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Do P-glycoprotein-mediated drug-drug interactions at the blood-brain barrier impact morphine brain distribution?

J Pharmacokinet Pharmacodyn

January 2025

Division of Systems Pharmacology and Pharmacy, Leiden Academic Center for Drug Research, Leiden University, Einsteinweg 55, Leiden, 2333 CC, The Netherlands.

P-glycoprotein (P-gp) is a key efflux transporter and may be involved in drug-drug interactions (DDIs) at the blood-brain barrier (BBB), which could lead to changes in central nervous system (CNS) drug exposure. Morphine is a P-gp substrate and therefore a potential victim drug for P-gp mediated DDIs. It is however unclear if P-gp inhibitors can induce clinically relevant changes in morphine CNS exposure.

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Trophoblast cell-surface antigen 2 (TROP 2) has re-emerged as a promising biomarker in triple-negative breast cancer (TNBC), with high overexpression in many TNBC cases. However, despite its potential and approval as an antibody-drug-conjugate for TNBC treatment, TROP 2-targeted delivery systems are currently underexplored. Therefore, this study was aimed at exploiting the potential of TROP 2 targeting by encapsulating metformin (Met), an antidiabetic drug associated with tumor growth inhibitory properties, inside liposomes decorated with TROP 2-targeting single-chain variable fragments (scFvs).

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The reasons for the low frequency of anti-Ro/SS-A antibody in patients with HTLV-1-associated myelopathy complicated with Sjögren's syndrome (SS) are unclear. In this study, we investigated whether HTLV-1-infected T cells can act directly on B cells and suppress B cells' production of antibodies, including anti-Ro/SS-A antibody. For this purpose, we established an in vitro T-cell-free B-cell antibody production system.

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This paper examines the impact of environmental management system (EMS) certification, a significant voluntary participatory environmental regulation, on the risk of stock price collapse. The study is based on sample data of heavily polluting listed companies from 2008-2020. The study demonstrates that certification of environmental management systems has a significant impact on preventing share price collapse.

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Maternally activated connections of the ventral lateral septum reveal input from the posterior intralaminar thalamus.

Brain Struct Funct

January 2025

Department of Physiology and Neurobiology, Laboratory of Molecular and Systems Neurobiology, Eötvös Loránd University, Budapest, Hungary.

The lateral septum (LS) demonstrates activation in response to pup exposure in mothers, and its lesions eliminate maternal behaviors suggesting it is part of the maternal brain circuitry. This study shows that the density of pup-activated neurons in the ventral subdivision of the LS (LSv) is nearly equivalent to that in the medial preoptic area (MPOA), the major regulatory site of maternal behavior in rat dams. However, when somatosensory inputs including suckling were not allowed, pup-activation was markedly reduced in the LSv.

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