Blood Substitutes

血液替代品
  • 文章类型: Journal Article
    背景:益生元被定义为一种不可消化的饲料物质,通过选择性刺激大肠中一种或有限数量的细菌的生长和/或活性而有益地影响宿主,从而改善宿主的健康和产品。
    目的:本研究旨在确定在Hy-LineW-36蛋鸡日粮中添加益生元低聚果糖(FOS)的效果。
    方法:总共168只Hy-LineW-36蛋鸡被分配到四个日粮水平的FOS(0、1.0、2.0、3.0g/kg日粮),在63-74期间6个重复,每个7只鸟。使用完全随机设计进行实验。
    结果:生产性能没有受到FOS补充的显著影响。体重增加随着饮食中FOS水平的增加而线性降低(p<0.01)。然而,蛋壳强度,壳厚度和Ca和P百分比没有显着影响,就像抗绵羊红细胞滴度一样,血液参数和血液代谢产物。在实验的第一阶段(63-65周),与对照组相比,3.0g/kg剂量的FOS的形状指数和Haugh单位显着增加和减少,分别为(p<0.05)。在第三和第四个时期(69-71和72-74周龄),FOS对鸡蛋内部品质性状无显著影响。此外,FOS在大多数饱和脂肪酸(SFAs)中呈线性下降,包括妄语,棕榈,脂肪酸和硬脂酸;一些单非SFA(MUFA;棕榈油酸和银杏酸),和多不饱和脂肪酸(γ-亚麻酸和二十碳三烯酸)。
    结论:在商品蛋鸡的日粮中添加不同水平的FOS对蛋鸡的表现没有显着影响,免疫反应和血液参数,而对某些内部蛋品质性状和蛋黄脂肪酸含量有显着影响。
    BACKGROUND: A prebiotic is defined as an indigestible feed substance that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the large intestine, thereby improving host health and products.
    OBJECTIVE: This study was conducted to determine the effects of supplementing prebiotic fructooligosaccharide (FOS) to the diets of Hy-Line W-36 laying hens.
    METHODS: A total of 168 Hy-Line W-36 laying hens were allocated to four dietary levels of FOS (0, 1.0, 2.0, 3.0 g/kg diet), 6 replicates of 7 birds each during 63-74. The experiment was performed using a completely randomized design.
    RESULTS: Productive performance was not significantly affected by the FOS supplementation. Body weight gain was linearly decreased with increasing FOS levels in the diet (p < 0.01). However, eggshell strength, shell thickness and Ca and p percentages were not significantly affected, as were anti-sheep red blood cell titres, blood parameters and blood metabolites. In the first period of the experiment (63-65 weeks), shape index and Haugh unit at the dose of 3.0 g/kg FOS were significantly increased and decreased in comparison with control, respectively (p < 0.05). In the third and fourth periods (69-71 and 72-74 weeks of age), the FOS had no significant effect on the internal egg quality traits. Furthermore, FOS had a linear decrease in the most saturated fatty acids (SFAs), including myristic, palmitic, margaric and stearic fatty acids; some of the mono-un-SFA (MUFA; palmitoleic and ginkgolic acids), and poly-unsaturated fatty acids (γ-linolenic and eicosatrienoic).
    CONCLUSIONS: Supplementing different levels of FOS to the diet of commercial laying hens had no significant effect on the layers\' performance, immune response and blood parameters, whereas there was a significant effect on some of the internal egg quality traits and egg yolk fatty acid contents.
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  • 文章类型: Journal Article
    血红蛋白(Hb)为基础的氧载体被研究作为一个潜在的替代或补充定期输血,特别是在危急和危及生命的情况下。这些包括偏远地区的严重创伤,战场条件,由于兼容性问题,输血不可行的情况,或者当患者基于宗教信仰拒绝输血时。本研究介绍了一种利用聚(乙二醇)(PEG)将Hb包埋在ZIF-8纳米颗粒中的新方法(即,Hb@ZIF-8NPs)。通过细致的筛选,我们获得了Hb@ZIF-8NP,Hb浓度达到创纪录的34mgmL-1。这些NP,尺寸为168nm,表现出卓越的特性:显著的95%氧合血红蛋白含量,优异的封装效率为85%,以及对Hb氧化为高铁血红蛋白(metHb)的抗性。PEG的添加成为放大ZIF-8内Hb截留的关键因素,尤其是在较高的Hb浓度下,达到前所未有的34mgmL-1。重要的是,PEG表现出保护作用,在升高的Hb浓度下,防止Hb@ZIF-8NP中的metHb转化。
    Hemoglobin (Hb)-based oxygen carriers are investigated as a potential alternative or supplement to regular blood transfusions, particularly in critical and life-threatening scenarios. These include situations like severe trauma in remote areas, battlefield conditions, instances where blood transfusion is not feasible due to compatibility concerns, or when patients decline transfusions based on religious beliefs. This study introduces a novel method utilizing poly(ethylene glycol) (PEG) to entrap Hb within ZIF-8 nanoparticles (i.e., Hb@ZIF-8 NPs). Through meticulous screening, we achieved Hb@ZIF-8 NPs with a record-high Hb concentration of 34 mg mL-1. These NPs, sized at 168 nm, displayed exceptional properties: a remarkable 95 % oxyhemoglobin content, excellent encapsulation efficiency of 85 %, and resistance to Hb oxidation into methemoglobin (metHb). The addition of PEG emerged as a crucial factor amplifying Hb entrapment within ZIF-8, especially at higher Hb concentrations, reaching an unprecedented 34 mg mL-1. Importantly, PEG exhibited a protective effect, preventing metHb conversion in Hb@ZIF-8 NPs at elevated Hb concentrations.
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  • 文章类型: Journal Article
    模仿携带血红蛋白的细胞是血液替代品的关键吗?
    Is mimicking the cells that carry hemoglobin the key to a blood substitute?
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  • 文章类型: Journal Article
    缺乏合适的供体阻碍了肺移植。以前,被认为是边缘或不足的供体被丢弃.然而,令人兴奋的新技术,例如离体肺灌注(EVLP),为肺移植提供者提供边缘供体同种异体移植物的扩展评估。这种动态评估平台导致了肺移植的增加,并允许提供者使用以前被丢弃的供体,从而扩大捐赠池。目前的灌注技术使用细胞或无细胞灌注液,两者都有明显的优点和缺点。灌注成分对于维持稳态环境至关重要,提供足够的代谢支持,减少炎症和细胞死亡,最终改善器官功能。灌注溶液必须含有足够的蛋白质浓度以维持适当的致癌压力。然而,电流灌注溶液通常导致液体通过肺内皮外渗,导致无意中的肺水肿和损伤。因此,有必要开发新的灌注溶液,以防止过度损伤,同时保持适当的细胞稳态。这里,我们描述了基于聚合人血红蛋白(PolyhHb)的氧载体作为灌注液的应用,以及可以在大鼠EVLP模型中测试该灌注液的方案.这项研究的目的是为肺移植社区提供设计和开发新的灌注解决方案的关键信息。以及在临床相关的翻译移植模型中测试它们的适当方案。
    Lung transplantation is hampered by the lack of suitable donors. Previously, donors that were thought to be marginal or inadequate were discarded. However, new and exciting technology, such as ex vivo lung perfusion (EVLP), offers lung transplant providers extended assessment for marginal donor allografts. This dynamic assessment platform has led to an increase in lung transplantation and has allowed providers to use donors that were previously discarded, thus expanding the donor pool. Current perfusion techniques use cellular or acellular perfusates, and both have distinct advantages and disadvantages. Perfusion composition is critical to maintaining a homeostatic environment, providing adequate metabolic support, decreasing inflammation and cellular death, and ultimately improving organ function. Perfusion solutions must contain sufficient protein concentration to maintain appropriate oncotic pressure. However, current perfusion solutions often lead to fluid extravasation through the pulmonary endothelium, resulting in inadvertent pulmonary edema and damage. Thus, it is necessary to develop novel perfusion solutions that prevent excessive damage while maintaining proper cellular homeostasis. Here, we describe the application of a polymerized human hemoglobin (PolyhHb)-based oxygen carrier as a perfusate and the protocol in which this perfusion solution can be tested in a model of rat EVLP. The goal of this study is to provide the lung transplant community with key information in designing and developing novel perfusion solutions, as well as the proper protocols to test them in clinically relevant translational transplant models.
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  • 文章类型: Journal Article
    该综述介绍了基于全氟有机化合物(PFC)的血液替代品开发的结果。描述了PFC的局限性,因此暂停了进一步的开发。所提供的数据使我们能够想象一种基于PFC创建最佳药物的可能方法。应使用化学惰性的全氟组分-全氟烃和叔全氟胺。然而,为了乳化和稳定乳液,需要其他类型的有效和化学无关的表面活性剂,这些表面活性剂不与氧气和药物的其他成分相互作用。
    The review presents the results of the blood substitute development based on perfluororganic compounds (PFC). The limitations of PFC due to which their further development was suspended are described. The presented data allows us to imagine a possible way to create optimal drugs based on PFC. Chemically inactive perfluorocomponents should be used - perfluorinated hydrocarbons and tertiary perfluorinated amines. However, in order to emulsify and stabilize the emulsion, other types of effective and chemically indifferent surfactants that do not interact with oxygen and other components of the drug are needed.
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  • 文章类型: Journal Article
    氧气是生命所必需的,在维持正常生理功能和治疗疾病中起着关键的作用。已经研究并开发了基于血红蛋白的氧载体(HBOC),因为它们具有相似的携氧能力,可以替代氧气运输中的红细胞(RBC)。然而,HBOCs的应用受到血管活性的阻碍,氧化毒性,和相对较短的循环半衰期。随着纳米技术的进步,Hb封装,吸收,生物缀合,诱捕,和附着到纳米材料已被用于制备纳米材料相关的HBOCs,以解决这些挑战,并在一些生物医学和治疗环境中的应用。本文就该类纳米材料相关HBOCs在失血性休克领域的研究进展作一综述。缺血性卒中,癌症,伤口愈合,并对未来的研究方向进行了推测。与纳米材料相关的HBOCs的进步有望在血液替代品方面取得重大突破,使其广泛用于临床疾病的治疗。
    Oxygen is necessary for life and plays a key pivotal in maintaining normal physiological functions and treat of diseases. Hemoglobin-based oxygen carriers (HBOCs) have been studied and developed as a replacement for red blood cells (RBCs) in oxygen transport due to their similar oxygen-carrying capacities. However, applications of HBOCs are hindered by vasoactivity, oxidative toxicity, and a relatively short circulatory half-life. With advancements in nanotechnology, Hb encapsulation, absorption, bioconjugation, entrapment, and attachment to nanomaterials have been used to prepare nanomaterial-related HBOCs to address these challenges and pend their application in several biomedical and therapeutic contexts. This review focuses on the progress of this class of nanomaterial-related HBOCs in the fields of hemorrhagic shock, ischemic stroke, cancer, and wound healing, and speculates on future research directions. The advancements in nanomaterial-related HBOCs are expected to lead significant breakthroughs in blood substitutes, enabling their widespread use in the treatment of clinical diseases.
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  • 文章类型: Journal Article
    高热量的广泛采用,高脂肪,高蔗糖饮食(HFHSD)已成为全球健康问题,特别是由于它们与心血管疾病和代谢紊乱有关。这些合并症增加了对病毒感染和创伤的严重后果的易感性,与创伤相关的事件对全球死亡率有显著影响。这种情况强调了对可靠血液供应的迫切需要。最近的研究集中在高分子量(MW)聚合的人血红蛋白(PolyhHb)作为红细胞(RBC)的有希望的替代品,在以前的研究中显示出令人鼓舞的结果。鉴于代谢紊乱和创伤相关健康问题的重叠,评估PolyhHb输血的潜在毒性至关重要,特别是在代表这些弱势群体的模型中。这项研究评估了PolyhHb交换输血对由于12周HFHSD方案而发生代谢紊乱的豚鼠的影响。豚鼠,用PolyhHb或较低分子量的聚合牛血红蛋白进行20%的血液体积交换输血,氧球蛋白.结果显示,无论是PolyhHb和氧球蛋白输血导致肝损伤,在饲喂HFHSD的动物中观察到更明显的效果。此外,心功能障碍的标志物表明在输注氧球蛋白后,HFHSD和正常饮食组均有心脏损伤的迹象.这项研究强调了预先存在的代谢紊乱如何加剧基于血红蛋白的氧载体(HBOC)的潜在副作用。重要的是,与上一代低MWPolyhHb相比,新一代高MWPolyhHb显示出更低的心脏毒性,被称为氧球蛋白,即使在预先存在内皮和代谢挑战的模型中。
    The widespread adoption of high-calorie, high-fat, high-sucrose diets (HFHSD) has become a global health concern, particularly due to their association with cardiovascular diseases and metabolic disorders. These comorbidities increase susceptibility to severe outcomes from viral infections and trauma, with trauma-related incidents significantly contributing to global mortality rates. This context underscores the critical need for a reliable blood supply. Recent research has focused on high molecular weight (MW) polymerized human hemoglobin (PolyhHb) as a promising alternative to red blood cells (RBCs), showing encouraging outcomes in previous studies. Given the overlap of metabolic disorders and trauma-related health issues, it is crucial to assess the potential toxicity of PolyhHb transfusions, particularly in models that represent these vulnerable populations. This study evaluated the effects of PolyhHb exchange transfusion in guinea pigs that had developed metabolic disorders due to a 12-week HFHSD regimen. The guinea pigs, underwent a 20 % blood volume exchange transfusion with either PolyhHb or the lower molecular weight polymerized bovine hemoglobin, Oxyglobin. Results revealed that both PolyhHb and Oxyglobin transfusions led to liver damage, with a more pronounced effect observed in HFHSD-fed animals. Additionally, markers of cardiac dysfunction indicated signs of cardiac injury in both the HFHSD and normal diet groups following the Oxyglobin transfusion. This study highlights how pre-existing metabolic disorders can exacerbate the potential side effects of hemoglobin-based oxygen carriers (HBOCs). Importantly, the newer generation of high MW PolyhHb showed lower cardiac toxicity compared to the earlier generation low MW PolyhHb, known as Oxyglobin, even in models with pre-existing endothelial and metabolic challenges.
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  • 文章类型: Journal Article
    出血性休克是世界范围内死亡的主要原因。输血可用于治疗严重失血的患者,但捐献的红细胞(RBC)有一些限制,限制了其可用性和使用。为了解决与捐赠的红细胞相关的问题,已经开发了几种基于血红蛋白的无细胞氧载体(HBOC)来恢复血液最重要的功能:氧转运。一种有前途的HBOC是天麻(LtEc)的天然细胞外血红蛋白(即赤霉素)。这项研究的目的是通过冻干LtEc,然后在高温下测试其稳定性,从而最大程度地提高LtEc的便携性。为了防止氧化,筛选了几种冷冻保护剂,以确定冻干的最佳配方,该配方可以最大程度地减少血红素铁的氧化并最大程度地提高回收率。此外,样品在储存前也脱氧以减少自动氧化,而在含有抗坏血酸的溶液中的再悬浮显示部分还原在储存期间已氧化的LtEc(例如从42%Fe3+至11%Fe3+)。对重新悬浮的LtEc的氧平衡和大小的分析表明,storage,和再悬浮过程不影响氧传输性质或LtEc的结构,甚至在40℃下储存6个月后。总之,这些努力产生了一种货架稳定的LtEc粉末,可以在高温下长时间储存,但是,未来的动物研究将有必要证明重新悬浮的产品是体内安全有效的氧转运蛋白。
    Haemorrhagic shock is a leading cause of death worldwide. Blood transfusions can be used to treat patients suffering severe blood loss but donated red blood cells (RBCs) have several limitations that limit their availability and use. To solve the problems associated with donated RBCs, several acellular haemoglobin-based oxygen carriers (HBOCs) have been developed to restore the most important function of blood: oxygen transport. One promising HBOC is the naturally extracellular haemoglobin (i.e. erythrocruorin) of Lumbricus terrestris (LtEc). The goal of this study was to maximise the portability of LtEc by lyophilising it and then testing its stability at elevated temperatures. To prevent oxidation, several cryoprotectants were screened to determine the optimum formulation for lyophilisation that could minimise oxidation of the haem iron and maximise recovery. Furthermore, samples were also deoxygenated prior to storage to decrease auto-oxidation, while resuspension in a solution containing ascorbic acid was shown to partially reduce LtEc that had oxidised during storage (e.g. from 42% Fe3+ to 11% Fe3+). Analysis of the oxygen equilibria and size of the resuspended LtEc showed that the lyophilisation, storage, and resuspension processes did not affect the oxygen transport properties or the structure of the LtEc, even after 6 months of storage at 40 °C. Altogether, these efforts have yielded a shelf-stable LtEc powder that can be stored for long periods at high temperatures, but future animal studies will be necessary to prove that the resuspended product is a safe and effective oxygen transporter in vivo.
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  • 文章类型: Journal Article
    背景:严重失血性休克的治疗通常包括用血液制品进行止血复苏。然而,后勤方面的限制常常妨碍了像全血这样的常用血液制品的广泛分布。当更常规的血液制品不容易获得时,货架稳定的血液制品和血液替代品准备能够有效地复苏失血性休克中的个体。
    方法:将目的饲养的成年犬(n=6)麻醉,仪表化,并遭受失血性休克(MAP<50mmHg或40%的血容量损失)。然后用五种复苏产品之一对每只狗进行复苏:(1)乳酸林格氏溶液和hetastarch(LRS/heta),(2)犬冷冻全血(CWB),(3)新鲜冷冻血浆(FFP)和包装红细胞(pRBC),(4)犬冻干血浆(FDP)和基于血红蛋白的氧载体(HBOC),或(5)HBOC/FDP和犬冻干血小板(LyoPLT)。允许每只狗在出血复苏事件后恢复,然后经历另一次出血事件并用不同的产品复苏,直到每只狗用每种产品复苏。
    结果:当确定动物处于休克状态时,由休克指数<1定义,FFP/pRBC(n=5,83.7±4.5)和FDP/HBOC+LyoPLT(n=4,87.8)的MAP(mmHg)值(平均值±标准误差)更高。±2.1)与WB(n=4,66.0±13.1)相比。在用HBOC和FDP复苏的狗中,肌酐短暂增加。与LRS/heta和CWB相比,用HBOC和FDP产品复苏的狗的白蛋白和碱过量增加(p<0.01)。
    结论:与犬CWB相比,货架稳定的血液制品组合在解决休克方面具有优势。需要进一步的研究来确定这些储存稳定的产品组合在其他出血模型中的可靠性和有效性,这些模型包括组织损伤以及自然发生的创伤。
    方法:这是一项证据水平为IV的治疗/护理管理研究。
    BACKGROUND: Treatment of severe hemorrhagic shock typically involves hemostatic resuscitation with blood products. However, logistical constraints often hamper the wide distribution of commonly used blood products like whole blood. Shelf-stable blood products and blood substitutes are poised to be able to effectively resuscitate individuals in hemorrhagic shock when more conventional blood products are not readily available.
    METHODS: Purpose-bred adult dogs (n = 6) were anesthetized, instrumented, and subjected to hemorrhagic shock (mean arterial pressure <50 mm Hg or 40% blood volume loss). Then each dog was resuscitated with one of five resuscitation products: (1) lactated ringers solution and hetastarch (LRS/Heta), (2) canine chilled whole blood (CWB), (3) fresh frozen plasma (FFP) and packed red blood cells (pRBC), (4) canine freeze-dried plasma (FDP) and hemoglobin-based oxygen carrier (HBOC), or (5) HBOC/FDP and canine lyophilized platelets (LyoPLT). Each dog was allowed to recover after the hemorrhage resuscitation event and was then subjected to another hemorrhage event and resuscitated with a different product until each dog was resuscitated with each product.
    RESULTS: At the time when animals were determined to be out of shock as defined by a shock index <1, mean arterial pressure (mmHg) values (mean ± standard error) were higher for FFP/pRBC (n = 5, 83.7 ± 4.5) and FDP/HBOC+LyoPLT (n = 4, 87.8 ± 2.1) as compared with WB (n = 4, 66.0 ± 13.1). A transient increase in creatinine was seen in dogs resuscitated with HBOC and FDP. Albumin and base excess increased in dogs resuscitated with HBOC and FDP products compared with LRS/heta and CWB ( p < 0.01).
    CONCLUSIONS: Combinations of shelf-stable blood products compared favorably to canine CWB for resolution of shock. Further research is needed to ascertain the reliability and efficacy of these shelf-stable combinations of products in other models of hemorrhage that include a component of tissue damage as well as naturally occurring trauma.
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  • 文章类型: Case Reports
    背景:一名54岁的西班牙裔OPOS女性,具有已知的抗Rh17抗体病史,被诊断为费城染色体阳性(Ph+)急性淋巴细胞白血病(ALL)。Rh17,也称为Hr0,是由RhCE蛋白上的几个表位组成的高频抗原。抗Rh17抗体可以由缺失或不同C/c的个体产生,E/e抗原。鉴于胎儿和新生儿溶血病(HDFN)的多个病例报告,抗Rh17抗体具有临床意义。考虑到100,000人中只有1人是Rh17阴性的,为抗Rh17患者寻找兼容的单位可能特别困难。
    方法:由美国稀有捐赠者计划(ARDP)进行无导线的兼容单位搜索。化疗诱导后,尽管施用红细胞生成刺激剂,患者的血红蛋白继续下降至最低点2.8g/dL。在这里,我们报告了向患有严重症状性贫血的患者输注不相容的pRBC。HBOC-201(Hemopure)是在紧急研究新药(IND)申请下,根据食品和药物管理局(FDA)的紧急同情/扩展访问指定获得和管理的。
    结论:这种情况下的总体困难包括寻找兼容单位的挑战,在患有严重贫血的患者中输注不相容单位并获得血液制品替代品的困境。该病例报告证明了HBOC-21在治疗危及生命的贫血中的成功使用。
    BACKGROUND: A 54-year-old Hispanic OPos female with known history of anti-Rh17 antibodies was diagnosed with Philadelphia-Chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). Rh17, also known as Hr0, is a high-frequency antigen composed of several epitopes on the RhCE protein. Anti-Rh17 antibodies can be made by individuals with missing or varied C/c, E/e antigens. Anti-Rh17 antibodies are clinically significant given multiple case reports of hemolytic disease of the fetus and newborn (HDFN). Finding compatible units for patients with anti-Rh17 can be particularly difficult given that only 1 in 100,000 people are Rh17 negative.
    METHODS: Search for compatible units was conducted by the American Rare Donor Program (ARDP) with no leads. After chemotherapy induction and despite erythropoiesis stimulating agent administration, the patient\'s hemoglobin continued to trend down to a nadir of 2.8 g/dL. Here we report transfusion of incompatible pRBC to this patient with critically symptomatic anemia. HBOC-201 (Hemopure) was obtained and administered under an emergency compassionate/expanded access designation from the Food and Drug Administration (FDA) under an emergency Investigational New Drug (IND) application.
    CONCLUSIONS: Overall difficulties in this case included the challenge of finding compatible units, dilemma of transfusing incompatible units in a patient with severe anemia and obtaining alternatives to blood products. This case report demonstrates the successful use of HBOC-21 in treating life-threatening anemia.
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