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Intravitreal Administration of Avacincaptad Pegol in a Nonhuman Primate Model of Dry Age-Related Macular Degeneration.
Pharmacol Res Perspect
February 2025
Hamamatsu Pharma Research, Inc., Hamamatsu, Shizuoka, Japan.
The lack of effective treatments for dry age-related macular degeneration (AMD) is in part due to a lack of a preclinical animal model that recapitulates features of the clinical state including macular retinal pigment epithelium (RPE) degeneration, also known as geographic atrophy (GA). A nonhuman primate model of GA was developed and its responsiveness to an approved treatment, avacincaptad pegol (ACP), a complement C5 inhibitor, was evaluated. Intravitreal (ivt) administration of sodium iodate (SI) into one eye of male Macaca fascicularis leads to retinal areas (mm) of hyper- or hypo-autofluorescence.
View Article and Find Full Text PDFImpact of obesity and roux-en-Y gastric bypass on the pharmacokinetics of (R)- and (S)-omeprazole and intragastric pH.
CPT Pharmacometrics Syst Pharmacol
September 2024
Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, Florida, USA.
This study employed physiologically-based pharmacokinetic-pharmacodynamics (PBPK/PD) modeling to predict the effect of obesity and gastric bypass surgery on the pharmacokinetics and intragastric pH following omeprazole treatment. The simulated plasma concentrations closely matched the observed data from non-obese, morbidly obese, and post-gastric bypass populations. Obesity significantly reduces CYP3A4 and CYP2C19 activities, as reflected by the metabolic ratio [omeprazole sulphone]/[omeprazole] and [5-hydroxy-omeprazole]/[omeprazole].
View Article and Find Full Text PDFInhalable Textile Microplastic Fibers Impair Airway Epithelial Differentiation.
Am J Respir Crit Care Med
February 2024
Department of Molecular Pharmacology.
Microplastics are a pressing global concern, and inhalation of microplastic fibers has been associated with interstitial and bronchial inflammation in flock workers. However, how microplastic fibers affect the lungs is unknown. Our aim was to assess the effects of 12 × 31 μm nylon 6,6 (nylon) and 15 × 52 μm polyethylene terephthalate (polyester) textile microplastic fibers on lung epithelial growth and differentiation.
View Article and Find Full Text PDFDeuterium Magnetic Resonance Spectroscopy Quantifies Tumor Fraction in a Mouse Model of a Mixed Radiation Necrosis / GL261-Glioblastoma Lesion.
Mol Imaging Biol
February 2024
Department of Radiology, Biomedical MR Center, Washington University, 660 South Euclid Avenue, MO 63110, St. Louis, MO, Mail Stop Code: MSC 8227-0082-02, USA.
Purpose: Distinguishing recurrent brain tumor from treatment effects, including late time-to-onset radiation necrosis (RN), presents an on-going challenge in post-treatment imaging of neuro-oncology patients. Experiments were performed in a novel mouse model that recapitulates the relevant clinical histologic features of recurrent glioblastoma growing in a RN environment, the mixed tumor/RN model. The goal of this work was to apply single-voxel deuterium (H) magnetic resonance spectroscopy (MRS), in concert with administration of deuterated glucose, to determine if the metabolic signature of aerobic glycolysis (Warburg effect: glucose → lactate in the presence of O), a distinguishing characteristic of proliferating tumor, provides a quantitative readout of the tumor fraction (percent) in a mixed tumor/RN lesion.
View Article and Find Full Text PDFCineECG analysis provides new insights into Familial ST-segment Depression Syndrome.
Europace
May 2023
Department of Cardiology, The Heart Centre, Copenhagen University Hospital-Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Aims: Familial ST-segment Depression Syndrome (Fam-STD) is a novel inherited cardiac disease associated with arrhythmias and sudden cardiac death. This study aimed at investigating the cardiac activation pathway in patients with Fam-STD, modelling the electrocardiogram (ECG) phenotype, and performing in-depth ST-segment analyses.
Methods And Results: CineECG analysis of patients with Fam-STD and age- and sex-matched controls.
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