Enzyme-mediated drug-drug interactions: a review of and methodologies, regulatory guidance, and translation to the clinic.

Enzyme-mediated pharmacokinetic drug-drug interactions can be caused by altered activity of drug metabolizing enzymes in the presence of a perpetrator drug, mostly inhibition or induction. We identified a gap in the literature for a state-of-the art detailed overview assessing this type of DDI risk in the context of drug development. This manuscript discusses and methodologies employed during the drug discovery and development process to predict clinical enzyme-mediated DDIs, including the determination of clearance pathways, metabolic enzyme contribution, and the mechanisms and kinetics of enzyme inhibition and induction.

Expression profile of the entire detoxification gene inventory of the western honeybee, Apis mellifera across life stages.

The western honeybee, Apis mellifera, is a managed pollinator of many crops and potentially exposed to a wide range of foreign compounds, including pesticides throughout its life cycle. Honeybees as well as other insects recruit molecular defense mechanisms to facilitate the detoxification of xenobiotic compounds. The inventory of detoxification genes (DETOXome) is comprised of five protein superfamilies: cytochrome P450 monooxygenases (P450), carboxylesterases, glutathione S-transferases (GST), UDP-glycosyl transferases (UGT) and ATP-binding cassette (ABC) transporters.

The Smk1 MAPK and Its Activator, Ssp2, Are Required for Late Prospore Membrane Development in Sporulating .

During sporulation in the budding yeast , proper development of the prospore membrane is necessary for the formation of viable spores. The prospore membrane will eventually become the plasma membrane of the newly formed haploid spore and also serves as the template for the deposition of the spore wall. The prospore membrane is generated de novo during meiosis II and the growing edge of the prospore membrane is associated with the Leading Edge Protein (LEP) complex.

A simple method to estimate flow restriction for dual ventilation of dissimilar patients: The BathRC model.

Background: With large numbers of COVID-19 patients requiring mechanical ventilation and ventilators possibly being in short supply, in extremis two patients may have to share one ventilator. Careful matching of patient ventilation requirements is necessary. However, good matching is difficult to achieve as lung characteristics can have a wide range and may vary over time.

Toll-like receptor 2-deficiency on bone marrow-derived cells augments vascular healing of murine arterial lesions.

Aims: Neointimal hyperplasia contributes to arterial restenosis after percutaneous transluminal coronary angioplasty or vascular surgery. Neointimal thickening after arterial injury is determined by inflammatory processes. We investigated the role of the innate immune receptor toll-like receptor 2 (TLR2) in neointima formation after arterial injury in mice.