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TARGETING LUNG HEME IRON BY AEROSOL HEMOPEXIN ADMINSTRATION IN SICKLE CELL DISEASE PULMONARY HYPERTENSION.
Free Radic Biol Med
January 2025
University of Colorado, Anschutz Medical Campus School of Medicine| Translational research laboratory of Red Blood Cell Diseases and Hypoxia related illnesses| Cardiovascular Pulmonary Research (CVP) group, Pediatrics. Electronic address:
Lung tissue from human patients and murine models of sickle cell disease pulmonary hypertension (SCD-PH) show perivascular regions with excessive iron accumulation. The iron accumulation arises from chronic hemolysis and extravasation of hemoglobin (Hb) into the lung adventitial spaces, where it is linked to nitric oxide depletion, oxidative stress, inflammation, and tissue hypoxia, which collectively drive SCD-PH. Here, we tested the hypothesis that intrapulmonary delivery of hemopexin (Hpx) to the deep lung is effective at scavenging heme-iron and attenuating the progression of SCD-PH.
View Article and Find Full Text PDFIn Vitro, In Vivo, Ex Vivo Characterisation of Dihydroimidazotriazinones and Their Thermal Decomposition Course Studied by Coupled and Simultaneous Thermal Analysis Methods.
Int J Mol Sci
January 2025
Laboratory of Bioorganic Compounds Synthesis and Analysis, Medical University of Lublin, 4A Chodźki Street, 20-093 Lublin, Poland.
The biological and thermal properties of a class of synthetic dihydroimidazotriazinones were disclosed in this article for the first time. Molecules --as potential innovative antimetabolites mimicking bicyclic aza-analogues of isocytosine-were evaluated for their in vitro anticancer activity. Moreover, in vivo, in vitro, and ex vivo toxicity profiles of all the compounds were established in zebrafish, non-tumour cell, and erythrocyte models, respectively.
View Article and Find Full Text PDFElevated uric acid levels, mortality and cognitive impairment in children with severe malaria.
Nat Med
January 2025
Ryan White Center for Pediatric Infectious Diseases and Global Health, Indiana University School of Medicine, Indianapolis, IN, USA.
We investigated the role of uric acid in the pathogenesis of severe malaria (SM) in two independent cohorts of children with SM. Hyperuricemia (blood uric acid ≥ 7 mg dl) was present in 25% of children with SM and was associated with increased in-hospital mortality and postdischarge mortality in both cohorts. Increased blood uric acid levels were also associated with worse scores in overall cognition in children with SM < 5 years old in both cohorts.
View Article and Find Full Text PDFRavulizumab demonstrates long-term efficacy, safety and favorable patient survival in patients with paroxysmal nocturnal hemoglobinuria.
Ann Hematol
January 2025
Division of Hematology-Oncology, Hanyang University Seoul Hospital, Seoul, Republic of Korea.
Ravulizumab is a second-generation complement component 5 (C5) inhibitor (C5i) approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) following positive results from two pivotal trials in patients with PNH originally naive to C5i treatment and eculizumab-experienced patients with PNH. In both trials, after the 26week primary evaluation period, all patients received ravulizumab for up to 6 years. To report ravulizumab treatment outcomes in patients with PNH originally naive to C5i treatment and eculizumab-experienced patients with PNH treated for up to 6 years.
View Article and Find Full Text PDFDevelopment of an easy non-destructive particle isolation protocol for quality control of red blood cell concentrates.
J Extracell Biol
January 2025
Cell Biology Unit & Platform for Imaging Cells and Tissues, de Duve Institute UCLouvain Brussels Belgium.
The extracellular vesicle release in red blood cell concentrates reflects progressive accumulation of storage lesions and could represent a new measure to be implemented routinely in blood centres in addition to haemolysis. Nevertheless, there is currently no standardized isolation protocol. In a previous publication, we developed a reproducible ultracentrifugation-based protocol (20,000 × protocol) that allows to classify red blood cell concentrates into three cohorts according to their vesiculation level.
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