Retinal, vitreous humor, brain, and cerebrospinal fluid (CSF) foscarnet levels were measured by high-performance liquid chromatography after administration of an intravenous dose of 120 mg/kg of body weight to 32 pigmented rabbits. A pharmacokinetic analysis was done using a two-compartment model. The penetration ratios, defined as ratios of retinal, vitreous humor, brain, and CSF areas under the concentration-time curve from 0 to 2 h were 110% +/- 1%, 12.3% +/- 0.7%, 118% +/- 1%, and 20.2% +/- 2.2%, respectively. These results suggest a good penetration of foscarnet into the retinal and brain tissues, reaching higher concentrations than those estimated from vitreous humor and CSF levels.
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http://dx.doi.org/10.1128/AAC.44.3.756-759.2000 | DOI Listing |
Front Immunol
January 2025
Microbiology and Cell Science, Institute of Food and Agricultural Science, University of Florida, Gainesville, FL, United States.
Introduction: Recurrent uveitis (RU), an autoimmune disease, is a leading cause of ocular detriment in humans and horses. Equine and human RU share many similarities including spontaneous disease and aberrant cytokine signaling. Reduced levels of SOCS1, a critical regulator of cytokine signaling, is associated with several autoimmune diseases.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Ophthalmology, Penn State University, Hershey, PA 17033, USA.
Extracellular vesicles (EVs) are lipid bilayer particles released by virtually all cells, with prominent roles in both physiological and pathological processes. The size, number, and molecular composition of released EVs correlate to the cells of origin, modulated by the cell's environment and pathologic state. The proteins, DNA, RNA, and protein cargo carried by EVs are protected by degradation, with a prominent role in targeted intercellular signaling.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Shimotsuke-shi 329-0498, Tochigi, Japan.
Aflibercept and brolucizumab, two anti-VEGF agents used as intravitreal injections in ophthalmology, differ significantly in molecular weight (aflibercept-115 kDa and brolucizumab-26 kDa). Using aqueous humor samples collected after drug administration, we measured and performed a comparative analysis of pharmacokinetics and half-lives of these drugs in the human eye. Since the quantification of monoclonal antibodies (mAbs) using antigen-antibody reactions, such as ELISA, is influenced by endogenous ligands or anti-drug antibodies, we employed nano-surface and molecular-orientation limited proteolysis (nSMOL), combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS), for accurate measurements.
View Article and Find Full Text PDFBiomedicines
January 2025
Department of Histology and Embryology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-092 Bydgoszcz, Poland.
Under normal conditions, potassium is predominantly found within cells. The concentration gradient of sodium and potassium ions between intracellular and extracellular spaces enables signal transmission through membrane depolarization. The disruption of this transcellular process leads to elevated potassium ion levels in the extracellular space, and thus in the blood, a condition known as hyperkalemia.
View Article and Find Full Text PDFOphthalmol Sci
November 2024
A2-Ai, Ann Arbor, Michigan.
Objective: To develop a population pharmacokinetic (PK) model to characterize serum pegcetacoplan concentration-time data after intravitreal administration in patients with geographic atrophy (GA) or neovascular age-related macular degeneration (nAMD).
Design: Pharmacokinetic modeling.
Participants: Two hundred sixty-one patients with GA or nAMD enrolled in 4 clinical studies of pegcetacoplan.
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