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Ex-vivo rbc

Hala Mahmoud Helal, Sana Mohamed Mortada, Marwa Ahmed Sallam
Paliperidone (PPD) is the most recent second-generation atypical antipsychotic approved for the treatment of schizophrenia. An immediate release dose causes extrapyramidal side effects. In this work, a novel nanolipomer carrier system for PPD with enhanced intestinal permeability and sustained release properties has been developed and optimized. PPD was successfully encapsulated into a lipomer consisting of a specific combination of biocompatible materials including poly-ε-caprolactone as a polymeric core, Lipoid S75, and Gelucire® 50/13 as a lipid shell and polyvinyl alcohol as a stabilizing agent...
December 2, 2016: AAPS PharmSciTech
Sabine Kupzig, Stephen F Parsons, Elinor Curnow, David J Anstee, Allison Blair
The generation of cultured red blood cells from stem cell sources may fill an unmet clinical need for transfusion dependent patients, particularly in countries that lack a sufficient and safe blood supply. Cultured red blood cells were generated from human CD34+ cells from adult peripheral blood or cord blood by ex vivo expansion and a comprehensive in vivo survival comparison with standard red cell concentrates was undertaken. Significant amplification (>105 fold) was achieved using CD34+ cells from both cord blood and peripheral blood, generating high yields of enucleated cultured red blood cells...
December 1, 2016: Haematologica
Saba Parween, Elena Kostromina, Christoffer Nord, Maria Eriksson, Per Lindström, Ulf Ahlgren
The leptin deficient ob/ob mouse is a widely used model for studies on initial aspects of metabolic disturbances leading to type 2 diabetes, including insulin resistance and obesity. Although it is generally accepted that ob/ob mice display a dramatic increase in β-cell mass to compensate for increased insulin demand, the spatial and quantitative dynamics of β-cell mass distribution in this model has not been assessed by modern optical 3D imaging techniques. We applied optical projection tomography and ultramicroscopy imaging to extract information about individual islet β-cell volumes throughout the volume of ob/ob pancreas between 4 and 52 weeks of age...
October 7, 2016: Scientific Reports
S Begue, P Morel, R Djoudi
If technological innovations are not enough alone to improve blood safety, their contributions for several decades in blood transfusion are major. The improvement of blood donation (new apheresis devices, RFID) or blood components (additive solutions, pathogen reduction technology, automated processing of platelets concentrates) or manufacturing process of these products (by automated processing of whole blood), all these steps where technological innovations were implemented, lead us to better traceability, more efficient processes, quality improvement of blood products and therefore increased blood safety for blood donors and patients...
September 5, 2016: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
Zhen Bian, Lei Shi, Ya-Lan Guo, Zhiyuan Lv, Cong Tang, Shuo Niu, Alexandra Tremblay, Mahathi Venkataramani, Courtney Culpepper, Limin Li, Zhen Zhou, Ahmed Mansour, Yongliang Zhang, Andrew Gewirtz, Koby Kidder, Ke Zen, Yuan Liu
Rapid clearance of adoptively transferred Cd47-null (Cd47(-/-)) cells in congeneic WT mice suggests a critical self-recognition mechanism, in which CD47 is the ubiquitous marker of self, and its interaction with macrophage signal regulatory protein α (SIRPα) triggers inhibitory signaling through SIRPα cytoplasmic immunoreceptor tyrosine-based inhibition motifs and tyrosine phosphatase SHP-1/2. However, instead of displaying self-destruction phenotypes, Cd47(-/-) mice manifest no, or only mild, macrophage phagocytosis toward self-cells except under the nonobese diabetic background...
September 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
Diane D'Allard, Johnson Liu
Diamond Blackfan anemia (DBA) is a well known inherited bone marrow failure syndrome mostly caused by mutations in ribosomal protein (RP) genes but also rarely in the hematopoietic transcription factor gene, <i>GATA1</i>, or <i>TSR2</i>, a ribosomal protein (Rps26) chaperone gene. About 25% of patients have heterozygous mutations in the <i>RPS19</i> gene, which leads to haploinsufficiency of Rps19 protein in most cases. However, some <i>RPS19</i> missense mutations appear to act in a dominant negative fashion...
August 22, 2016: Human Gene Therapy
Jerard Seghatchian, Jean Amiral
Blood cells generate heterogeneous populations of vesicles that are delivered, as small-specialized packages of highly active cell fragments in blood circulation, having almost similar functional activities, as the mother cells. These so called extracellular vesicles are the essential part of an energy-dependent natural apoptotic process; hence their beneficial and harmful biological functions cannot be ignored. Evidence is accumulating, that cellular derived vesicles, originate from all viable cells including: megakaryocytes, platelets, red blood cells, white blood cells and endothelial cells, the highest in proportions from platelets...
August 2016: Transfusion and Apheresis Science
Andrea Hubeny, Markus Keiser, Stefan Oswald, Gabriele Jedlitschky, Heyo K Kroemer, Werner Siegmund, Markus Grube
Important antimalarial drugs, including quinolines, act against blood schizonts by interfering with hemoglobin metabolism. To reach their site of action, these compounds have to cross the plasma membrane of red blood cells (RBCs). Organic cation transporters (OCTs) and organic anion transporting polypeptides (OATPs) are important uptake transporters and interesting candidates for local drug transport. We therefore studied their interaction with antimalarial compounds (quinine, chloroquine, mefloquine, pyrimethamine, artemisinin, and artesunate) and characterized the expression of OATP1A2 and OATP2B1 in RBCs...
October 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Helen Shinru Wei, Hongyi Kang, Izad-Yar Daniel Rasheed, Sitong Zhou, Nanhong Lou, Anna Gershteyn, Evan Daniel McConnell, Yixuan Wang, Kristopher Emil Richardson, Andre Francis Palmer, Chris Xu, Jiandi Wan, Maiken Nedergaard
Energy production in the brain depends almost exclusively on oxidative metabolism. Neurons have small energy reserves and require a continuous supply of oxygen (O2). It is therefore not surprising that one of the hallmarks of normal brain function is the tight coupling between cerebral blood flow and neuronal activity. Since capillaries are embedded in the O2-consuming neuropil, we have here examined whether activity-dependent dips in O2 tension drive capillary hyperemia. In vivo analyses showed that transient dips in tissue O2 tension elicit capillary hyperemia...
August 17, 2016: Neuron
Raymond Liang, Saghi Ghaffari
Anaemia or decreased blood haemoglobin is the most common blood disorder often characterized by reduced red blood cell (RBC) numbers. RBCs are produced from differentiation and commitment of haematopoietic stem cells to the erythroid lineage by a process called erythropoiesis. Coordination of erythropoietin receptor signalling with several erythroid transcription factors including GATA1 is essential for this process. A number of additional players that are critical for RBC production have been identified in recent years...
September 2016: British Journal of Haematology
Mainak Chakraborty, Indrajit Karmakar, Sagnik Haldar, Avratanu Das, Asis Bala, Pallab Kanti Haldar
INTRODUCTION: The present study evaluates the antioxidant effect of methanol extract of Hippophae salicifolia (MEHS) bark with special emphasis on its role on oxidative DNA damage in mouse peritoneal macrophages. MATERIAL AND METHODS: In vitro antioxidant activity was estimated by standard antioxidant assays whereas the antioxidant activity concluded the H(+) donating capacity. Mouse erythrocytes' hemolysis and peritoneal macrophages' DNA damage were determined spectrophotometrically...
July 2016: Journal of Pharmacy & Bioallied Sciences
Julie A Reisz, Matthew J Wither, Monika Dzieciatkowska, Travis Nemkov, Aaron Issaian, Tatsuro Yoshida, Andrew J Dunham, Ryan C Hill, Kirk C Hansen, Angelo D'Alessandro
Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) plays a key regulatory function in glucose oxidation by mediating fluxes through glycolysis or the pentose phosphate pathway (PPP) in an oxidative stress-dependent fashion. Previous studies documented metabolic reprogramming in stored red blood cells (RBCs) and oxidation of GAPDH at functional residues upon exposure to pro-oxidants diamide and H2O2 Here we hypothesize that routine storage of erythrocyte concentrates promotes metabolic modulation of stored RBCs by targeting functional thiol residues of GAPDH...
September 22, 2016: Blood
Donna Oksenberg, Kobina Dufu, Mira P Patel, Chihyuan Chuang, Zhe Li, Qing Xu, Abel Silva-Garcia, Chengjing Zhou, Athiwat Hutchaleelaha, Larysa Patskovska, Yury Patskovsky, Steven C Almo, Uma Sinha, Brian W Metcalf, David R Archer
A major driver of the pathophysiology of sickle cell disease (SCD) is polymerization of deoxygenated haemoglobin S (HbS), which leads to sickling and destruction of red blood cells (RBCs) and end-organ damage. Pharmacologically increasing the proportion of oxygenated HbS in RBCs may inhibit polymerization, prevent sickling and provide long term disease modification. We report that GBT440, a small molecule which binds to the N-terminal α chain of Hb, increases HbS affinity for oxygen, delays in vitro HbS polymerization and prevents sickling of RBCs...
October 2016: British Journal of Haematology
Nathalie Chami, Ming-Huei Chen, Andrew J Slater, John D Eicher, Evangelos Evangelou, Salman M Tajuddin, Latisha Love-Gregory, Tim Kacprowski, Ursula M Schick, Akihiro Nomura, Ayush Giri, Samuel Lessard, Jennifer A Brody, Claudia Schurmann, Nathan Pankratz, Lisa R Yanek, Ani Manichaikul, Raha Pazoki, Evelin Mihailov, W David Hill, Laura M Raffield, Amber Burt, Traci M Bartz, Diane M Becker, Lewis C Becker, Eric Boerwinkle, Jette Bork-Jensen, Erwin P Bottinger, Michelle L O'Donoghue, David R Crosslin, Simon de Denus, Marie-Pierre Dubé, Paul Elliott, Gunnar Engström, Michele K Evans, James S Floyd, Myriam Fornage, He Gao, Andreas Greinacher, Vilmundur Gudnason, Torben Hansen, Tamara B Harris, Caroline Hayward, Jussi Hernesniemi, Heather M Highland, Joel N Hirschhorn, Albert Hofman, Marguerite R Irvin, Mika Kähönen, Ethan Lange, Lenore J Launer, Terho Lehtimäki, Jin Li, David C M Liewald, Allan Linneberg, Yongmei Liu, Yingchang Lu, Leo-Pekka Lyytikäinen, Reedik Mägi, Rasika A Mathias, Olle Melander, Andres Metspalu, Nina Mononen, Mike A Nalls, Deborah A Nickerson, Kjell Nikus, Chris J O'Donnell, Marju Orho-Melander, Oluf Pedersen, Astrid Petersmann, Linda Polfus, Bruce M Psaty, Olli T Raitakari, Emma Raitoharju, Melissa Richard, Kenneth M Rice, Fernando Rivadeneira, Jerome I Rotter, Frank Schmidt, Albert Vernon Smith, John M Starr, Kent D Taylor, Alexander Teumer, Betina H Thuesen, Eric S Torstenson, Russell P Tracy, Ioanna Tzoulaki, Neil A Zakai, Caterina Vacchi-Suzzi, Cornelia M van Duijn, Frank J A van Rooij, Mary Cushman, Ian J Deary, Digna R Velez Edwards, Anne-Claire Vergnaud, Lars Wallentin, Dawn M Waterworth, Harvey D White, James G Wilson, Alan B Zonderman, Sekar Kathiresan, Niels Grarup, Tõnu Esko, Ruth J F Loos, Leslie A Lange, Nauder Faraday, Nada A Abumrad, Todd L Edwards, Santhi K Ganesh, Paul L Auer, Andrew D Johnson, Alexander P Reiner, Guillaume Lettre
Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3...
July 7, 2016: American Journal of Human Genetics
William F Jackson
Arterioles in the peripheral microcirculation are exquisitely sensitive to changes in PO2 in their environment: increases in PO2 cause vasoconstriction while decreases in PO2 result in vasodilatation. However, the cell type that senses O2 (the O2 sensor) and the signalling pathway that couples changes in PO2 to changes in arteriolar tone (the mechanism of action) remain unclear. Many (but not all) ex vivo studies of isolated cannulated resistance arteries and large, first-order arterioles support the hypothesis that these vessels are intrinsically sensitive to PO2 with the smooth muscle, endothelial cells, or red blood cells serving as the O2 sensor...
September 15, 2016: Journal of Physiology
S A Hosgood, K Saeb-Parsy, M O Hamed, M L Nicholson
We report the successful transplantation of a pair of human kidneys that were declined for transplantation due to inadequate in situ perfusion but subsequently transplanted after perfusion and assessment using ex vivo normothermic perfusion (EVNP). The kidneys were from a 35-year-old man, a donation after circulatory death donor. Both kidneys were declined by all UK transplant centers. On arrival, the kidneys had significant areas of incomplete clearance of blood from the microcirculation that did not clear after a further attempt to flush them...
November 2016: American Journal of Transplantation
Catarina Duarte, Susana Pinto, Patrícia Napoleão, Ana Catarina Pronto-Laborinho, Maria Amparo Barros, Teresa Freitas, Mamede de Carvalho, Carlota Saldanha
INTRODUCTION: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease of the motor system. It has been hypothesised that red blood cells (RBCs) may be involved in the disease process by the release of damaging molecules. OBJECTIVE: The aim of this ex vivo study is to compare RBCs biochemical and hemorheological parameters between ALS patients and healthy donors to identify novel biomarkers of the ALS disease. METHODS: We included 82 ALS patients and 40 gender age-matched healthy donors...
May 30, 2016: Clinical Hemorheology and Microcirculation
Alessandra Stampella, Sabrina Di Marco, Daniela Pirri, Xavier de la Torre, Francesco Botrè, Francesco Donati
In this work we present the application of a method for the identification of homologous blood transfusions using forensic genetic techniques based on DNA typing. Ex vivo mixtures of human blood samples - either whole blood or red blood cell concentrates - simulating homologous blood transfusions at different percentages of the donor were typed for a panel of 16 highly variable DNA short tandem repeats (STR). Tested samples included also mixtures, which gave false-negative results if assayed by the reference flow cytofluorimetric method, which is based on the recognition of target antigens located on the membrane of the red blood cell...
August 2016: Forensic Science International
Scott L Diamond
The systems analysis of thrombosis seeks to quantitatively predict blood function in a given vascular wall and hemodynamic context. Relevant to both venous and arterial thrombosis, a Blood Systems Biology approach should provide metrics for rate and molecular mechanisms of clot growth, thrombotic risk, pharmacological response, and utility of new therapeutic targets. As a rapidly created multicellular aggregate with a polymerized fibrin matrix, blood clots result from hundreds of unique reactions within and around platelets propagating in space and time under hemodynamic conditions...
April 29, 2016: Circulation Research
Michel Prudent, Frédéric Stauber, Alexis Rapin, Sonia Hallen, Nicole Pham, Mélanie Abonnenc, Laure Marvin, Bertrand Rochat, Jean-Daniel Tissot, Niels Lion
To date, the development of bioreactors for the study of red blood cells (RBCs, daily transfused in the case of disease or hemorrhage) has focused on hematopoietic stem cells. Despite the fact that mature RBCs are enucleated and do not expand, they possess complex cellular and metabolic pathways, as well as post-translation modification signaling and gas-exchange regulation. In order to dynamically study the behavior of RBCs and their signaling pathways under various conditions, a small-scale perfusion bioreactor has been developed...
2016: Frontiers in Molecular Biosciences
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