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How Uremic Toxins Alter Atorvastatin Disposition: Molecular Mechanisms of Inhibition of the Enzyme CYP3A4.
Balkan Med J
January 2025
Department of Clinical Pharmacy, China Pharmaceutical University, School of Basic Medicine and Clinical Pharmacy, Nanjing, China.
Article Synopsis
- Uremic patients accumulate protein-bound uremic toxins (PBUTs), which alter drug metabolism by affecting the environment around liver cells and CYP450 enzymes.
- The study found that specific PBUTs like indoxyl sulfate (IS) and hippurate (HA) significantly inhibit the metabolism of atorvastatin (ATV), with IS being the most impactful, reducing ATV metabolism by over 50%.
- Results showed that the expression of the enzyme CYP3A4, critical for drug metabolism, was downregulated in the presence of uremic serum, leading to decreased ATV uptake and excretion due to effects on related signaling pathways.
Association between serum total indoxyl sulfate, intraperitoneal inflammation, and peritoneal dialysis technique failure: a 3-year prospective cohort study.
BMC Nephrol
December 2024
Head Doctor of the Dialysis Medical Center LLC, "Nephrocenter", Dovzhenka 3, Kyiv, 03057, Ukraine.
Background: The impact of protein-bound uremic toxins, specifically indoxyl sulfate (IS) on peritoneal dialysis (PD) complications remains controversial. This study aimed to explore the link between serum total IS (tIS) levels, proinflammatory cytokines in serum and peritoneal dialysis effluent (PDE), and PD technique survival.
Methods: In this prospective cohort study, 84 patients were followed up for three years and analyzed.
Self-propelling, protein-bound magnetic nanobots for efficient in vitro drug delivery in triple negative breast cancer cells.
Sci Rep
December 2024
Department of Pharmaceutical Chemistry, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, India.
The emergence of self-propelling magnetic nanobots represents a significant advancement in the field of drug delivery. These magneto-nanobots offer precise control over drug targeting and possess the capability to navigate deep into tumor tissues, thereby addressing multiple challenges associated with conventional cancer therapies. Here, Fe-GSH-Protein-Dox, a novel self-propelling magnetic nanobot conjugated with a biocompatible protein surface and loaded with doxorubicin for the treatment of triple-negative breast cancer (TNBC), is reported.
View Article and Find Full Text PDFPrednisolone pharmacokinetics in dogs with protein-losing enteropathy.
J Vet Intern Med
December 2024
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
Background: It is unknown if glucocorticoid malabsorption contributes to the approximate 50% treatment failure rate in dogs with protein-losing enteropathy (PLE).
Objective: To compare pharmacokinetics (PK) of orally administered prednisolone in dogs with PLE vs healthy controls.
Animals: Fourteen dogs with well-characterized PLE and 7 control dogs.
Clearance of Protein-Bound Uremic Toxins Using Anion Nanotraps with Record High Uptake.
ACS Appl Mater Interfaces
December 2024
College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310058, China.
Article Synopsis
- Traditional hemodialysis is often ineffective at removing protein-bound uremic toxins (PBUTs) like -cresyl sulfate and indoxyl sulfate due to their strong attachment to serum albumin, which can lead to cardiovascular issues.
- A new class of cationic polymeric networks, CPN-X6-CPN-X9, shows exceptional capabilities in removing these toxins, with CPN-X7 and CPN-X6 achieving maximum sorption capacities that surpass any previously known materials.
- CPN-X9, which is hydrophobic, displays impressive selectivity in experiments and is able to recycle effectively over five cycles while maintaining good compatibility with blood.
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