6 research outputs found
SCORHE:A novel and practical approach to video monitoring of laboratory mice housed in vivarium cage racks
The System for Continuous Observation of Rodents in Home-cage Environment (SCORHE) was developed to demonstrate the viability of compact and scalable designs for quantifying activity levels and behavior patterns for mice housed within a commercial ventilated cage rack. The SCORHE in-rack design provides day- and night-time monitoring with the consistency and convenience of the home-cage environment. The dual-video camera custom hardware design makes efficient use of space, does not require home-cage modification, and is animal-facility user-friendly. Given the systemâs low cost and suitability for use in existing vivariums without modification to the animal husbandry procedures or housing setup, SCORHE opens up the potential for the wider use of automated video monitoring in animal facilities. SCORHEâs potential uses include day-to-day health monitoring, as well as advanced behavioral screening and ethology experiments, ranging from the assessment of the short- and long-term effects of experimental cancer treatments to the evaluation of mouse models. When used for phenotyping and animal model studies, SCORHE aims to eliminate the concerns often associated with many mouse-monitoring methods, such as circadian rhythm disruption, acclimation periods, lack of night-time measurements, and short monitoring periods. Custom software integrates two video streams to extract several mouse activity and behavior measures. Studies comparing the activity levels of ABCB5 knockout and HMGN1 overexpresser mice with their respective C57BL parental strains demonstrate SCORHEâs efficacy in characterizing the activity profiles for singly- and doubly-housed mice. Another study was conducted to demonstrate the ability of SCORHE to detect a change in activity resulting from administering a sedative
LectinâLike Oxidized LowâDensity Lipoprotein Receptor 1 Inhibition in Type 2 Diabetes: Phase 1 Results
Background Blockade of the lectinâlike oxidized lowâdensity lipoprotein receptorâ1 (LOXâ1) is a potentially attractive mechanism for lowering inflammatory and lipid risk in patients with atherosclerosis. This study aims to assess the safety, tolerability, and target engagement of MEDI6570, a highâaffinity monoclonal blocking antibody to LOXâ1. Methods and Results This phase 1, firstâinâhuman, placeboâcontrolled study (NCT03654313) randomized 88 patients with type 2 diabetes to receive single ascending doses (10, 30, 90, 250, or 500âmg) or multiple ascending doses (90, 150, or 250âmg once monthly for 3âmonths) of MEDI6570 or placebo. Primary end point was safety; secondary and exploratory end points included pharmacokinetics, immunogenicity, free soluble LOXâ1 levels, and change in coronary plaque volume. Mean age was 57.6/58.1âyears in the single ascending doses/multiple ascending doses groups, 31.3%/62.5% were female, and mean type 2 diabetes duration was 9.7/8.7âyears. Incidence of adverse events was similar among cohorts. MEDI6570 exhibited nonlinear pharmacokinetics, with terminal halfâlife increasing from 4.6âdays (30âmg) to 11.2âdays (500âmg), consistent with targetâmediated drug disposition. Doseâdependent reductions in mean soluble LOXâ1 levels from baseline were observed (>66% at 4âweeks and 71.61â82.96% at 10âweeks in the single ascending doses and multiple ascending doses groups, respectively). After 3 doses, MEDI6570 was associated with nonsignificant regression of noncalcified plaque volume versus placebo (â13.45âmm3 versus â8.25âmm3). Conclusions MEDI6570 was well tolerated and demonstrated doseâdependent soluble LOXâ1 suppression and a pharmacokinetic profile consistent with onceâmonthly dosing. Registration URL: https://clinicaltrials.gov/; Unique identifier: NCT03654313