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Modeling of age-dependent amyloid accumulation and γ-secretase inhibition of soluble and insoluble Aβ in a transgenic mouse model of amyloid deposition
According to the “amyloid hypothesis,” accumulation of amyloid beta (Aβ) peptides in the brain is linked to the development of Alzheimer's disease. The aims of this investigation were to develop aExpand
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Translational pharmacokinetic-pharmacodynamic modeling of QTc effects in dog and human.
INTRODUCTION Preclinical assessment of the heart rate corrected QT interval (QTc) is an important component of the cardiovascular safety evaluation in drug discovery. Here we aimed to quantify theExpand
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Has inhibition of Aβ production adequately been tested as therapeutic approach in mild AD? A model-based meta-analysis of γ-secretase inhibitor data
PurposeTo date, γ-secretase inhibition is the most frequently studied mechanism of reducing Aβ in clinical trials with as yet no therapeutic success for AD patients, as measured by the slowing downExpand
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Application of data mining and visualization techniques for the prediction of drug-induced nausea in man.
The therapeutic value of many drugs can be limited by gastrointestinal (GI) adverse effects such as nausea and vomiting. Nausea is a subjective human sensation, hence little is known aboutExpand
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Effects of isopropanol on collagen fibrils in new parchment
BackgroundIsopropanol is widely used by conservators to relax the creases and folds of parchment artefacts. At present, little is known of the possible side effects of the chemical on parchments mainExpand
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Predicting QRS and PR interval prolongations in humans using nonclinical data
Risk of cardiac conduction slowing (QRS/PR prolongations) is assessed prior to clinical trials using in vitro and in vivo studies. Understanding the quantitative translation of these studies to theExpand
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Parameter Identifiability of Fundamental Pharmacodynamic Models
We analyzed the structural identifiability of 16 commonly applied pharmacodynamic model structures was analyzed analytically, using the input-output approach. Expand
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PKPD modelling of PR and QRS intervals in conscious dogs using standard safety pharmacology data.
INTRODUCTION Pharmacokinetic-pharmacodynamic (PKPD) modelling can improve safety assessment, but few PKPD models describing drug-induced QRS and PR prolongations have been published. ThisExpand
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Comparison of pharmacokinetics and the exposure–response relationship of dapagliflozin between adolescent/young adult and adult patients with type 1 diabetes mellitus
To quantitatively compare pharmacokinetics (PK) and the exposure–response (ER) relationship of the sodium‐glucose cotransporter‐2 inhibitor, dapagliflozin, between adolescents/young adults and adultsExpand
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Exploring the insulin secretory properties of the PGD2-GPR44/DP2 axis in vitro and in a randomized phase-1 trial of type 2 diabetes patients
Aims/Hypothesis GPR44 (DP2, PTGDR2, CRTh2) is the receptor for the pro-inflammatory mediator prostaglandin D2 (PGD2) and it is enriched in human islets. In rodent islets, PGD2 is produced in responseExpand
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