A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain.

The mammalian brain consists of millions to billions of cells that are organized into many cell types with specific spatial distribution patterns and structural and functional properties. Here we report a comprehensive and high-resolution transcriptomic and spatial cell-type atlas for the whole adult mouse brain. The cell-type atlas was created by combining a single-cell RNA-sequencing (scRNA-seq) dataset of around 7 million cells profiled (approximately 4.

A highly sensitive and selective UPLC-MS/MS assay for the determination of enarodustat (JTZ-951) in human plasma.

Enarodustat, a potent, orally bioavailable, selective inhibitor of hypoxia inducible factor-Prolyl hydroxylase (HIF-PH), has been approved recently in Japan for the treatment of anemia in patients with chronic kidney disease (CKD). To evaluate the pharmacokinetics of enarodustat, a bioanalytical assay in human plasma was needed for the quantitation of enarodustat for both healthy subjects and patients with CKD. The UPLC-MS/MS method for the quantitation of enarodustat was initially validated in a bioanalytical laboratory in Japan to support clinical studies conducted in Japan, and then was transferred and validated in a bioanalytical laboratory in United States to support clinical studies conducted here.

A sensitive LC-MS-MS assay for the determination of lapatinib in human plasma in subjects with end-stage renal disease receiving hemodialysis.

Most bioanalytical methods reported in literature for the quantitation of lapatinib in human plasma are either for lapatinib alone or lapatinib administered along with other tyrosine kinase inhibitors (TKIs) for therapeutic drug monitoring (TDM) in cancer patients. Recently there was a need for the quantitation of lapatinib in patients with end-stage renal disease (ESRD) receiving hemodialysis (HD). This special patient population normally receives many concomitant medications which have the potential to interfere with the quantitation of lapatinib.

Bioanalysis of ibrutinib and its active metabolite in human plasma: selectivity issue, impact assessment and resolution.

Ronald de Vries graduated in Organic and Analytical Chemistry at the Free University of Amsterdam, The Netherlands. After working in a Contract Laboratory (CRO) for 7 years, he joined Janssen R&D in 1998. At Janssen R&D, Belgium, Ronald worked in the bioanalytical department that supports both clinical and nonclinical bioanalysis.

A comparison between direct and indirect measurements of neurotransmitter vesicle release dynamics: a computational study.

Presynaptic vesicular release of neurotransmitters is a stochastic process involving complex mechanisms triggered by an elevation of calcium concentration. The mechanisms behind neurotransmitters release play a critical role in synaptic function and plasticity. Understanding its properties, both in term of its dynamics and its underlying mechanisms, may therefore help further our understanding of synaptic plasticity.

Bioanalysis of chiral compounds during drug development using a tiered approach.

Significant differences in the pharmacodynamic activity and pharmacokinetic properties could exist for a pair of enantiomeric drugs. In order to evaluate the activity, toxicity, absorption, distribution, metabolism, and excretion properties of the individual enantiomers, and any potential for chiral inversion caused by the biotransformation process, chiral bioanalytical assays are necessary for individual enantiomers and/or their metabolites for in vivo samples. However, development and validation of chiral quantitative assays are highly challenging in comparison to typical nonchiral assays.

Risk factors for hypertensive crisis: importance of out-patient blood pressure control.

Objectives: The purpose of this study was to identify independent risk factors for development of hypertensive crisis.

Methods: This was a retrospective, case-controlled study. Cases were 143 patients who presented during a 3-year period to the Emergency Department with the diagnosis of hypertensive crisis, defined as systolic pressure >/=180 mmHg and/or diastolic pressure >/=110 mmHg and symptoms of hypertensive emergency during the Emergency Department presentation.