Metabolomic Profiling in Patients with Different Hemodynamic Subtypes of Severe Aortic Valve Stenosis.

Severe aortic stenosis (AS) is a common pathological condition in an ageing population imposing significant morbidity and mortality. Based on distinct hemodynamic features, i.e.

Small Molecule BRD4 Inhibitors Apabetalone and JQ1 Rescues Endothelial Cells Dysfunction, Protects Monolayer Integrity and Reduces Midkine Expression.

NF-κB signaling is a key regulator of inflammation and atherosclerosis. NF-κB cooperates with bromodomain-containing protein 4 (BRD4), a transcriptional and epigenetic regulator, in endothelial inflammation. This study aimed to investigate whether BRD4 inhibition would prevent the proinflammatory response towards TNF-α in endothelial cells.

Biomarker profiles in heart failure with preserved vs. reduced ejection fraction: results from the DIAST-CHF study.

Aims: Chronic heart failure (HF) is a common disease and one of the leading causes of death worldwide. Heart failure with preserved ejection fraction (HFpEF) and with reduced ejection fraction (HFrEF) are different diseases with distinct as well as comparable pathophysiologies and diverse responses to therapeutic agents. We aimed to identify possible pathobiochemical signalling pathways and biomarkers in HFpEF and HFrEF by using a broad proteomic approach.

Comparison of a novel automated DiaSys procalcitonin immunoassay with four different BRAHMS-partnered immunoassays.

Objectives: Procalcitonin (PCT) is an important biomarker of sepsis and respiratory infections. Various automated immunoassays for measuring PCT in patient plasma are available in medical laboratories. However, due to a lack of international reference material for PCT, the assays are not always comparable.

Ultrasound-Induced Release of Nimodipine from Drug-Loaded Block Copolymer Micelles: In Vivo Analysis.

Nimodipine prevents cerebral vasospasm and improves functional outcome after aneurysmal subarachnoid hemorrhage (aSAH). The beneficial effect is limited by low oral bioavailability of nimodipine, which resulted in an increasing use of nanocarriers with sustained intrathecal drug release in order to overcome this limitation. However, this approach facilitates only a continuous and not an on-demand nimodipine release during the peak time of vasospasm development.

How family history of premature myocardial infarction affects patients at cardiovascular risk.

Objective: Family history of premature myocardial infarction (FH-MI) increases the risk for coronary heart disease (CHD). Research has shown that this effect cannot be accounted for by increased genetic vulnerability alone. We tested the hypothesis that FH-MI is associated with psychological distress, which is known to increase CHD risk, and that this effect is sustained over years and mediated by personality traits and coping strategies.

NT-proBNP as a marker for atrial fibrillation and heart failure in four observational outpatient trials.

Aims: Heart failure (HF) and atrial fibrillation (AF) frequently coexist and are both associated with increased levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP). It is known that AF impairs the diagnostic accuracy of NT-proBNP for HF. The aim of the present study was to compare the diagnostic and predictive accuracy of NT-proBNP for HF and AF in stable outpatients with cardiovascular risk factors.

Plasma Biomarker Profiling in Heart Failure Patients with Preserved Ejection Fraction before and after Spironolactone Treatment: Results from the Aldo-DHF Trial.

The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is poorly understood and therapeutic strategies are lacking. This study aimed to identify plasma proteins with pathophysiological relevance in HFpEF and with respect to spironolactone-induced effects. We assessed 92 biomarkers in plasma samples from 386 HFpEF patients-belonging to the Aldo-DHF trial-before (baseline, BL) and after one-year treatment (follow up, FU) with spironolactone (verum) or a placebo.

Inconsistent Findings of Cardiac Troponin T and I in Clinical Routine Diagnostics: Factors of Influence.

Cardiac troponins are crucial for the diagnosis of acute myocardial infarction. Despite known differences in their diagnostic implication, there are no recommendations for only one of the two troponins, cardiac troponin I (cTnI) and troponin T (cTnT) so far. In an everyday routine diagnostic, cTnT (Roche) as well as cTnI (Abbott) were measured in 5667 samples from 3264 patient cases.

The diagnostic and prognostic value of galectin-3 in patients at risk for heart failure with preserved ejection fraction: results from the DIAST-CHF study.

Aims: Galectin-3 (Gal-3) predicts long-term outcome among patients with heart failure (HF) with preserved ejection fraction (HFpEF). The ability of Gal-3 to diagnose and predict incident HFpEF in a cohort at risk for HFpEF is of particular interest. We aimed to determine the association between Gal-3 and clinical manifestations of HFpEF, the relationship between Gal-3 and all-cause mortality, or the composite of cardiovascular hospitalization and death.

Higher galectin-3 levels are independently associated with lower anxiety in patients with risk factors for heart failure.

Background: Galectin-3 promotes the proliferation of neural progenitor cells and is engaged in cell-cell adhesion, cell-matrix interactions, and macrophage activation. In addition, in patients with heart failure this carbohydrate-binding protein is a known prognostic marker for cardiovascular mortality. However, its association with psychological variables has not been investigated so far.

Outcome assessment using estimation of left ventricular filling pressure in asymptomatic patients at risk for heart failure with preserved ejection fraction.

Aims: High prevalence and lack of pharmacological treatment are making heart failure with preserved ejection fraction (HFpEF) a growing public health problem. No algorithm for the screening of asymptomatic patients with risk for HFpEF exists to date. We assessed whether HFA/ESC 2007 diagnostic criteria for HFpEF are helpful to investigate the cardiovascular outcome in asymptomatic patients.

Brain Natriuretic Peptide and Discovery of Atrial Fibrillation After Stroke: A Subanalysis of the Find-AF Trial.

Background and Purpose- Diagnosing paroxysmal atrial fibrillation (pAF) can be challenging after acute ischemic stroke. Enhanced and prolonged Holter-ECG monitoring (EPM) improves the detection rate but is not feasible for all patients. We hypothesized that brain natriuretic peptide (BNP) may help to identify patients with stroke at high risk for pAF to select patients for EPM more effectively.

Longitudinal relationship between B-type natriuretic peptide and anxiety in coronary heart disease patients with depression.

Objective: Patients with coronary heart disease (CHD) suffer from physical limitations, but also from psychological distress. Natriuretic peptides may be involved in the neurobiological processes that modulate psychological adaptation, as they are increased in heart disease and seem to have an anxiolytic-like function. Longitudinal data on this association are scarce.

Assessing the role of extracellular signal-regulated kinases 1 and 2 in volume overload-induced cardiac remodelling.

Aims: Volume overload (VO) and pressure overload (PO) induce differential cardiac remodelling responses including distinct signalling pathways. Extracellular signal-regulated kinases 1 and 2 (ERK1/2), key signalling components in the mitogen-activated protein kinase (MAPK) pathways, modulate cardiac remodelling during pressure overload (PO). This study aimed to assess their role in VO-induced cardiac remodelling as this was unknown.

Higher plasma levels of CT-proAVP are linked to less anxiety in men but not women with cardiovascular risk factors: Results from the observational Diast-CHF study.

Aim: Using data from the multicenter, observational Diast-CHF (Diagnostic Trial on Prevalence and Clinical Course of Diastolic Dysfunction and Heart Failure) study, this post-hoc analysis aimed at assessing the association between serum concentrations of C-terminal pro-arginine vasopressin (CT-proAVP) and anxiety in patients with cardiovascular risk factors.

Background: Animal studies have demonstrated that centrally released AVP is involved in the development of anxiety-like behaviors, however, it is unknown whether, also in humans, CT-proAVP used as a proxy for the co-secreted AVP is associated with self-reported anxiety.

Methods: In 1463 study participants with cardiovascular risk factors (mean age 66.

Macro-CK type 2 in metastatic prostate cancer.

The isoenzyme creatine kinase muscle/brain (CK-MB) still plays an important role for the differential diagnosis of CK elevations and the clarification of their origin from heart or skeletal muscle. Therefore, it is necessary to know the diagnostic pitfalls in interpreting CK-MB results. We demonstrate a case of macro-CK type 2 in a 75-year-old patient with metastatic castration-resistant prostate cancer and its identification by isoenzyme electrophoresis, which can be typical for cancer diseases.

Associations of NT-proBNP and parameters of mental health in depressed coronary artery disease patients.

Natriuretic peptides (NP) are involved in the regulation of blood pressure and blood volume, and are elevated in patients with coronary artery disease (CAD). They are used as markers for illness severity, but their role in mental health is not well understood. Recently, A-type NP (ANP) has been associated with reduced anxiety in studies on cardiac patients; however, this study is the first to assess this effect for B-type NP (BNP) and for further dimensions of well-being and mental health.

Systematic forensic toxicological analysis by liquid-chromatography-quadrupole-time-of-flight mass spectrometry in serum and comparison to gas chromatography-mass spectrometry.

Comprehensive screening procedures for psychoactive agents in body fluids are an essential task in clinical and forensic toxicology. With the continuous emergence and adaption of new psychoactive substances (NPS) keeping a screening method up to date is challenging. To meet these demands, hyphenated high-resolution mass spectrometry has gained interest as extensive and expandable screening approach.

MPA Modulates Tight Junctions' Permeability via Midkine/PI3K Pathway in Caco-2 Cells: A Possible Mechanism of Leak-Flux Diarrhea in Organ Transplanted Patients.

Mycophenolic acid (MPA) is prescribed to prevent allograft rejection in organ transplanted patients. However, its use is sporadically linked to leak flux diarrhea and other gastrointestinal (GI) disturbances in around 75% of patients through yet unknown mechanisms. Recently, we identified Midkine as a modulator of tight junctions (TJs) permeability in MPA treated Caco-2 monolayer.

Active and Repressive Chromatin-Associated Proteome after MPA Treatment and the Role of Midkine in Epithelial Monolayer Permeability.

Unlabelled: Mycophenolic acid (MPA) is prescribed to maintain allografts in organ-transplanted patients. However, gastrointestinal (GI) complications, particularly diarrhea, are frequently observed as a side effect following MPA therapy. We recently reported that MPA altered the tight junction (TJ)-mediated barrier function in a Caco-2 cell monolayer model system.

Immunosuppressant MPA Modulates Tight Junction through Epigenetic Activation of MLCK/MLC-2 Pathway via p38MAPK.

Background: Mycophenolic acid (MPA) is an important immunosuppressive drug (ISD) prescribed to prevent graft rejection in the organ transplanted patients, however, its use is also associated with adverse side effects like sporadic gastrointestinal (GI) disturbances. Recently, we reported the MPA induced tight junctions (TJs) deregulation which involves MLCK/MLC-2 pathway. Here, we investigated the global histone acetylation as well as gene-specific chromatin signature of several genes associated with TJs regulation in Caco-2 cells after MPA treatment.

The brain as immunoprecipitator of serum autoantibodies against N-Methyl-D-aspartate receptor subunit NR1.

Autoantibodies (AB) against N-methyl-D-aspartate receptor subunit NR1 (NMDAR1) are highly seroprevalent in health and disease. Symptomatic relevance may arise upon compromised blood-brain barrier (BBB). However, it remained unknown whether circulating NMDAR1 AB appear in the cerebrospinal fluid (CSF).

Natriuretic peptides for the detection of paroxysmal atrial fibrillation.

Background And Purpose: Silent atrial fibrillation (AF) and tachycardia (AT) are considered precursors of ischaemic stroke. Therefore, detection of paroxysmal atrial rhythm disorders is highly relevant, but is clinically challenging. We aimed to evaluate the diagnostic value of natriuretic peptide levels in the detection of paroxysmal AT/AF in a pilot study.