleukin (IL)-6 (r(2) = 0.086; p 0.004), CRP 0.046; 0.038),...
Abstract Chronic kidney diseaQueryse (CKD) is associated with oxidative stress which can interrupt the nitric oxide (NO)/soluble guanylyl cyclase (sGC) signaling and decrease cyclic guanosine monophosphate (cGMP) production. Low cGMP concentrations cause damage progression of CKD. The novel sGC activator runcaciguat targets oxidized heme-free form sGC, restoring production under stress. purpose this study to investigate if could provide an effective treatment for Runcaciguat was used not...
Magic angle spinning at sufficiently high rates dramatically changes the sample temperature. A method is described for calibrating a probe head thermal effects encountered during magnic experiments. Using Sm2Sn2O7 as chemical shift thermometer, overlapping of 'external' heating or cooling by bearing gas and 'internal' friction on actual temperature were studied. The empirical expression Ts=0.12νr2+(3.47-0.013Tb)νr+0.80Tb+58.6 describes influence Tb (K) rate νr (kHz) Ts (K). © 1997 John Wiley...
The nitric oxide (NO)/soluble guanylate cyclase (sGC)/cyclic guanosine monophasphate (cGMP)-signalling pathway is impaired under oxidative stress conditions due to oxidation and subsequent loss of the prosthetic sGC heme group as observed in particular chronic renal failure. Thus, pool free increased pathological conditions. activators such cinaciguat selectively activate form target disease associated enzyme. In this study, a therapeutic effect long-term activation by activator was...
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Monitoring the kinetics of hydrolysis and condensation γ-glycidoxypropyltrimethoxy-silane (γ-GPS) was carried out by NMR spectroscopy (29Si–, 13C–, 1H–). The course these reactions followed in 2 wt% aqueous dilution conditions (26% D2O/74% H2O), pH 5.4, temperatures 26, 50, 70°C. At ambient temperature, proceed at very different time scales: a few hours for versus several weeks condensation. Distortionless Enhancement Polarization Transfer (DEPT) sequences 29Si– 13C–NMR were optimized...