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PBPK modeling of recombinant factor IX Fc fusion protein (rFIXFc) and rFIX to characterize the binding to type 4 collagen in the extravascular space.
CPT Pharmacometrics Syst Pharmacol
October 2024
Department of Hospital Pharmacy-Clinical Pharmacology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.
Article Synopsis
- Patients with hemophilia B receive factor IX concentrates to prevent bleeding, and new extended half-life (EHL) options allow for less frequent dosing compared to standard treatments.
- The recombinant FIX-Fc fusion protein (rFIXFc) is highlighted for its rapid distribution, potentially due to its binding to type IV collagen in the body, which may help prevent bleeding even when FIX activity is not measurable in plasma.
- A physiologically based pharmacokinetic (PBPK) model accurately predicts how rFIXFc behaves in the body, showing significantly higher concentrations of the drug in the extravascular space compared to plasma, indicating its crucial role in achieving effective bleeding control after treatment.
Mechanical confinement prevents ectopic platelet release.
Proc Natl Acad Sci U S A
September 2024
University of Strasbourg, INSERM, Etablissement Français du Sang (EFS) Grand-Est, UMR_S1255 Biologie et Pharmacologie des Plaquettes Sanguines (BPPS), FMTS, Strasbourg F-67065, France.
Blood platelets are produced by megakaryocytes (MKs), their parent cells, which are in the bone marrow. Once mature, MK pierces through the sinusoid vessel, and the initial protrusion further elongates as proplatelet or buds to release platelets. The mechanisms controlling the decision to initiate proplatelet and platelet formation are unknown.
View Article and Find Full Text PDFNon-immune hydrops fetalis is associated with bi-allelic pathogenic variants in the MYB Binding Protein 1a (MYBBP1A) gene.
Clin Genet
December 2024
CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain.
Non-immune hydrops fetalis (NIHF) is a rare entity characterized by excessive accumulation of fluid within the fetal extravascular compartments and body cavities. Here we present two intrauterine fetal demises with NIHF presenting with oligohydramnios, cystic hygroma, pleural effusion, and generalized hydrops with predominance of subcutaneous edema. The fetuses also presented with ascites, severe and precocious IUGR and skeletal anomalies.
View Article and Find Full Text PDFRecombinant human thrombopoietin in alleviating endothelial cell injury in sepsis.
J Intensive Med
July 2024
Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background: To evaluate the effect of recombinant human thrombopoietin (rhTPO) on clinical prognosis by exploring changes in endothelial cell injury markers and inflammatory factors in patients with sepsis after treatment with rhTPO.
Methods: This retrospective observational study involved patients with sepsis (diagnosed according to Sepsis 3.0) admitted to Shanghai General Hospital intensive care unit from January 1, 2019 to December 31, 2022.
Mechanisms of whole body, respiratory, acid-base buffering: a first computer-model test of three physicochemical, acid-base theories.
J Appl Physiol (1985)
June 2024
Department of Pharmacology, Physiology and Neuroscience, University of South Carolina, Columbia, South Carolina, United States.
Acid-base disorders are currently analyzed and treated using a bicarbonate-centered approach derived from blood studies prior to the advent of digital computers, which could solve computer models capable of quantifying the complex physicochemical nature governing distribution of water and ions between fluid compartments. An alternative is the Stewart approach, which can predict the pH of a simple mixture of ions and electrically charged proteins; hence, the role of extravascular fluids has been largely ignored. The present study uses a new, comprehensive computer model of four major fluid compartments, based on a recent blood model, which included ion binding to proteins, electroneutrality constraints, and other essential physicochemical laws.
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