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Identification of novel inhibitors of rat Mrp3. KU Leuven

Tom De Vocht, Christophe Buyck, Neel Deferm, Bing Qi, Pieter Van Brantegem, Herman van Vlijmen, Jan Snoeys, Eef Hoeben, An Vermeulen, Pieter Annaert, et al.
Multidrug resistance-associated protein (MRP; ABCC gene family) mediated efflux transport plays an important role in the systemic and tissue exposure profiles of many drugs and their metabolites, and also of endogenous compounds like bile acids and bilirubin conjugates. However, potent and isoform-selective inhibitors of the MRP subfamily are currently lacking. Therefore, the purpose of the present work was to identify novel rat Mrp3 inhibitors. ...

Ventilator-associated bacterial pneumonia in coronavirus 2019 disease, a retrospective monocentric cohort study Vrije Universiteit Brussel

Marco Moretti, Johan Van Laethem, Andrea Minini, Denis Pierard, Manu L N G Malbrain

INTRODUCTION: Severe coronavirus 2019 disease (CoViD-19) may lead to respiratory failure and mechanical ventilation. Therefore, ventilator associated pneumonia (VAP) may complicate the course of the disease. The aim of the current article was to investigate possible predictive factors for bacterial VAP on a retrospective manner, in a cohort of mechanically ventilated CoViD-19 patients. Additionally, determinant factors of lethality were ...

Exploring the Impact of Intestinal Fluid Components on the Solubility and Supersaturation of Danazol KU Leuven

Cecilie Maria Madsen, Jakob Plum, Bart Hens, Patrick Augustijns, Anette Müllertz, Thomas Rades
Eleven simulated intestinal fluids (SIF) were designed using a Design of Experiment (DoE) approach. The DoE SIF covered a range of compositions of fasted state human intestinal fluid (FaHIF) with regard to pH, bile salt (BS), and phospholipid (PL). Using the model compound danazol, the apparent crystalline solubility (aCS) and apparent amorphous solubility (aAS), as well as the supersaturation propensity was determined in the DoE SIF media. The ...

The effect of xenon on fetal neurodevelopment following maternal sevoflurane anesthesia and laparotomy in rabbits. KU Leuven

Sarah Devroe, Lennart Van Der Veeken, Tom Bleeser, Johannes van der Merwe, Roselien Meeusen, Marc Van De Velde, Jan Deprest, Steffen Rex
BACKGROUND: There is concern that maternal anesthesia during pregnancy impairs brain development of the human fetus. Xenon is neuroprotective in pre-clinical models of anesthesia-induced neurotoxicity in neonates. It is not known if xenon also protects the developing fetal brain when administered in addition to maternal sevoflurane-anesthesia during pregnancy. OBJECTIVE: To investigate the effects of sevoflurane and xenon on neurobehaviour and ...

A comprehensive review on non-clinical methods to study transfer of medication into breast milk - A contribution from the ConcePTION project KU Leuven

Nina Nauwelaerts, Neel Deferm, Anne Smits, Chiara Bernardini, Bart Lammens, Peggy Gandia, Alice Panchaud, Hedvig Nordeng, Maria Laura Bacci, Monica Forni, et al.
Breastfeeding plays a major role in the health and wellbeing of mother and infant. However, information on the safety of maternal medication during breastfeeding is lacking for most medications. This leads to discontinuation of either breastfeeding or maternal therapy, although many medications are likely to be safe. Since human lactation studies are costly and challenging, validated non-clinical methods would offer an attractive alternative. ...

Ontogeny of Hepatic Transporters and Drug-Metabolizing Enzymes in Humans and in Nonclinical Species KU Leuven

BD van Groen, J Nicolai, AC Kuik, S Van Cruchten, E van Peer, Anne Smits, S Schmidt, SN de Wildt, Karel Allegaert, L De Schaepdrijver, et al.
The liver represents a major eliminating and detoxifying organ, determining exposure to endogenous compounds, drugs, and other xenobiotics. Drug transporters (DTs) and drug-metabolizing enzymes (DMEs) are key determinants of disposition, efficacy, and toxicity of drugs. Changes in their mRNA and protein expression levels and associated functional activity between the perinatal period until adulthood impact drug disposition. However, ...

Human hepatic in vitro models reveal distinct anti-NASH potencies of PPAR agonists Vrije Universiteit Brussel

Joost Boeckmans, Alessandra Natale, Matthias Rombaut, Karolien Buyl, Brent Cami, Veerle Rita J De Boe, Anja Heymans, Vera Rogiers, Joery De Kock, Tamara Vanhaecke, et al.

Non-alcoholic steatohepatitis (NASH) is a highly prevalent, chronic liver disease characterized by hepatic lipid accumulation, inflammation, and concomitant fibrosis. Up to date, no anti-NASH drugs have been approved. In this study, we reproduced key NASH characteristics in vitro by exposing primary human hepatocytes (PHH), human skin stem cell-derived hepatic cells (hSKP-HPC), HepaRG and HepG2 cell lines, as well as LX-2 cells to multiple ...

Evaluation of the dioxin-like toxicity in soil samples from Thua Thien Hue province using the AhR-CALUX bioassay - An update of Agent Orange contamination in Vietnam Vrije Universiteit Brussel

Tran Thi Ai My, Nguyen Duy Dat, Kersten Van Langenhove, Michael S Denison, Hoang Thai Long, Marc Elskens

In this study, an AhR-responsive reporter-gene cell-based bioassay CALUX was used to assess the biological potency of dioxins and dioxin-like PCBs (dl-PCBs) in top soil samples collected from a former airbase (A-So) and remote regions from urban and agricultural areas in Thua Thien Hue, Vietnam. In top soil collected from A-So airbase, Bioanalytical EQuivalent (BEQ) concentrations of up to 2700 pg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) ...

Impact of gastrointestinal tract variability on oral drug absorption and pharmacokinetics: An UNGAP review. KU Leuven

Zahari Vinarov, Mohammad Abdallah, José AG Agundez, Karel Allegaert, Abdul W Basit, Marlies Braeckmans, Jens Ceulemans, Maura Corsetti, Brendan T Griffin, Michael Grimm, et al.
The absorption of oral drugs is frequently plagued by significant variability with potentially serious therapeutic consequences. The source of variability can be traced back to interindividual variability in physiology, differences in special populations (age- and disease-dependent), drug and formulation properties, or food-drug interactions. Clinical evidence for the impact of some of these factors on drug pharmacokinetic variability is ...

Generation-specific and interactive effects of pesticide and antidepressant exposure in a fish model call for multi-stressor and multigenerational testing KU Leuven

Eli Thoré, Floor Van Hooreweghe, Charlotte Philippe, Luc Brendonck, Tom Pinceel
Ecological risks of a pollutant are typically assessed via short-term exposure of model organisms to that single compound. Such tests are informative, but cannot ascertain effects of long-term and multigenerational mixed-stressor exposure with which organisms are often confronted in their natural environment. Therefore, full life-cycle and multigenerational tests are needed. Yet, these are hampered due to long lifespans and generation times of ...