Cell-free hemoglobin solutions with high oxygen affinity might be beneficial for selectively delivering oxygen to ischemic tissue. A recombinant hybrid hemoglobin molecule was designed using the human alpha-subunit and the bovine beta-subunit, with placement of surface cysteines to permit disulfide bond polymerization of the tetramers. The resulting protein generated from an Escherichia coli expression system had a molecular mass >1 MDa, a P50 of approximately 3 Torr, and a cooperativity of n = 1.0. Anesthetized mice were transfused during 2-h occlusion of the middle cerebral artery. Compared with transfusion with 5% albumin, cerebral infarct volume was reduced by 41% with transfusion of a 3% solution of the high oxygen-affinity hemoglobin polymer and by 50% with transfusion of a 6% solution of the polymer. Transfusion of a 6% solution of a 500-kDa polymer possessing a P50 of 17 Torr and a cooperativity of n = 2.0 resulted in a 66% reduction of infarct volume. These results indicate that cell-free Hb polymers with P50 values much lower than that of red blood cell hemoglobin are highly capable of salvaging ischemic brain. The assumption that the P50 of blood substitutes should be similar to that of blood might not be warranted when used during ischemic conditions.
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http://dx.doi.org/10.1152/japplphysiol.01374.2005 | DOI Listing |
Exp Hematol Oncol
January 2025
Jiangsu Provincial Key Laboratory of Critical Care Medicine, Advanced Institute for Life and Health, Center of Clinical Laboratory Medicine, Department of Pharmacy, School of Medicine, Zhongda Hospital, Southeast University, Nanjing, 210009, China.
Transfusion safety and blood typing continue to present significant challenges in clinical practice, including risks of incorrect blood transfusions and blood shortages. One promising solution is the enzymatic conversion of all red blood cell (RBC) types into universal O-type RBCs. However, the major obstacle to this strategy is the relatively low catalytic efficiency of the enzymes involved.
View Article and Find Full Text PDFJCO Precis Oncol
January 2025
Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA.
Purpose: Fibroblast growth factor receptor 2 isoform IIIb (FGFR2b) protein overexpression is an emerging biomarker in gastric cancer and gastroesophageal junction cancer (GC). We assessed FGFR2b protein overexpression prevalence in nearly 3,800 tumor samples as part of the prescreening process for a global phase III study in patients with newly diagnosed advanced or metastatic GC.
Methods: As of June 28, 2024, 3,782 tumor samples from prescreened patients from 37 countries for the phase III FORTITUDE-101 trial (ClinicalTrials.
Sci Rep
January 2025
Graduate Program in Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathumthani, 12120, Thailand.
Serological typing of MNS polymorphic antigens - M, N, S and s - remains a fundamental technique in transfusion medicine and prenatal care, providing essential information for matching blood donors and recipients and managing haemolytic disease. Although this method is well proven and routinely used, it is not a comprehensive solution, as it has several weaknesses. Alternatively, multiplex polymerase chain reaction (PCR) is a commonly used genotyping tool due to its potency and ability to amplify several DNA targets simultaneously in a single reaction.
View Article and Find Full Text PDFJ Bone Joint Surg Am
January 2025
National Cancer Institute, Cairo University, Giza, Egypt.
Background: Limb-salvage surgery for malignant bone tumors can be associated with considerable perioperative blood loss. The aim of this randomized controlled trial was to assess the safety and efficacy of the intraoperative infusion of tranexamic acid (TXA) in children and adolescents undergoing limb-salvage surgery.
Methods: All participants were <18 years of age at the time of surgery and diagnosed with a malignant bone tumor of the femur that was treated with resection and reconstruction with a megaprosthesis.
J Trauma Acute Care Surg
January 2025
From the Division of Acute Care Surgery, Department of Surgery (E.R.M., T.B.M., C.M.W., H.S., R.H., C.D.B.), University of Nebraska Medical Center, Omaha, Nebraska; Department of Surgery (H.B.M.), AdventHealth Porter; Department of Surgery (E.E.M., J.G.C.), Ernest E Moore Shock Trauma Center at Denver Health, Denver; Department of Surgery (E.E.M.), University of Colorado Anschutz Medical Campus, Aurora, Colorado; Hunter College (I.M.B.), New York, New York; Sauaia Statistical Solutions, LLC (A.S.), Denver, Colorado; and Department of Cellular and Integrative Physiology (F.I.G., C.D.B.), University of Nebraska Medical Center, Omaha, Nebraska.
Background: Tissue-plasminogen activator-challenged thromboelastography (tPA-TEG) predicts massive transfusion and mortality better than conventional rapid thromboelastography (rTEG), with little concordance between their lysis values (LY30). We hypothesized that the main fibrinolytic inhibitors plasminogen activator inhibitor-1 (PAI-1) and α-2 antiplasmin (A2AP), as well as markers of fibrinolytic activation (plasmin-antiplasmin [PAP], tPA-PAI-1 complex, tPA activity), would correlate more strongly with tPA-TEG versus rTEG LY30 and may explain the recent findings of four distinct fibrinolytic phenotypes in trauma based on these two TEG methodologies.
Methods: Adult trauma patients (n = 56) had tPA-TEG, rTEG, and plasma obtained on arrival to the emergency department with institutional review board approval.
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