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1.
Transfusion ; 61 Suppl 1: S223-S233, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269457

RESUMO

BACKGROUND: Parachute airdrop offers a rapid transfusion supply option for humanitarian aid and military support. However, its impact on longer-term RBC survival is undocumented. This study aimed to determine post-drop quality of RBCs in concentrates (RCC), and both RBCs and plasma in whole blood (WB) during subsequent storage. STUDY DESIGN AND METHODS: Twenty-two units of leucodepleted RCC in saline, adenine, glucose, mannitol (SAGM) and 22 units of nonclinical issue WB were randomly allocated for air transportation, parachute drop, and subsequent storage (parachute), or simply storage under identical conventional conditions (4 ± 2°C) (control). All blood products were 6-8 days post-donation. Parachute units were packed into Credo Cubes, (Series 4, 16 L) inside a PeliCase (Peli 0350) and rigged as parachute delivery packs. Packs underwent a 4-h tactical flight (C130 aircraft), then parachuted from 250 to 400 ft before ground recovery. The units were sampled aseptically before and after airdrop at weekly intervals. A range of assays quantified the RBC storage lesion and coagulation parameters. RESULTS: Blood units were maintained at 2-6°C and recovered intact after recorded ground impacts of 341-1038 m s-2 . All units showed a classical RBC storage lesion and increased RBC microparticles during 42 days of storage. Fibrinogen and clotting factors decreased in WB during storage. Nevertheless, no significant difference was observed between Control and Parachute groups. Air transportation and parachute delivery onto land did not adversely affect, or shorten, the shelf life of fresh RBCs or WB. DISCUSSION: Appropriately packaged aerial delivery by parachute can be successfully used for blood supply.


Assuntos
Transfusão de Sangue , Eritrócitos/citologia , Plasma , Transportes , Preservação de Sangue , Humanos , Plasma/química , Indicadores de Qualidade em Assistência à Saúde
2.
Transfusion ; 61 Suppl 1: S243-S251, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269443

RESUMO

BACKGROUND: In traumatic bleeding, transfusion practice has shifted toward higher doses of platelets and plasma transfusion. The aim of this systematic review was to investigate whether a higher platelet-to-red blood cell (RBC) transfusion ratio improves mortality without worsening organ failure when compared with a lower ratio of platelet-to-RBC. METHODS: Pubmed, Medline, and Embase were screened for randomized controlled trials (RCTs) in bleeding trauma patients (age ≥16 years) receiving platelet transfusion between 1946 until October 2020. High platelet:RBC ratio was defined as being the highest ratio within an included study. Primary outcome was 24 hour mortality. Secondary outcomes were 30-day mortality, thromboembolic events, organ failure, and correction of coagulopathy. RESULTS: In total five RCTs (n = 1757 patients) were included. A high platelet:RBC compared with a low platelet:RBC ratio significantly improved 24 hour mortality (odds ratio [OR] 0.69 [0.53-0.89]) and 30- day mortality (OR 0.78 [0.63-0.98]). There was no difference between platelet:RBC ratio groups in thromboembolic events and organ failure. Correction of coagulopathy was reported in five studies, in which platelet dose had no impact on trauma-induced coagulopathy. CONCLUSIONS: In traumatic bleeding, a high platelet:RBC improves mortality as compared to low platelet:RBC ratio. The high platelet:RBC ratio does not influence thromboembolic or organ failure event rates.


Assuntos
Contagem de Eritrócitos , Hemorragia/sangue , Contagem de Plaquetas , Ferimentos e Lesões/sangue , Plaquetas/citologia , Eritrócitos/citologia , Hemorragia/mortalidade , Humanos , Ferimentos e Lesões/mortalidade
3.
Immunity ; 54(7): 1433-1446.e5, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34062116

RESUMO

The extra-embryonic yolk sac contains the first definitive multipotent hematopoietic cells, denominated erythromyeloid progenitors. They originate in situ prior to the emergence of hematopoietic stem cells and give rise to erythroid, monocytes, granulocytes, mast cells and macrophages, the latter in a Myb transcription factor-independent manner. We uncovered here the heterogeneity of yolk sac erythromyeloid progenitors, at the single cell level, and discriminated multipotent from committed progenitors, prior to fetal liver colonization. We identified two temporally distinct megakaryocyte differentiation pathways. The first occurs in the yolk sac, bypasses intermediate bipotent megakaryocyte-erythroid progenitors and, similar to the differentiation of macrophages, is Myb-independent. By contrast, the second originates later, from Myb-dependent bipotent progenitors expressing Csf2rb and colonize the fetal liver, where they give rise to megakaryocytes and to large numbers of erythrocytes. Understanding megakaryocyte development is crucial as they play key functions during vascular development, in particular in separating blood and lymphatic networks.


Assuntos
Diferenciação Celular/fisiologia , Eritrócitos/citologia , Megacariócitos/citologia , Células Mieloides/citologia , Células-Tronco/citologia , Saco Vitelino/citologia , Animais , Linhagem da Célula/fisiologia , Células Cultivadas , Embrião de Mamíferos/citologia , Feminino , Granulócitos/citologia , Hematopoese/fisiologia , Células-Tronco Hematopoéticas/citologia , Macrófagos/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/citologia , Células-Tronco Multipotentes/citologia , Gravidez
4.
Eur Rev Med Pharmacol Sci ; 25(10): 3886-3897, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34109597

RESUMO

OBJECTIVE: Platelets, blood coagulation along with fibrinolysis are greatly involved in the pathophysiology of infectious diseases induced by bacteria, parasites and virus. This phenomenon is not surprising since both the innate immunity and the hemostatic systems are two ancestral mechanisms which closely cooperate favoring host's defense against foreign invaders. However, the excessive response of these systems may be dangerous for the host itself. MATERIALS AND METHODS: We searched and retrieved the articles, using the following electronic database: MedLine and Embase. We limited our search to articles published in English, but no restrictions in terms of article type, publication year, and geography were adopted. RESULTS: The hemostatic phenotype of the infectious diseases is variable depending on the points of attack of the different involved pathogens. Infectious diseases which show a prothrombotic phenotype are bacterial sepsis, SARS-CoV-2 and malaria. However, among the bacterial sepsis, Yersinia Pestis is characterized by a profibrinolytic behavior. On the contrary, the hemorrhagic fevers, due to Dengue and Ebola virus, mainly exploit the activation of fibrinolysis secondary to a huge endothelial damage which can release a large amount of t-PA in the early phase of the diseases. CONCLUSIONS: Blood coagulation and fibrinolysis are greatly activated based on the strategy of the different infectious agents which exploit the excess of response of both systems to achieve the greatest possible virulence.


Assuntos
Coagulação Sanguínea , COVID-19/patologia , Fibrinólise , COVID-19/complicações , COVID-19/virologia , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Células Endoteliais/virologia , Eritrócitos/citologia , Eritrócitos/metabolismo , Eritrócitos/parasitologia , Humanos , Monócitos/citologia , Monócitos/metabolismo , Monócitos/virologia , SARS-CoV-2/isolamento & purificação , Tromboplastina/metabolismo , Vírus/patogenicidade
5.
Molecules ; 26(9)2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-34066773

RESUMO

Besides human red blood cells (RBC), a standard model used in AFM-single cell force spectroscopy (SCFS), little is known about apparent Young's modulus (Ea) or adhesion of animal RBCs displaying distinct cellular features. To close this knowledge gap, we probed chicken, horse, camel, and human fetal RBCs and compared data with human adults serving as a repository for future studies. Additionally, we assessed how measurements are affected under physiological conditions (species-specific temperature in autologous plasma vs. 25 °C in aqueous NaCl solution). In all RBC types, Ea decreased with increasing temperature irrespective of the suspension medium. In mammalian RBCs, adhesion increased with elevated temperatures and scaled with reported membrane sialic acid concentrations. In chicken only adhesion decreased with higher temperature, which we attribute to the lower AE-1 concentration allowing more membrane undulations. Ea decreased further in plasma at every test temperature, and adhesion was completely abolished, pointing to functional cell enlargement by adsorption of plasma components. This halo elevated RBC size by several hundreds of nanometers, blunted the thermal input, and will affect the coupling of RBCs with the flowing plasma. The study evidences the presence of a RBC surface layer and discusses the tremendous effects when RBCs are probed at physiological conditions.


Assuntos
Camelus/sangue , Adesão Celular/fisiologia , Galinhas/sangue , Eritrócitos/citologia , Cavalos/sangue , Microscopia de Força Atômica/métodos , Análise de Célula Única/métodos , Temperatura , Adulto , Animais , Membrana Celular/metabolismo , Humanos
6.
Molecules ; 26(11)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071554

RESUMO

Diabetic dyslipidemia and hyperglycemia contribute to excessive reactive oxygen species (ROS) production, leading to deleterious complications, such as nephropathy, atherosclerosis and cardiac dysfunction, and target major organs in the body. The aim of this study was to investigate the effect of caffeic acid (CA) on mouse weight and survival, serum level of fasting blood glucose (FBG), serum lipid parameters and atherogenic indices, oxidative damage in blood, liver and kidney tissue, pathophysiological changes and their function markers in healthy and alloxan-induced type 1 diabetic mice. Diabetes was induced in mice with a single intravenous injection of alloxan (75 mg kg-1). Two days later, CA (50 mg kg-1) was given intraperitoneally for seven days in diabetic mice. Diabetes affected glucose level, lipid profile, hematological and biochemical parameters, induced DNA damage and apoptotic/necrotic death in whole blood cells, liver and kidney, leading to weight loss and a decreased lifespan. CA treatment of diabetic mice revealed a protective effect on the liver and kidney, hypoglycemic and hypolipidemic properties and high protection against atherogenic outcomes. The obtained results suggest that CA is a safe and potent agent against diabetes that acts as an effective antioxidant in reducing serum glucose, lipid profile and atherogenic indices, leading to increased lifespan in mice.


Assuntos
Ácidos Cafeicos/química , Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Aloxano/química , Animais , Antioxidantes/química , Apoptose , Aterosclerose , Glicemia/análise , Diabetes Mellitus Experimental/metabolismo , Eritrócitos/citologia , Hemólise , Hiperglicemia/tratamento farmacológico , Hipoglicemia/tratamento farmacológico , Peroxidação de Lipídeos , Lipídeos/química , Fígado/efeitos dos fármacos , Masculino , Camundongos , Necrose , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio , Medição de Risco
7.
Commun Biol ; 4(1): 677, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34083702

RESUMO

Immortalized erythroid cell lines are expected to be a promising source of ex vivo manufactured red blood cells (RBCs), however the induction of enucleation in these cell lines is inefficient at present. We utilized an imaging-based high-throughput system to identify chemical compounds that trigger enucleation of human erythroid cell lines. Among >3,300 compounds, we identified multiple histone deacetylase inhibitors (HDACi) inducing enucleated cells from the cell line, although an increase in membrane fragility of enucleated cells was observed. Gene expression profiling revealed that HDACi treatment increased the expression of cytoskeletal genes, while an erythroid-specific cell membrane protein, SPTA1, was significantly down-regulated. Restoration of SPTA1 expression using CRISPR-activation partially rescued the fragility of cells and thereby improved the enucleation efficiency. Our observations provide a potential solution for the generation of mature cells from erythroid cell lines, contributing to the future realization of the use of immortalized cell lines for transfusion therapies.


Assuntos
Núcleo Celular/efeitos dos fármacos , Eritrócitos/metabolismo , Células Eritroides/efeitos dos fármacos , Perfilação da Expressão Gênica/métodos , Inibidores de Histona Desacetilases/farmacologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Linhagem Celular , Núcleo Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Células Cultivadas , Eritrócitos/citologia , Células Eritroides/metabolismo , Ensaios de Triagem em Larga Escala/métodos , Inibidores de Histona Desacetilases/isolamento & purificação , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
8.
Life Sci ; 280: 119714, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34146554

RESUMO

BACKGROUND: Altered red blood cell (RBC) deformability has been reported in Veterans with Gulf War Illness (GWI) who endorse exercise-induced symptom exacerbation and fatigue. However, it is unknown whether altered RBC deformability is worsened secondary to exercise. OBJECTIVE: To evaluate RBC deformability in response to maximal exercise in individuals with and without GWI. METHODS: Seventeen Veterans with GWI and 11 controls performed maximal exercise and provided blood samples (pre-, immediately post- and 60-min post-exercise). We calculated RBC deformation at infinite stress (EIMAX), shear stress for half-deformation (SS1/2) and their ratio (SS1/2/EIMAX) via repeated measures ANOVA with group and time as factors. RESULTS: A moderate interaction effect (p = 0.08, η2p = 0.10), large main effect for group (p = 0.02, η2p = 0.19) and moderate main effect for time (p = 0.20, η2p = 0.06) were observed for EIMAX, but only the main effect for group reached statistical significance. Changes in SS1/2 and SS1/2/EIMAX over time were similar between cases and controls as were main effects. CONCLUSIONS: Veterans with GWI had more deformable RBCs in comparison to controls that was unaffected by maximal exercise. Future studies to confirm our findings and identify associated mechanisms are warranted.


Assuntos
Exercício Físico , Hemorreologia , Síndrome do Golfo Pérsico/sangue , Contagem de Células Sanguíneas , Deformação Eritrocítica , Eritrócitos/citologia , Eritrócitos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome do Golfo Pérsico/patologia , Veteranos
9.
Molecules ; 26(11)2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073461

RESUMO

Uncaria tomentosa (Willd.) DC is a woody climber species originating from South and Central America that has been used in the therapy of asthma, rheumatism, hypertension, and blood purification. Our previous study showed that U. tomentosa extracts altered human erythrocyte shape, which could be due to incorporation of the compounds contained in extracts into the erythrocyte membrane. The aim of the present study was to determine how the compounds contained in U. tomentosa extracts incorporate into the human erythrocyte membrane. The study has assessed the effect of aqueous and ethanolic extracts from leaves and bark of U. tomentosa on the osmotic resistance of the human erythrocyte, the viscosity of erythrocyte interior, and the fluidity of erythrocyte plasma membrane. Human erythrocytes were incubated with the studied extracts in the concentrations of 100, 250, and 500 µg/mL for 2, 5, and 24 h. All extracts tested caused a decrease in erythrocyte membrane fluidity and increased erythrocyte osmotic sensitivity. The ethanolic extracts from the bark and leaves increased viscosity of the erythrocytes. The largest changes in the studied parameters were observed in the cells incubated with bark ethanolic extract. We consider that the compounds from U. tomentosa extracts mainly build into the outer, hydrophilic monolayer of the erythrocyte membrane, thus protecting the erythrocytes against the adverse effects of oxidative stress.


Assuntos
Unha-de-Gato/química , Membrana Eritrocítica/efeitos dos fármacos , Eritrócitos/citologia , Extratos Vegetais/farmacologia , Antioxidantes/farmacologia , Relação Dose-Resposta a Droga , Etanol , Humanos , Espectroscopia de Ressonância Magnética , Fragilidade Osmótica , Estresse Oxidativo , Casca de Planta , Folhas de Planta/química , Polifenóis , Viscosidade , Água
10.
Methods Mol Biol ; 2326: 155-165, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34097267

RESUMO

This chapter describes, in detail, the operational principles and experimental design to analyze the premature death of human red blood cells (RBCs; erythrocytes). Necrosis (i.e., hemolysis), eryptosis, and necroptosis are the three types of cell death thus far known to exist in RBCs, and distinctive markers of each are well established. Here, methods based on flow cytometry are presented in an easily reproducible form. Moreover, manipulation of incubation medium to promote or inhibit certain physiological phenomena, along with a step-by-step approach to examine membrane scrambling, cell volume, surface complexity, calcium activity, oxidative stress, and signal transduction pathways are also discussed.


Assuntos
Eriptose , Eritrócitos/citologia , Citometria de Fluxo/métodos , Hemólise , Necroptose , Sinalização do Cálcio/efeitos dos fármacos , Tamanho Celular/efeitos dos fármacos , Eriptose/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Eritrócitos/patologia , Hemólise/efeitos dos fármacos , Humanos , Necroptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Testes de Toxicidade/métodos
11.
J Med Chem ; 64(11): 7359-7370, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34032114

RESUMO

Novel antibacterial agents capable of efficiently sterilizing intracellular Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) but with low cytotoxicity and low resistance development are quite appealing. In this work, three Ru(II) complexes with photolabile ligands were explored to realize such a goal. Complex 3 (5 µM) can inhibit more than 90% growth of S. aureus/MRSA that has invaded in J774A.1 cells upon visible light irradiation, being much more efficient than vancomycin. In similar conditions, negligible dark- and phototoxicity were found toward the host cells. The bactericidal activity is highly correlated with DNA covalent binding by the Ru(II) fractions generated after ligand photodissociation. Moreover, S. aureus quickly developed resistance toward vancomycin, while negligible resistance toward complex 3 even after 700 generations was obtained. These appealing results may pave a new way for fighting against intracellular antibiotic-resistant pathogens.


Assuntos
Antibacterianos/farmacologia , Complexos de Coordenação/química , Luz , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Rutênio/química , Staphylococcus aureus/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/metabolismo , Complexos de Coordenação/farmacologia , DNA/química , DNA/metabolismo , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Hemólise/efeitos dos fármacos , Humanos , Ligantes , Fotólise , Coelhos
12.
Transfusion ; 61(6): 1729-1739, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33948969

RESUMO

BACKGROUND: The average hemoglobin content of red cell concentrates (RCC) varies depending on the method of preparation. Surprisingly less data are available concerning the clinical impact of those differences. STUDY DESIGN AND METHODS: The effects of two types of RCC (RCC-A, RCC-B) on transfusion regime were compared in a non-blinded, prospective, randomized, two-period, and crossover clinical trial. RCC-A was obtained by whole blood leukoreduction and subsequent plasma removal, RCC-B removing plasma and buffy coat first, followed by leukoreduction. Eligible patients were adult, with transfusion-dependent thalassemia (TDT). RESULTS: RCC-A contained 63.9 (60.3-67.8) grams of hemoglobin per unit (median with 1st and 3rd quartile), RCC-B 54.5 (51.0-58.2) g/unit. Fifty-one patients completed the study. With RCC-B, the average pre-transfusion hemoglobin concentration was 9.3 ± 0.5 g/dl (mean ± SD), the average transfusion interval 14.2 (13.7-16.3) days, the number of RCC units transfused per year 39.3 (35.4-47.3), and the transfusion power index (a composite index) 258 ± 49. With RCC-A, the average pre-transfusion hemoglobin concentration was 9.6 ± 0.5 g/dl (+2.7%, effect size 0.792), the average transfusion interval 14.8 (14.0-18.5) days (+4.1%, effect size 0.800), the number of RCC units transfused per year 34.8 (32.1-42.5) (-11.4%, effect size -1.609), and the transfusion power index 272 ± 61 (+14.1%, effect size 0.997). All differences were statistically highly significant (p < .00001). The frequency of transfusion reactions was 0.59% with RCC-A and 0.56% with RCC-B (p = 1.000). CONCLUSION: To reduce the number of RCC units consumed per year and the number of transfusion episodes, TDT patients should receive RCC with the highest average hemoglobin content.


Assuntos
Transfusão de Eritrócitos/métodos , Hemoglobinas/análise , Talassemia/terapia , Adulto , Estudos Cross-Over , Transfusão de Eritrócitos/efeitos adversos , Eritrócitos/química , Eritrócitos/citologia , Feminino , Humanos , Procedimentos de Redução de Leucócitos , Masculino , Pessoa de Meia-Idade , Plasmaferese , Estudos Prospectivos , Talassemia/sangue , Reação Transfusional/etiologia , Resultado do Tratamento
13.
Transfusion ; 61(6): 1856-1866, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34018206

RESUMO

BACKGROUND: Various processing methodologies are routinely used to reduce volume and red blood cell content of umbilical cord blood (UCB) units collected for hematopoietic stem cell transplantation. There is limited information regarding effects of UCB processing techniques on clinical outcomes. STUDY DESIGN AND METHODS: Retrospective data analysis compared laboratory and clinical outcomes following single-unit UCB transplantation performed between 1999 and 2015. All UCB units were from St. Louis Cord Blood Bank and all were manually processed with either Hetastarch processed cord blood units (HCB) (n = 661) or PrepaCyte processed cord blood units (PCB) (n = 84). Additional sensitivity analysis focused on units transplanted from 2010 to 2015 and included 105 HCB and 84 PCB. RESULTS: There were no significant differences in patient characteristics between the two groups. Pre-freeze total nucleated and CD34+ cell counts, cell doses/kg of recipient weight, and total colony-forming units (CFUs) were higher in PCB compared with HCB. Post-thaw, the PCB group had a significantly better total nucleated cell recovery, while there were no significant differences in cell viability, CFU recovery, or CD34+ cell recovery. Primary analysis demonstrated faster neutrophil and platelet engraftment for PCB but no differences in overall survival (OS), whereas sensitivity analysis found no effect of processing method on engraftment, but better OS in the HCB group compared with PCB group. CONCLUSION: The UCB processing method had no significant impact on engraftment. However, we cannot completely exclude the effect of processing method on OS. Additional studies may be warranted to investigate the potential impact of the PCB processing method on clinical outcomes.


Assuntos
Contagem de Eritrócitos , Sangue Fetal/transplante , Adolescente , Antígenos CD34/análise , Coleta de Amostras Sanguíneas/métodos , Criança , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Eritrócitos/citologia , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Derivados de Hidroxietil Amido , Indicadores e Reagentes , Masculino , Estudos Retrospectivos
14.
Transfusion ; 61(8): 2439-2449, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33960432

RESUMO

BACKGROUND: Familial pseudohyperkalemia (FP) is characterized by an increased rate of potassium leakage in refrigerated red cells and is associated with the minor allele of the single nucleotide polymorphism rs148211042 (R723Q) in the ABCB6 gene. The study aims were to obtain the minor allele frequencies of ABCB6 variants and to measure supernatant potassium accumulation, and other red cell storage parameters, in red cell concentrates (RCC) from carriers of variant rs148211042 under standard blood bank conditions. STUDY DESIGN: Whole blood units were collected from 6 FP individuals and 11 controls and processed into RCC in additive solution. RCC were sampled and tested over cold storage for full blood count, extracellular potassium, glucose, lactate, microvesicle release, deformability, hemolysis, pH, adenosine triphosphate, and 2,3-diphosphoglycerate. RESULTS: Screening of genotyped cohorts identified that variant rs148211042 is present in 1 in 394 British citizens of European ancestry. FP RCC had significantly higher supernatant potassium at all time points from day 3 onwards (p < .001) and higher mean cell volume (p = .032) than controls. The initial rate of potassium release was higher in FP RCC; supernatant potassium reached 46.0 (23.8-57.6) mmol/L (mean [range]) by day 5, increasing to 68.9 (58.8-73.7) mmol/L by day 35. Other quality parameters were not significantly different between FP RCC and controls. CONCLUSION: These data suggest that if a blood donor has FP, reducing the RCC shelf-life to 5 days may be insufficient to reduce the risk of hyperkalemia in clinical scenarios such as neonatal large volume transfusion.


Assuntos
Preservação de Sangue/métodos , Eritrócitos/citologia , Hiperpotassemia/congênito , Potássio/análise , Transportadores de Cassetes de Ligação de ATP/genética , Eritrócitos/metabolismo , Feminino , Frequência do Gene , Humanos , Hiperpotassemia/genética , Masculino , Polimorfismo de Nucleotídeo Único
15.
Transfusion ; 61(8): 2356-2367, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34058022

RESUMO

BACKGROUND: As Western blood transfusion practices are changing, there is interest and need in anticipating the future demand of blood products and how a blood establishment can actively prepare for various long-term developments. This article provides an overview of how a scenario approach was used to prioritize key categories of drivers for the future demand of red blood cells and the organizational implications thereof for Sanquin, the Dutch national blood establishment. STUDY DESIGN AND METHODS: Based on previously identified drivers from interviews and a literature review (Step 1), we conducted scenario sessions and a survey to rank a list of drivers ("themes") with its related opportunities and threats (Step 2), to identify mitigating measures per theme through focus groups (Step 3). RESULTS: In Step 2, 10 themes were found that were classified in terms of importance and uncertainty. These were plotted on a two-dimensional graph with an ellipse to indicate the interquartile ranges per theme. Experts rated the top three most important themes to be the blood supply organization, precision medicine, and red blood cell replacements. In Step 3, focus groups identified specific mitigating measures per theme. These measures had parallel ideas, such as the need for an innovative mentality, internal and external communication and collaboration, and building Sanquin's reputation and trust with the public. CONCLUSION: Having identified the most important themes with suggestions for mitigating measures, Sanquin can take steps to become adaptive and proactive. Other blood establishments may also use a scenario approach to create contextualized long-term strategies.


Assuntos
Bancos de Sangue , Doadores de Sangue , Transfusão de Eritrócitos , Eritrócitos/citologia , Humanos , Países Baixos , Medicina de Precisão
16.
PLoS Comput Biol ; 17(5): e1008934, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33983926

RESUMO

The investigation of cell shapes mostly relies on the manual classification of 2D images, causing a subjective and time consuming evaluation based on a portion of the cell surface. We present a dual-stage neural network architecture for analyzing fine shape details from confocal microscopy recordings in 3D. The system, tested on red blood cells, uses training data from both healthy donors and patients with a congenital blood disease, namely hereditary spherocytosis. Characteristic shape features are revealed from the spherical harmonics spectrum of each cell and are automatically processed to create a reproducible and unbiased shape recognition and classification. The results show the relation between the particular genetic mutation causing the disease and the shape profile. With the obtained 3D phenotypes, we suggest our method for diagnostics and theragnostics of blood diseases. Besides the application employed in this study, our algorithms can be easily adapted for the 3D shape phenotyping of other cell types and extend their use to other applications, such as industrial automated 3D quality control.


Assuntos
Eritrócitos/citologia , Microscopia Confocal/métodos , Redes Neurais de Computação , Automação , Estudos de Casos e Controles , Eritrócitos/imunologia , Humanos , Processamento de Imagem Assistida por Computador/métodos , Reprodutibilidade dos Testes
17.
Biomolecules ; 11(4)2021 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-33917850

RESUMO

In a large variety of organisms, antimicrobial peptides (AMPs) are primary defenses against pathogens. BP100 (KKLFKKILKYL-NH2), a short, synthetic, cationic AMP, is active against bacteria and displays low toxicity towards eukaryotic cells. BP100 acquires a α-helical conformation upon interaction with membranes and increases membrane permeability. Despite the volume of information available, the action mechanism of BP100, the selectivity of its biological effects, and possible applications are far from consensual. Our group synthesized a fluorescent BP100 analogue containing naphthalimide linked to its N-terminal end, NAPHT-BP100 (Naphthalimide-AAKKLFKKILKYL-NH2). The fluorescence properties of naphthalimides, especially their spectral sensitivity to microenvironment changes, are well established, and their biological activities against transformed cells and bacteria are known. Naphthalimide derived compounds are known to interact with DNA disturbing related processes as replication and transcription, and used as anticancer agents due to this property. A wide variety of techniques were used to demonstrate that NAPHT-BP100 bound to and permeabilized zwitterionic POPC and negatively charged POPC:POPG liposomes and, upon interaction, acquired a α-helical structure. Membrane surface high peptide/lipid ratios triggered complete permeabilization of the liposomes in a detergent-like manner. Membrane disruption was driven by charge neutralization, lipid aggregation, and bilayer destabilization. NAPHT-BP100 also interacted with double-stranded DNA, indicating that this peptide could also affect other cellular processes besides causing membrane destabilization. NAPHT-BP100 showed increased antibacterial and hemolytic activities, compared to BP100, and may constitute an efficient antimicrobial agent for dermatological use. By conjugating BP100 and naphthalimide DNA binding properties, NAPHT-BP100 bound to a large extent to the bacterial membrane and could more efficiently destabilize it. We also speculate that peptide could enter the bacteria cell and interact with its DNA in the cytoplasm.


Assuntos
Anti-Infecciosos/química , Lipossomos/química , Naftalimidas/química , Oligopeptídeos/química , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Dicroísmo Circular , DNA/química , DNA/metabolismo , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Escherichia coli/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Lipossomos/metabolismo , Testes de Sensibilidade Microbiana , Oligopeptídeos/síntese química , Permeabilidade/efeitos dos fármacos , Conformação Proteica em alfa-Hélice , Espectrometria de Fluorescência , Staphylococcus aureus/efeitos dos fármacos , Termodinâmica
18.
Medicine (Baltimore) ; 100(15): e25404, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33847638

RESUMO

ABSTRACT: Previous studies have shown an independent association between increased red cell distribution width (RDW) and mortality after acute myocardial infarction (AMI). However, evidence regarding the predictive significance of repeated measures of RDW in patients with AMI remains scarce. We aimed to investigate the association between the dynamic profile of RDW and in-hospital mortality in patients with AMI.This was a cross-sectional study. We extracted clinical data from the Medical Information Mart for Intensive Care IIIV1.4 database. Demographic data, vital signs, laboratory test data, and comorbidities were collected from the database. The clinical endpoint was in-hospital mortality. Cox proportional hazards models were used to evaluate the prognostic values of basic RDW, and the Kaplan-Meier method was used to plot survival curves. Subgroup analyses were performed to measure mortality across various subgroups. The repeated-measures data were compared using a generalized additive mixed model.In total, 3101eligible patients were included. In multivariate analysis, adjusted for age, sex, and ethnicity, RDW was a significant risk predictor of in-hospital mortality. Furthermore, after adjusting for more confounding factors, RDW remained a significant predictor of in-hospital mortality (tertile 3 vs tertile 1: hazard ratio 2.3; 95% confidence interval 1.39-4.01; P for trend <.05). The Kaplan-Meier curve for tertiles of RDW indicated that survival rates were highest when RDW was ≤13.2% and lowest when RDW was ≥14.2% after adjustment for age, sex, and ethnicity. During the intensive care unit stay, the RDW of nonsurvivors progressively increased until death occurred.Our findings showed that a higher RDW was associated with an increased risk of in-hospital mortality in patients with AMI.


Assuntos
Índices de Eritrócitos , Eritrócitos/citologia , Mortalidade Hospitalar/tendências , Infarto do Miocárdio/mortalidade , Idoso , Comorbidade , Estudos Transversais , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores Socioeconômicos
19.
J Med Chem ; 64(8): 4478-4497, 2021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33792339

RESUMO

Malaria-causing Plasmodium parasites are developing resistance to antimalarial drugs, providing the impetus for new antiplasmodials. Although pantothenamides show potent antiplasmodial activity, hydrolysis by pantetheinases/vanins present in blood rapidly inactivates them. We herein report the facile synthesis and biological activity of a small library of pantothenamide analogues in which the labile amide group is replaced with a heteroaromatic ring. Several of these analogues display nanomolar antiplasmodial activity against Plasmodium falciparum and/or Plasmodium knowlesi, and are stable in the presence of pantetheinase. Both a known triazole and a novel isoxazole derivative were further characterized and found to possess high selectivity indices, medium or high Caco-2 permeability, and medium or low microsomal clearance in vitro. Although they fail to suppress Plasmodium berghei proliferation in vivo, the pharmacokinetic and contact time data presented provide a benchmark for the compound profile likely required to achieve antiplasmodial activity in mice and should facilitate lead optimization.


Assuntos
Antimaláricos/química , Isoxazóis/química , Ácido Pantotênico/análogos & derivados , Tiadiazóis/química , Triazóis/química , Animais , Antimaláricos/metabolismo , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Células CACO-2 , Proliferação de Células/efeitos dos fármacos , Estabilidade de Medicamentos , Eritrócitos/citologia , Eritrócitos/parasitologia , Feminino , Meia-Vida , Humanos , Malária Falciparum/tratamento farmacológico , Camundongos , Camundongos Endogâmicos BALB C , Ácido Pantotênico/química , Ácido Pantotênico/metabolismo , Ácido Pantotênico/farmacologia , Ácido Pantotênico/uso terapêutico , Plasmodium falciparum/efeitos dos fármacos , Plasmodium knowlesi/efeitos dos fármacos , Relação Estrutura-Atividade
20.
Methods Mol Biol ; 2227: 61-67, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33847931

RESUMO

Sheep erythrocytes (SE) are commonly used in complement functional tests. Non sensitized SE are useful to study the FH activity of cell protection. Indeed, as the cell surface of sheep erythrocytes is rich in sialic acids, Factor H (FH) is able to bind on it and therefore they represent a model of nonactivating surface. Because of their high capacity of complement regulation SE need to be modified to explore other functionality of the complement pathways, like the Complement hemolytic 50 (CH50) or the AP C3 convertase decay assays. For these tests, SE are sensitized with an anti-sheep red blood cell stroma antibody. In presence of serum or plasma complement components, sensitized SE may initiate complement cascade activation via the classic pathway explored in the CH50 assay. Sensitized SE may also be used to prepare C3b-coated SE that, with the use of buffers favoring AP, are suitable for the C3 Nef hemolytic assay and for the hemolytic assay studying the AP decay activity of FH. In this chapter we describe how to prepare SE for these different hemolytic tests.


Assuntos
Ensaio de Atividade Hemolítica de Complemento/métodos , Proteínas do Sistema Complemento/fisiologia , Citaferese/métodos , Eritrócitos/citologia , Ovinos/sangue , Animais , Separação Celular/métodos , Separação Celular/veterinária , Ativação do Complemento , Ensaio de Atividade Hemolítica de Complemento/veterinária , Proteínas do Sistema Complemento/análise , Citaferese/veterinária , Eritrócitos/imunologia , Hemólise/fisiologia , Humanos , Coelhos
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