Simultaneous isotyping and semi-quantitation of anti-drug antibodies to an IgG1 biotherapeutic using hybrid LBA-LC-MS/MS.

Background: Commonly, ligand-binding platforms are being used for immunogenicity assessment, but with the recent advent of liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) for protein quantification, this technology has become an alternative for the measurement of anti-drug antibodies (ADAs), when combined with an immunocapture step to extract them out of the biological sample.

Method: The monoclonal antibody adalimumab was immobilized on magnetic beads to isolate ADAs against this drug from serum samples. Multiple repetitions of immunopurification were used to minimize nonspecific binding and improve drug tolerance while maintaining sufficient recovery.

Comparing anti-drug antibody signal-to-noise ratios to assess immunogenicity and interchangeability in adalimumab biosimilar studies.

Background: To support an interchangeability designation for Sandoz adalimumab biosimilar (GP2017), antidrug antibody (ADA) signal-to-noise (S/N) ratios were assessed in the GP2017 ADACCESS trial to directly assess potential changes in immunogenicity.

Research Design And Methods: ADACCESS was a 51-week trial in patients with moderate-to-severe plaque psoriasis that included patients treated continuously with reference adalimumab (cH), and patients who experienced four switches between reference adalimumab and GP2017 (H2H). ADAs were measured every 6 weeks during the switching phase using an electrochemiluminescence assay.

Human Endothelial Cell Seeding in Partially Decellularized Kidneys.

The excessive demand for organ transplants has promoted the development of strategies that increase the supply of immune compatible organs, such as xenotransplantation of genetically modified pig organs and the generation of bioartificial organs. We describe a method for the partial replacement of rat endothelial cells for human endothelial cells in a rat's kidney, obtaining as a final result a rat-human bioartificial kidney. First, in order to maintain parenchymal epithelial cells and selectively eliminate rat endothelial cells, three methods were evaluated in which different solutions were perfused through the renal artery: 0.

Secretory Leukocyte Proteinase Inhibitor Protects Acute Kidney Injury Through Immune and Non-Immune Pathways.

Acute kidney injury (AKI) is characterized by rapid loss of excretory function and is the clinical manifestation of several disorders affecting the kidney. The aim of the present study was to investigate the mechanism of action of Secretory Leukocyte Proteinase Inhibitor (SLPI) that protects the kidneys form AKI. In vivo and in vitro experiments were performed to assess the effect of SLPI on kidney injury.

In vitro characterization of new psychoactive substances at the μ-opioid, CB1, 5HT, and 5-HT receptors-On-target receptor potency and efficacy, and off-target effects.

New psychoactive substances (NPS) appear on the recreational market on a monthly basis, with unclear toxicology, resulting in an increasing number of fatalities. Identification of drug targets and potencies is crucial for understanding and treating intoxications and for scheduling processes. In this study 60 NPS and metabolites belonging to opioids, cannabinoids and serotonergic hallucinogens classes were screened for in vitro activation of the μ-opioid, CB1, 5-HT and 5-HT receptors using the AequoZen cell system.

Evidence of scavenging behaviour in crested porcupine.

The vegetarian diet of many herbivorous mammals is supplemented with proteins of animal origin, especially in young individuals and in breeding females, to provide key proteins necessary for both growth and breeding. Among porcupine species, only the Cape porcupine (Hystrix africaeaustralis) has been observed to consume carrion flesh. From June to August 2019, a pigeon carcass was placed together with corn in 7 study settlements and near 2 monitored capture-traps, in order to assess the carrion flesh feeding habits of the crested porcupine (Hystrix cristata).

Muscle satellite cells and impaired late stage regeneration in different murine models for muscular dystrophies.

Satellite cells (SCs) are the main muscle stem cells responsible for its regenerative capacity. In muscular dystrophies, however, a failure of the regenerative process results in muscle degeneration and weakness. To analyze the effect of different degrees of muscle degeneration in SCs behavior, we studied adult muscle of the dystrophic strains: DMD, Large, DMD/Large, with variable histopathological alterations.

SLPI in the perfusion solution helps to identify graft quality in kidney transplants.

It is important to find biomarkers that identify the graft quality in kidney transplantation. The level of SLPI in the cold preservation solution was used as a marker to predict early kidney graft function after transplantation. Before transplantation, kidneys were washed and SLPI was measured in the discarded solution.

Critical Role of Monocyte Recruitment in Optic Nerve Damage Induced by Experimental Optic Neuritis.

Neuroinflammatory diseases are characterized by blood-brain barrier disruption (BBB) and leukocyte infiltration. We investigated the involvement of monocyte recruitment in visual pathway damage provoked by primary optic neuritis (ON) induced by a microinjection of bacterial lipopolysaccharide (LPS) into the optic nerve from male Wistar rats. Increased Evans blue extravasation and cellularity were observed at 6 h post-LPS injection.

Validation and Cross-Reactivity Data for Fentanyl Analogs With the Immunalysis Fentanyl ELISA.

Every year new fentanyl analog compounds, or fentanyls, appear on the drug scene. Development of immunoassays dedicated for screening individual molecules is challenging due to the short-lived presence of these compounds on the recreational drug market. Therefore, we investigated the detecting capabilities of the immunalysis fentanyl direct enzyme-linked immunosorbent assay (ELISA) kit against fentanyl in whole blood, and determined the cross-reactivity of nine fentanyl analogs (2-fluorofentanyl, acetylfentanyl, acrylfentanyl, carfentanil, cyclopropylfentanyl, tetrahydrofuranylfentanyl, furanylfentanyl, ocfentanil, valerylfentanyl) to confirm its validity for the general screening of fentanyls.

Fatal Poisonings Associated with New Psychoactive Substances.

This chapter describes how new psychoactive substances (NPS) have been involved in fatal intoxications from 2010 and onwards. It summarizes the circumstances, antemortem symptoms, and adverse effects that have led to death after ingestion of one or more NPS and tabulates concentrations, and postmortem findings from these intoxications.Consumption of NPS exerts health problems and unknown risks for the users.

Extraocular muscle sampled volume in Graves' orbitopathy using 3-T fast spin-echo MRI with iterative decomposition of water and fat sequences.

Background: Current magnetic resonance imaging (MRI) techniques for measuring extraocular muscle (EOM) volume enlargement are not ideally suited for routine follow-up of Graves' ophthalmopathy (GO) because the difficulty of segmenting the muscles at the tendon insertion complicates and lengthens the study protocol.

Purpose: To measure the EOM sampled volume (SV) and assess its correlation with proptosis.

Material And Methods: A total of 37 patients with newly diagnosed GO underwent 3-T MRI scanning with iterative decomposition of water and fat (IDEAL) sequences with and without contrast enhancement.

Cementoin-SLPI fusion protein binds to human monocytes and epithelial cells and shows higher biological activity than SLPI.

Secretory Leukocyte Proteinase Inhibitor (SLPI) is an antiinflammatory peptide that blocks the activity of serine proteases, primarily the neutrophil elastase. In an attempt to direct the activity of SLPI on inflamed sites, a chimera consisting of the transglutaminase II substrate domain of trappin 2 (cementoin), and the mature SLPI protein was constructed. Cell attachment and biological activity were compared between SLPI and this chimera.

Alpha Lipoic Acid: A Therapeutic Strategy that Tend to Limit the Action of Free Radicals in Transplantation.

Organ replacement is an option to mitigate irreversible organ damage. This procedure has achieved a considerable degree of acceptance. However, several factors significantly limit its effectiveness.

Effects of contrast-enhancement on diffusion weighted imaging and apparent diffusion coefficient measurements in 3-T magnetic resonance imaging of breast lesions.

Background The effect of gadolinium-based contrast agents on diffusion-weighted imaging (DWI) measurements of breast lesions is still not clear. Purpose To investigate gadolinium effects on DWI and apparent diffusion coefficient (ADC) in breast lesions and normal parenchyma with 3 Tesla contrast-enhanced MRI. Material and Methods Pre- and post-contrast DWI (b = 0 and b = 1000 s/mm) were acquired in 47 patients.

High-resolution MR lymphangiography for planning lymphaticovenous anastomosis treatment: a single-centre experience.

Purpose: This article illustrates the feasibility of MR lymphangiography (MRL) for imaging lymphatic vessels in patients with lymphedema, its accuracy in distinguishing lymphatic vessels from veins, and its utility for planning Lymphaticovenous anastomosis (LVA) treatment.

Materials And Methods: We prospectively enrolled 30 patients (24 women, range 18-70, 17 cases of lower limb lymphedema, 6 cases of primary lymphedema). All the patients underwent MRL, using a 1.

Acrylfentanyl: Another new psychoactive drug with fatal consequences.

The European Nordic Countries are the most exposed to opioid-related deaths. Between April and October 2016, a series of forty lethal intoxications occurred in Sweden, in which the presence of the synthetic opioid acrylfentanyl was determined to be the main - or a contributing - cause of death. In the reported cases, the blood concentration of acrylfentanyl - mostly detected in combination with other drugs - ranged from 0.

MRI rare finding: Absence of the left liver lobe.

We report a rare case of left liver lobe absence in an 80-year-old male patient discovered during an MRI scan. The main imaging features of this condition are briefly reviewed, together with its pathogenesis and the most common associations and differential diagnoses.

MR Lymphangiography: A Practical Guide to Perform It and a Brief Review of the Literature from a Technical Point of View.

We propose a practical approach for performing high-resolution MR lymphangiography (MRL). We shall discuss and illustrate the technical approach for the visualization of lymphatic vessels in patients suffering from lymphedema, how to distinguish lymphatic vessels from veins, and MRL role in supermicrosurgery treatment planning. A brief review of literature, from a technical point of view, is also reported.

Exercise in a Pill: The Latest on Exercise-Mimetics.

There is increasing evidence that an active lifestyle benefits both body and brain. However, not everyone may be able to exercise due to disease, injury or aging-related frailty. Identification of cellular targets activated by physical activity may lead to the development of new compounds that can, to some extent, mimic systemic and central effects of exercise.

Postmortem and Toxicological Findings in a Series of Furanylfentanyl-Related Deaths.

Over the course of 4 months in 2015 and 2016, a cluster of seven fatal intoxications involving the opioid-analogue furanylfentanyl occurred in Sweden; toxicological analysis showed presence of furanylfentanyl either as the only drug or in combination with other illicit substances. Previous publications have only reported non-lethal furanylfentanyl intoxications. In the cases presented here, furanylfentanyl intoxication-alone or in combination with other drugs-was determined to be the cause of death by the responsible pathologist.

Role of 3.0 Tesla magnetic resonance hysterosalpingography in the diagnostic work-up of female infertility.

Background: Imaging evaluation plays a crucial role in the diagnostic work-up of female infertility. In recent years, the possibility to evaluate tubal patency using 1.5 Tesla magnetic resonance (1.