Acanthamoeba culbertsoni isolated from a water sample of El-Mahmoudia canal in Alexandria, was orally inoculated into a mouse model (200-400 amoebae/mouse) under different conditions. One week postinfection (P.I.), 20% of infected normoacidic mice and all animals received cimetidine or tetracycline prior to infection passed the parasite in their stools. One month P.I., 70% of cimetidine and 100% of tetracycline pretreated mice showed marked erosion in the intestinal mucosa and areas of necrosis with congestion in the brains, with trophozoites and cysts in both tissues. It is concluded that, normoacidic mice may be simply acting as paratenic hosts. In case of hypoacidity or altered normal flora, the intestinal tract was invaded by amoebae representing a new portal of entry for CNS infection.
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Mol Neurodegener
January 2025
Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA.
Gastrointestinal (GI) involvement in Lewy body diseases (LBDs) has been observed since the initial descriptions of patients by James Parkinson. Recent experimental and human observational studies raise the possibility that pathogenic alpha-synuclein (⍺-syn) might develop in the GI tract and subsequently spread to susceptible brain regions. The cellular and mechanistic origins of ⍺-syn propagation in disease are under intense investigation.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Clinical and Molecular Medicine (IKOM), Faculty of Medicine and Health Sciences, NTNU - Norwegian University of Science and Technology, Prinsesse Kristinas gt. 1, Trondheim, 7030, Norway.
Restoration of the intestinal epithelial barrier is crucial for achieving mucosal healing, the therapeutic goal for inflammatory bowel disease (IBD). During homeostasis, epithelial renewal is maintained by crypt stem cells and progenitors that cease to divide as they differentiate into mature colonocytes. Inflammation is a major effector of mucosal damage in IBD and has been found to affect epithelial stemness, regeneration and cellular functions.
View Article and Find Full Text PDFDrug Metab Dispos
January 2025
Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, Research Unit of PK-PD Based Bioactive Components and Pharmacodynamic Target Discovery of Natural Medicine of Chinese Academy of Medical Sciences, China Pharmaceutical University, Nanjing, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China. Electronic address:
Silybin, a milk thistle extract, is a flavonolignan compound with hepatoprotective effect. It is commonly used in dietary supplements, functional foods, and nutraceuticals. However, the metabolism of silybin has not been systematically characterized in organisms to date.
View Article and Find Full Text PDFDrug Metab Dispos
January 2025
Department of Pharmaceutics, University of Washington, Seattle, Washington. Electronic address:
Physiologically based pharmacokinetic (PBPK) modeling is a physiologically relevant approach that integrates drug-specific and system parameters to generate pharmacokinetic predictions for target populations. It has gained immense popularity for drug-drug interaction, organ impairment, and special population studies over the past 2 decades. However, an application of PBPK modeling with great potential remains rather overlooked-prediction of diarrheal disease impact on oral drug pharmacokinetics.
View Article and Find Full Text PDFDrug Metab Dispos
January 2025
Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington. Electronic address:
To further the development of an in vitro model that faithfully recapitulates drug disposition of orally administered drugs, we investigated the utility of human enteroid monolayers to simultaneously assess intestinal drug absorption and first-pass metabolism processes. We cultured human enteroid monolayers from 3 donors, derived via biopsies containing duodenal stem cells that were propagated and then differentiated atop permeable Transwell inserts, and confirmed transformation into a largely enterocyte population via RNA sequencing analysis and immunocytochemistry (ICC) assays. Proper cell morphology was assessed and confirmed via bright field microscopy and ICC imaging of tight junction proteins and other apically and basolaterally localized proteins.
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