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Structural and biophysical analysis of cytochrome P450 2C9*14 and *27 variants in complex with losartan.
J Inorg Biochem
September 2024
Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, 106 New Scotland Avenue, Albany, NY 12208, USA. Electronic address:
The human cytochrome P450 (CYP) 1, 2 and 3 families of enzymes are responsible for the biotransformation of a majority of the currently available pharmaceutical drugs. The highly polymorphic CYP2C9 predominantly metabolizes many drugs including anticoagulant S-warfarin, anti-hypertensive losartan, anti-diabetic tolbutamide, analgesic ibuprofen, etc. There are >80 single nucleotide changes identified in CYP2C9, many of which significantly alter the clearance of important drugs.
View Article and Find Full Text PDFSimultaneous TIRF imaging of subplasmalemmal Ca dynamics and granule fusions in insulin-secreting INS-1 cells reveals coexistent synchronized and asynchronous release.
Cell Calcium
June 2024
Leipzig University, Rudolf-Boehm-Institute of Pharmacology and Toxicology, Härtelstraße 16-18, Leipzig 04107, Germany. Electronic address:
The basal and glucose-induced insulin secretion from pancreatic beta cells is a tightly regulated process that is triggered in a Ca-dependent fashion and further positively modulated by substances that raise intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP) or by certain antidiabetic drugs. In a previous study, we have temporally resolved the subplasmalemmal [Ca] dynamics in beta cells that are characterized by trains of sharply delimited spikes, reaching peak values up to 5 µM. Applying total internal reflection fluorescence (TIRF) microscopy and synaptopHluorin to visualize fusion events of individual granules, we found that several fusion events can coincide within 50 to 150 ms.
View Article and Find Full Text PDFInvestigation of the drug-drug interaction and incompatibility mechanism between Aconitum carmichaelii Debx and Pinellia ternata (Thunb.) Breit.
J Ethnopharmacol
August 2024
State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Haihe Laboratory of Modern Chinese Medicine, 301617, Tianjin, China. Electronic address:
Ethnopharmacological Relevance: The combination of Aconitum carmichaelii Debx (Chuanwu, CW) and Pinellia ternata (Thunb.) Breit (Banxia, BX) forms an herbal pair within the eighteen incompatible medicaments (EIM), indicating that BX and CW are incompatible. However, the scientific understanding of this incompatibility mechanism, especially the corresponding drug-drug interaction (DDI), remains complex and unclear.
View Article and Find Full Text PDFTailoring the release of drugs having different water solubility by hybrid polymer-lipid microparticles with a biphasic structure.
Eur J Pharm Biopharm
September 2023
Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Via S. Donato 19/2, Bologna 40127, Italy.
The aim of this study is to investigate the potential of hybrid polymer-lipid microparticles with a biphasic structure (b-MPs) as drug delivery system. Hybrid b-MPs of Compritol®888 ATO as main lipid constituent of the shell and polyethylene glycol 400 as core material were produced by an innovative solvent-free approach based on spray congealing. To assess the suitability of hybrid b-MPs to encapsulate various types of APIs, three model drugs (fluconazole, tolbutamide and nimesulide) with extremely different water solubility were loaded into the polymeric core.
View Article and Find Full Text PDFEvaluation of mRNA markers in differentiating human SH-SY5Y cells for estimation of developmental neurotoxicity.
Neurotoxicology
July 2023
Department of Biochemistry and Biophysics, Stockholm University, 106 91 Stockholm, Sweden. Electronic address:
Current guidelines for developmental neurotoxicity (DNT) evaluation are based on animal models. These have limitations so more relevant, efficient and robust approaches for DNT assessment are needed. We have used the human SH-SY5Y neuroblastoma cell model to evaluate a panel of 93 mRNA markers that are frequent in Neuronal diseases and functional annotations and also differentially expressed during retinoic acid-induced differentiation in the cell model.
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