Sympathetic stimulation with norepinephrine may come at a cost

<正>Norepinephrine (NE; also known as noradrenaline) is the body's primary adrenergic neurotransmitter which belongs to the catecholamine family. Norepinephrine has pharmacologic effects on theα1 (Suita et al.,2015),α2 (Schwartz,1997),β1,β2 andβ3(Tsukada et al., 2003) adrenoceptors. In the brain, norepinephrine increases arousal and alertness, promotes vigilance, enhances formation and retrieval of memory, and focuses attention. It also increases restlessness and anxiety. In the remainder of the body,     

An evaluation of empagliflozin and it’s applicability to hypertension as a therapeutic option

ABSTRACT

Introduction

Sodium-glucose cotransporter 2 (SGLT2) inhibitors such as Empagliflozin are novel antihyperglycemic drugs approved for the treatment of type 2 diabetes (T2D). In addition to its glucose-lowering effects, Empagliflozin promotes weight loss, blood pressure reduction, and other beneficial metabolic benefits.     

Liquid Crystalline Esters of Dibenzophenazines

A series of esters of 2,3,6,7-tetrakis(hexyloxy)dibenzo[a,c]phenazine-11-carboxylic acid was prepared in order to probe the effects of the ester groups on the liquid crystalline behavior. These compounds exhibit columnar hexagonal phases over broad temperature ranges. Variations in chain length, branching, terminal groups, and the presence of cyclic groups were found to modify transition temperatures without substantially destabilizing the mesophase range.     

Direct effect on validity of response run-in selection in clinical trials

A run-in is a period prior to randomization during which potential participants who have met all entry criteria for a randomized clinical trial are assigned the same regimen, either the control (possibly placebo) or the experimental treatment. Typically, the intention is to exclude from the subsequent study (i.e., randomization) some segment of this cohort, based on their experiences during the run-in period. Selecting patients based on the run-in thereby forces differential representation of certain subpopulations relative to others. Previous studies have addressed the potential for a run-in to jeopardize validity through unintended mechanisms. While these concerns are valid, they leave open the possibility that modifications to the design of the run-in might be able to preserve validity, even if patient selection is based on the results of the run-in. As such, we address the potential for selecting patients based on response during a run-in period to jeopardize validity directly, through its intended effect of overrepresenting (relative to the screened population) some segments in the randomized portion of the trial and underrepresenting others.     

Characterization of 107 genomic DNA reference materials for CYP2D6, CYP2C19, CYP2C9, VKORC1, and UGT1A1: a GeT-RM and Association for Molecular Pathology collaborative project

Pharmacogenetic testing is becoming more common; however, very few quality control and other reference materials that cover alleles commonly included in such assays are currently available. To address these needs, the Centers for Disease Control and Prevention's Genetic Testing Reference Material Coordination Program, in collaboration with members of the pharmacogenetic testing community and the Coriell Cell Repositories, have characterized a panel of 107 genomic DNA reference materials for five loci (CYP2D6, CYP2C19, CYP2C9, VKORC1, and UGT1A1) that are commonly included in pharmacogenetic testing panels and proficiency testing surveys. Genomic DNA from publicly available cell lines was sent to volunteer laboratories for genotyping. Each sample was tested in three to six laboratories using a variety of commercially available or laboratory-developed platforms. The results were consistent among laboratories, with differences in allele assignments largely related to the manufacturer's assay design and variable nomenclature, especially for CYP2D6. The alleles included in the assay platforms varied, but most were identified in the set of 107 DNA samples. Nine additional pharmacogenetic loci (CYP4F2, EPHX1, ABCB1, HLAB, KIF6, CYP3A4, CYP3A5, TPMT, and DPD) were also tested. These samples are publicly available from Coriell and will be useful for quality assurance, proficiency testing, test development, and research.