التفاصيل البيبلوغرافية
| العنوان: |
A novel composition of endogenous metabolic modulators improves red blood cell properties in sickle cell disease |
| المؤلفون: |
van Dijk, Myrthe J, Traets, Marissa J M, van Oirschot, Brigitte A, Ruiter, Titine J J, de Wilde, Jonathan R A, Bos, Jennifer, van Solinge, Wouter W, Koziel, Margaret J, Jans, Judith J M, Wani, Revati, van Beers, Eduard J, van Wijk, Richard, Rab, Minke A E |
| المساهمون: |
CDL Rode cel, Unit Opleiding Aios, Cancer, Genetica Sectie Metabole Diagnostiek, CDL Research analisten, Centraal Diagnostisch Laboratorium, Brain, Child Health, Poli Van Creveldkliniek Medisch, CDL Cluster Speciële Diagnostiek, Circulatory Health |
| سنة النشر: |
2024 |
| مصطلحات موضوعية: |
amino acids, anemia, metabolism, red blood cell, sickle cell disease, Journal Article |
| الوصف: |
The most common forms of sickle cell disease (SCD) are sickle cell anemia (SCA; HbSS) and HbSC disease. In both, especially the more dense, dehydrated and adherent red blood cells (RBCs) with reduced deformability are prone to hemolysis and sickling, and thereby vaso-occlusion. Based on plasma amino acid profiling in SCD, a composition of 10 amino acids and derivatives (RCitNacQCarLKHVS; Axcella Therapeutics, USA), referred to as endogenous metabolic modulators (EMMs), was designed to target RBC metabolism. The effects of ex vivo treatment with the EMM composition on different RBC properties were studied in SCD ( n = 9 SCA, n = 5 HbSC disease). Dose-dependent improvements were observed in RBC hydration assessed by hemocytometry (MCV, MCHC, dense RBCs) and osmotic gradient ektacytometry (Ohyper). Median (interquartile range [IQR]) increase in Ohyper compared to vehicle was 4.9% (4.0%-5.5%), 7.5% (6.9%-9.4%), and 12.8% (11.5%-14.0%) with increasing 20×, 40×, and 80X concentrations, respectively (all p < 0.0001). RBC deformability (EImax using oxygen gradient ektacytometry) increased by 8.1% (2.2%-12.1%; p = 0.0012), 9.6% (2.9%-15.1%; p = 0.0013), and 13.3% (5.7%-25.5%; p = 0.0007), respectively. Besides, RBC adhesion to subendothelial laminin decreased by 43% (6%-68%; p = 0.4324), 58% (48%-72%; p = 0.0185), and 71% (49%-82%; p = 0.0016), respectively. Together, these results provide a rationale for further studies with the EMM composition targeting multiple RBC properties in SCD. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| تدمد: |
2688-6146 |
| العلاقة: |
https://dspace.library.uu.nl/handle/1874/451384Test |
| الإتاحة: |
https://dspace.library.uu.nl/handle/1874/451384Test |
| حقوق: |
info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: |
edsbas.84E7743F |
| قاعدة البيانات: |
BASE |
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