A recent unexpected finding of inhibited platelet aggregation in response to a single (1.64 mmol/l) dose of arachidonic acid (AA), during the relapse of childhood nephrosis, prompted us to assess aggregation in response to multiple doses of AA: 1.64,0.82,0.41,0.20 mmol/l, in two groups of children, in the relapse (n = 34) or remission (n=41) phase of nephrotic syndrome. During relapse: the highest dose of AA (1.64 mmol/l) evoked reversible and inhibited aggregation in 91% of patients. However, at the lower doses there were enhanced responses as measured by both maximum aggregation (%) and slopes of the aggregation curves. In contrast, during remission, irreversible aggregation was obtained at the highest AA dose, while at the lowest two doses (0.41 and 0.20 mmol/l), no aggregation responses were obtained in 4 (9%) and 7 (17%) patients respectively; in those who responded there was a long lag phase. Healthy controls (n = 21) exhibited their highest responses to 1.64 and 0.82 mmol/l AA and at the lowest AA doses (0.41 and 0.20 mmol/l), a total absence of responses was noted in 40% and 71% of samples respectively. We conclude that during relapse platelet sensitivity, as shown by irreversible aggregation in response to multiple AA doses, shifts towards the lower doses, when compared with healthy controls; while during remission responses fall in-between the relapse and control groups, indicating the maintenance of platelet sensitivity during this phase of nephrosis.
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http://dx.doi.org/10.3109/09537109509078446 | DOI Listing |
Geroscience
January 2025
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Cellular senescence is a phenotypic state that contributes to the progression of age-related disease through secretion of pro-inflammatory factors known as the senescence-associated secretory phenotype (SASP). Understanding the process by which healthy cells become senescent and develop SASP factors is critical for improving the identification of senescent cells and, ultimately, understanding tissue dysfunction. Here, we reveal how the duration of cellular stress modulates the SASP in distinct subpopulations of senescent cells.
View Article and Find Full Text PDFEur J Pharmacol
January 2025
Department of Drug and Health Sciences, Pharmacology and Toxicology Section, University of Catania, Italy; Oasi Research Institute-IRCCS, 94018 Troina, Italy. Electronic address:
Background: Adamantane derivatives, such as memantine (Mem) and amantadine (Ada), have distinct mechanisms and therapeutic applications. Ada is primarily utilized as an antiviral and anti-Parkinson drug without significant pro-cognitive effects, Mem is effective in various clinical conditions characterized by cognitive deficits, including Alzheimer's disease. Recent evidence highlights a neuroprotective role for Aβ monomers, suggesting that preventing their aggregation into toxic oligomers could be a promising therapeutic strategy.
View Article and Find Full Text PDFActa Biomater
January 2025
Department of radiology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214122, China. Electronic address:
Nanohybrids combining phenylboronic acid-modified carbon dots (PCDs) and proteinase K have been engineered for addressing the formidable challenges of antimicrobial photodynamic therapy (aPDT) against bacterial biofilm infections, overcoming biofilm barrier obstruction, the limited diffusion of reactive oxygen species (ROS), and the inadequate ROS generation of traditional photosensitizers. PCDs are formulated for superior water solubility and robust singlet oxygen (O) production, mitigating issues related to dispersion and aggregation-induced quenching typical of conventional photosensitizers. The conjugation of phenylboronic acid to CDs not only enhanced O generation through increased electron-hole separation but also imparted strong bacterial binding capabilities to the PCDs, enabling broad-spectrum sterilization by maximizing the ROS-mediated bacterial destruction.
View Article and Find Full Text PDFDrug Metab Pharmacokinet
January 2025
Department of Clinical Regenerative Medicine, Fujita Medical Innovation Center Tokyo, Fujita Health University, Tokyo, Japan; Department of Cardiology, Keio University School of Medicine, Tokyo, Japan. Electronic address:
Recently human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have become an attractive platform to evaluate drug responses for cardiotoxicity testing and disease modeling. Moreover, three-dimensional (3D) cardiac models, such as engineered heart tissues (EHTs) developed by bioengineering approaches, and cardiac spheroids (CSs) formed by spherical aggregation of hPSC-CMs, have been established as useful tools for drug discovery and transplantation. These 3D models overcome many of the shortcomings of conventional 2D hPSC-CMs, such as immaturity of the cells.
View Article and Find Full Text PDFJ Clin Invest
January 2025
Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, China.
Background: B7-H3 or CD276 is notably overexpressed in various malignant tumor cells in humans, with extremely high expression rates. The development of a radiotracer that targets B7-H3 may provide a universal tumor-specific imaging agent and allow the noninvasive assessment of the whole-body distribution of B7-H3-expressing lesions.
Methods: We enhanced and optimized the structure of an affibody (ABY) that targets B7-H3 to create the radiolabeled radiotracer [68Ga]Ga-B7H3-BCH, and then, we conducted both foundational experiments and clinical translational studies.
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