Evaluation of immunosuppression in a murine model of respiratory syncytial virus (RSV) infection

ERS Congress 2024 -- Respiratory syncytial virus (RSV) is a major global pathogen, predominantly affecting infants, often leading to bronchiolitis and lower respiratory tract disease (LRTD). RSV is mainly replicated in respiratory ciliated epithelium and analysis of patient samples with severe RSV has shown significantly elevated neutrophil and macrophage content, enriched with pro-inflammatory cytokines such as TNFα, IL-6, IL-1a, IL-8, IL-9, IL-10 and IL-17, which impact the pathogenesis of RSV infection. Currently there are no licensed vaccines for this pathogen, and therefore the implementation of functional animal models for studying this virus is of high importance. This study aimed to establish a murine model of RSV infection, which induced clinical signs and inflammatory responses representative of human RSV infection.

Further exploring the automated touchscreen-based mCANTAB device: Testing for motor precision and employing a self-ordered spatial search paradigm

Eurotox 2024 -- In the early stages of developing drugs that affect the central nervous system, regulatory authorities often request an examination to understand whether the new drug might affect cognitive function or development. We have conducted a study that evaluated the effect of scopolamine (used as a reference compound), on simple discrimination (SD) tasks, which caused learning impairment, as expected. In this study, we reported two additional investigations. First, we investigated the precision of touch responses as a potential influence on discrimination performance by evaluating the effect of target size on the performance of animals. Second, we assessed whether the self-ordered spatial search (SOSS) paradigm task can be trained under these experimental conditions in parallel to the main discrimination tasks. The period of training was defined by success in discrimination tasks, with the SOSS paradigm trained as feasible within this period. 

Integrated micronucleus and multi-endpoint screen for identification and classification of in vitro genotoxicants

EMGS 2024 -- Screening for in vitro genotoxicity can remove potential hazards and identify lead candidates early in development. The in vitro micronucleus (IVMN) assay is routinely used to screen compounds for induction of chromosome damage with low compound requirement and faster turnaround times. However, micronucleus induction can arise via non-DNA reactive modes of actions, which can be important information when identifying compounds for further development. The in vitro MultiFlow® assay is a multiplexed flow cytometric based assay for prediction of genotoxic mode of action (clastogenic, aneugenic or non-genotoxic) based on changes in ɣH2AX, p53, phospo-histone H3 (pHH3) and polyploidy. Integrating IVMN and MultiFlow® endpoints can provide genotoxic mode of action information and better understanding of any apparent genotoxic response. Human TK6 cells were exposed to known clastogens, aneugens and non-genotoxicants and analysed at 4 and 24 hours for compound-induced changes in p53, ɣH2AX, phospo-histone H3 and polyploidy using the MultiFlow® assay and at 24 hours for induction of micronuclei (MN).

Labcorp to Acquire Select Outreach Services from Ballad Health

Transfer of outreach services brings enhanced global resources to region, including expanded access to advanced testing, innovative digital tools for improved patient experience and achieves Ballad Health’s goal of continuing to lower the cost of health care JOHNSON CITY, Tenn.

Method qualification for the preparation of PBMC cells from human blood with a view to evaluate safety, tolerability, dosimetry and preliminary activity of radioligands on cancer patients

DMDG Open 2024 -- Peripheral blood mononuclear cell (PBMC) isolation is a widely used technique within clinical analysis. Their isolation leads to a host of downstream applications, including measurement of biomarkers and measurement of the immune response to a given treatment. Preparation of human PBMC cells from blood samples containing radioligands are required to support multisite clinical trials (a Phase I, open-label, multi-centre study). This study involved collaboration across both our US and UK sites and the qualification of the human PBMC method was adapted from that used at the Labcorp Madison facility to isolate animal PBMCs. The ultimate aim of this study was to demonstrate method robustness and produce the required yield of PBMC cells to support subsequent clinical analysis by ensuring reproducibility of the method and enabling any modifications to account differences of equipment between sites. Furthermore, the US team also investigated the effects of processing at set times post-blood draw to simulate the effects of the shipping process from multiple sites and the effects this had on PBMC yield.

Microautoradiography: Developing a future service

DMDG Open 2024 -- Microautoradiography (mARG), a complimentary service to whole-body autoradiography which allows the visualization of radioactivity to the cellular level, has been a service offering at Labcorp for over 30 years. There have been several changes in the supply of the nuclear emulsion, which is critical for the technique. Supply of commercial material was reasonable, if intermittent, as it was a supply-and-demand product. Suppliers ceased production of nuclear emulsion and in April 2023, the final manufacturer known to produce nuclear emulsion ceased production and dismantled their equipment. Our options were to find another supplier, stop offering the service or use an alternative product. As nothing was available commercially, could nuclear emulsion be prepared in-house and be a suitable alternative?

A retrospective analysis of non-specific binding in in vitro metabolism assays: Impact of protein and drug concentration on microsomal free fraction

DMDG Open 2024 -- Non-specific binding of drugs to microsomes can profoundly influence the outcome of in vitro metabolism assays and represents a key consideration in the calculation of kinetic parameters associated with drug-drug interaction (DDI) investigations or in vitro-in vivo extrapolations based on scaling of intrinsic clearance data. Recent regulatory guidance documents advocate the determination of the microsomal free fraction (fumic) and recommend that protein concentrations “are usually less than 1 mg/mL” (FDA, 2020) or “should be minimised” (ICH, 2024). Labcorp cytochrome P450 inhibition investigations include the determination of the fumic parameter in our standard study design. In this retrospective review, we have collated data from 39 recent studies to identify the proportion of compounds which show significant binding at typical incubation concentrations and the protein and concentration dependency of this binding. These data can provide a better understanding of assay conditions where binding has a high impact and facilitates the potential streamlining of processes with regard to experimental complexity and timelines.

Evaluation and comparison of HµREL® and HEPATOPAC® hepatic co-culture test systems for the prediction of metabolic clearance and metabolite profiling

DMDG Open 2024 -- Understanding the metabolic clearance and metabolism of xenobiotics across species is important for ensuring appropriate toxicological data is obtained, and for the successful prediction of human pharmacokinetics. Obtaining reliable in vitro metabolic clearance data and assessing the metabolite profiles of metabolically stable compounds using traditional hepatocytes suspensions has been challenging due to limited enzyme stability. Several test systems now offer extended enzyme stability and incubation times to more accurately assess the metabolic stability of metabolic stable compounds. Here the HμREL® co‑cultured hepatic model, which offers primary cryopreserved hepatocytes cultured together with cells of a non-parenchymal, stromal type and the HEPATOPAC® co-cultured hepatic model, which form hepatocyte islands surrounded by supportive stromal cells, were assessed and compared.

Labcorp to Acquire Select Outreach Services From Ballad Health

Johnson City, Tenn. and BURLINGTON, N.C. , Sept. 9, 2024 --  Ballad Health announced today it has reached agreement on a strategic collaboration with Labcorp, a global leader of innovative and comprehensive laboratory services, to provide outreach laboratory services across the Appalachian Highlands region.