Publications by authors named "Alice Krebs"

Hazard assessment, based on new approach methods (NAM), requires the use of batteries of assays, where individual tests may be contributed by different laboratories. A unified strategy for such collaborative testing is presented. It details all procedures required to allow test information to be usable for integrated hazard assessment, strategic project decisions and/or for regulatory purposes.

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Human cell-based neural organoids are increasingly being used for investigations of neurotoxicity, and to study the pathophysiology of neurodegenerative diseases. Here, we present a fast and robust method to generate 3D cultured human dopaminergic neurons (LUHMES) for toxicity testing and long-term culture. Moreover, a plating step was introduced to allow generation of neurite networks with defined 2D orientation and several mm length, while all cell bodies (somata) remained in a 3D, dome-like structure.

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In this manuscript, which appeared in ALTEX (2019), 36(4), 682- 699, doi:10.14573/altex.1909271 , the affiliation of Hennicke Kamp should be Experimental Toxicology and Ecology, BASF SE, Ludwigshafen, Germany.

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Many toxicological test methods, including assays of cell viability and function, require an evaluation of concentration-response data. This often involves curve fitting, and the resulting mathematical functions are then used to determine the concentration at which a certain deviation from the control value occurs (e.g.

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While there are many methods to quantify the synthesis, localization, and pool sizes of proteins and DNA during physiological responses and toxicological stress, only few approaches allow following the fate of carbohydrates. One of them is metabolic glycoengineering (MGE), which makes use of chemically modified sugars (CMS) that enter the cellular biosynthesis pathways leading to glycoproteins and glycolipids. The CMS can subsequently be coupled (via bio-orthogonal chemical reactions) to tags that are quantifiable by microscopic imaging.

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Only few cell-based test methods are described by Organisation for Economic Co-operation and Development (OECD) test guidelines or other regulatory references (e.g., the European Pharmacopoeia).

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In this manuscript, which appeared in ALTEX 35 , 268-271 ( doi: 10.14573/1803231 ), the Acknowledgements should read: This work was supported by BMBF and DFG (KoRS-CB) grants, and it has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 681002 (EU-ToxRisk).

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Many types of assays in cell biology, pharmacology and toxicology generate data in which a parameter is measured in a reference system (negative control) and then also under conditions of increasing stress or drug exposure. To make such data easily comparable, they are normalized, i.e.

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Many in vitro tests have been developed to screen for potential neurotoxicity. However, only few cell function-based tests have been used for comparative screening, and thus experience is scarce on how to confirm and evaluate screening hits. We addressed these questions for the neural crest cell migration test (cMINC).

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Halogen-free organophosphorus flame retardants are considered as replacements for the phased-out class of polybrominated diphenyl ethers (PBDEs). However, toxicological information on new flame retardants is still limited. Based on their excellent flame retardation potential, we have selected three novel 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) derivatives and assessed their toxicological profile using a battery of in vitro test systems in order to provide toxicological information before their large-scale production and use.

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The purpose of this study was to analyze comprehensively the heart using modern and sensitive myocardial techniques in order to determine if structural or functional cardiac alterations are present in adult Pompe disease. Twelve patients with adult Pompe disease and a control group of 187 healthy subjects of similar age and gender were included. Structural and functional cardiac characteristics were analyzed by conventional and 2D speckle-tracking echocardiography.

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The aim of this study was to test the hypothesis that in patients with Fabry disease, 2D speckle-tracking echocardiography (2DSTE) could detect functional myocardial alterations such as left ventricular (LV), right ventricular (RV), and left atrial (LA) dysfunction, even when conventional cardiac measurements are normal. In addition, we hypothesized that these global cardiac alterations could be linked to worse symptomatic status in these patients. Fifty patients with Fabry disease and a control group of 118 healthy subjects of similar age and gender were included.

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Because of the shortage of agalsidase-beta in 2009, many patients with Fabry disease were treated with lower doses or were switched to agalsidase-alfa. This observational study assessed end-organ damage and clinical symptoms during dose reduction or switch to agalsidase-alfa. A total of 105 adult patients with Fabry disease who had received agalsidase-beta (1.

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Cancer cells in poorly vascularized tumor regions need to adapt to an unfavorable metabolic microenvironment. As distance from supplying blood vessels increases, oxygen and nutrient concentrations decrease and cancer cells react by stopping cell cycle progression and becoming dormant. As cytostatic drugs mainly target proliferating cells, cancer cell dormancy is considered as a major resistance mechanism to this class of anti-cancer drugs.

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Aims: Mortality in chronic heart failure (CHF) patients with left bundle branch block (LBBB) is high. Cardiac resynchronization therapy (CRT) reduces symptoms and mortality in CHF patients with LBBB. Whether CRT promotes or prevents ventricular tachycardia (VT)/ventricular fibrillation (VF) remains controversial, however.

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Evidence-based treatment for heart failure (HF) comprises beta-blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone receptor antagonists (ARA). Diuretics (DR) are prescribed in acute and chronic HF, but their impact on survival and ventricular tachyarrhythmias (VT/VF) is unclear. The present observational study aims to examine the influence of DR and ARA on survival and appropriate cardioverter/defibrillator (ICD) treatment episodes in routine ICD patients.

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Aims: Data from previous defibrillator studies raised concern about right ventricular pacing (RVP) promoting heart failure progression and mortality in implantable cardioverter/defibrillator (ICD) patients. The present observational study re-examined the association of RVP, survival, and ventricular tachyarrhythmias/ventricular fibrillation (VT/VF) in routine ICD patients with restrictively programmed pacing.

Methods And Results: In 213 ICD patients [183 men, left ventricular ejection fraction (LVEF) 37 +/- 15%, follow-up 37 +/- 18 months, no advanced atrioventricular (AV) block], the RVP proportion, survival, and the time to a first appropriate VT/VF episode were assessed.

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Background: Most patients with symptomatic sinus node disease (SND) receive DDDR pacemakers (PM) in order to cover SND and atrioventricular (AV) block from the outset. But the concern about adverse effects of right ventricular pacing (RVP) is increasing. So far, data on the incidence of AV block in SND are based on clinical events.

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Background: Implantable cardioverter-defibrillators (ICD) implanted after an episode of ventricular tachyarrhythmia (VTA) or in patients at high risk of VTA lower the long-term mortality. Comparisons of the clinical outcomes of the two indications are scarce.

Methods: The study enrolled 360 consecutive ICD recipients.

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Background: Cardiac resynchronization therapy (CRT) reduces the left ventricular diameter (LVEDD) in heart failure (HF) patients with left bundle branch block (LBBB). The study compares structural and electrical remodeling in HF patients on CRT and matched HF controls without LBBB.

Methods: In 42 patients (64 +/- 9 years left ventricular ejection fraction [LVEF] 25 +/- 8%, 16 coronary artery disease, 26 nonischemic cardiomyopathy, 21 with LBBB and CRT indication vs 21 controls [matched for gender, age, LVEF, and underlying disease]) an unpaced electrocardiogram (ECG) and echocardiogram were recorded at baseline (bl) and after 20.

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Aims: The identification of responders to cardiac resynchronization therapy (CRT) in patients with left ventricular (LV) dysfunction and left bundle branch block (LBBB) remains difficult. We aimed to define the predictive value of conventional Doppler parameters.

Methods And Results: In 73 patients (65 +/- 9 years, 51 male, 36 ischaemic, 37 non-ischaemic cardiomyopathy, QRS 167 +/- 31 ms, LVEF 23 +/- 6%) with LBBB, a CRT device was implanted.

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Microcephalin (MCPH1) is a gene mutated in primary microcephaly, an autosomal recessive neurodevelopmental disorder in which there is a marked reduction in brain size. PCC syndrome is a recently described disorder of microcephaly, short stature, and misregulated chromosome condensation. Here, we report the finding that MCPH1 primary microcephaly and PCC syndrome are allelic disorders, both having mutations in the MCPH1 gene.

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