New Applications of HBOC-201: A 25-Year Review of the Literature

If not cured promptly, tissue ischemia and hypoxia can cause serious consequences or even threaten the life of the patient. Hemoglobin-based oxygen carrier-201 (HBOC-201), bovine hemoglobin polymerized by glutaraldehyde and stored in a modified Ringer's lactic acid solution, has been investigated as a blood substitute for clinical use. HBOC-201 was approved in South Africa in 2001 to treat patients with low hemoglobin (Hb) levels when red blood cells (RBCs) are contraindicated, rejected, or unavailable. By promoting oxygen diffusion and convective oxygen delivery, HBOC-201 may act as a direct oxygen donor and increase oxygen transfer between RBCs and between RBCs and tissues. Therefore, HBOC-201 is gradually finding applications in treating various ischemic and hypoxic diseases including traumatic hemorrhagic shock, hemolysis, myocardial infarction, cardiopulmonary bypass, perioperative period, organ transplantation, etc. However, side effects such as vasoconstriction and elevated methemoglobin caused by HBOC-201 are major concerns in clinical applications because Hbs are not encapsulated by cell membranes. This study summarizes preclinical and clinical studies of HBOC-201 applied in various clinical scenarios, outlines the relevant mechanisms, highlights potential side effects and solutions, and discusses the application prospects. Randomized trials with large samples need to be further studied to better validate the efficacy, safety, and tolerability of HBOC-201 to the extent where patient-specific treatment strategies would be developed for various clinical scenarios to improve clinical outcomes.

ARTIFICIAL BLOOD: AN ACCOUNT OF HBOC AND PFC APPROACHES

In the field of medicine, artificial blood is an innovative concept, where specially designed compounds are developed to perform the task of transport and delivery of oxygen. Hence, it can potentially replace the function of allogenic human blood transfusion. Several molecules have been developed using several approaches. However, with continuous refinements in the past few decades, the ideal blood substitute would likely be Hemoglobin Based Oxygen Carrier. The benefits of HBOCs are tremendous, as they do not require compatibility testing or tissue matching, are non-pathogenic, have a long shelf life, and can even be stored at room temperature. The advent of artificial blood is projected to have a remarkable impact on medical care in the future. While it will complement blood transfusion safely, it will also create a stable supply of effective products. It is likely to reduce the requirements of blood transfusions drastically in settings of surgery, trauma, or warfare.

RESEARCH OF THE EFFECT OF A NEW ANTIHYPOXANT AND ANTIOXIDANT AGENT IN EXPERIMENTAL HYPOXIA CAUSED BY ACUTE BLOOD LOSS

Aim. To study the antihypoxic and antioxidant effect of the new blood substitute «Rheoambrasol» in acute blood loss.Material and methods. The experiments were carried out on 60 rats, in which the experimental model of acute blood loss was reproduced. The effectiveness of using the new blood substitute «Rheoambrasol” in acute blood loss was determined in comparison with the drug “Rheopolyglyukin”.Results. The results obtained, it can be seen that blood loss is accompanied by hypoxia, as evidenced by the concentration of hypoxia-inducible factor (HIF-1α), which increased in the second group by 4.1 times. After the infusion of “Rheoambrasol”, the content of hypoxia-inducible factor HIF-1α in blood plasma decreased 2.9 times, compared with the value after blood loss, which was 44.4% lower than after the infusion of the drug “Rheopolyglucin”. After the use of the drug “Rheoambrasol”, the balance of lipid peroxidation activity/ antioxidant system activity (LPO/AOS) in the blood, myocardium and liver was restored. Conclusion. The new drug “Rheoambrasol” has a pronounced antihypoxant effect in acute blood loss, which is manifested in the ability to reduce the content of HIF-1α in the blood of experimental animals.The introduction of “Rheoambrasol” in acute blood loss effectively inhibits lipid peroxidation processes in the blood, myocardium and liver and increases the activity of AOS enzymes, which indicates its antioxidant effect.

Stability of Maleimide-PEG and Mono-Sulfone-PEG Conjugation to a Novel Engineered Cysteine in the Human Hemoglobin Alpha Subunit

In order to use a Hemoglobin Based Oxygen Carrier as an oxygen therapeutic or blood substitute, it is necessary to increase the size of the hemoglobin molecule to prevent rapid renal clearance. A common method uses maleimide PEGylation of sulfhydryls created by the reaction of 2-iminothiolane at surface lysines. However, this creates highly heterogenous mixtures of molecules. We recently engineered a hemoglobin with a single novel, reactive cysteine residue on the surface of the alpha subunit creating a single PEGylation site (βCys93Ala/αAla19Cys). This enabled homogenous PEGylation by maleimide-PEG with >80% efficiency and no discernible effect on protein function. However, maleimide-PEG adducts are subject to deconjugation via retro-Michael reactions and cross-conjugation to endogenous thiol species in vivo. We therefore compared our maleimide-PEG adduct with one created using a mono-sulfone-PEG less susceptible to deconjugation. Mono-sulfone-PEG underwent reaction at αAla19Cys hemoglobin with > 80% efficiency, although some side reactions were observed at higher PEG:hemoglobin ratios; the adduct bound oxygen with similar affinity and cooperativity as wild type hemoglobin. When directly compared to maleimide-PEG, the mono-sulfone-PEG adduct was significantly more stable when incubated at 37°C for seven days in the presence of 1 mM reduced glutathione. Hemoglobin treated with mono-sulfone-PEG retained > 90% of its conjugation, whereas for maleimide-PEG < 70% of the maleimide-PEG conjugate remained intact. Although maleimide-PEGylation is certainly stable enough for acute therapeutic use as an oxygen therapeutic, for pharmaceuticals intended for longer vascular retention (weeks-months), reagents such as mono-sulfone-PEG may be more appropriate.

Application of DNA Containing Forensic Blood Substitute in the Bloodstain Pattern Analysis

We were able to diversify blood substitutes that emphasized the existing physical characteristics by adding the synthetic DNA, which was designed and produced in this study, to developed blood substitute. By doing so, we could improve the availability of developed blood substitute to the point where it can be identified similarly as in DNA analysis from the human blood.

Blood substitute family as a socio-cultural environment for a child left without care, conditions and features of its professional support

The article discusses the features of the blood substitute family as a socio-cultural environment of the child and the importance of professional support for its effective and successful functioning. The blood substitute family is the most common form of family placement of orphaned children, children left without parental care, throughout the historical period and currently accounts for more than 60% of all existing substitute families. The blood substitute family is a specific category within the substitute care. The peculiarities of its creation and functioning determine the topicality of specific professional support for the family. Psychological and pedagogic support is most often expressed in the official legally approved training of potential foster parents and support for families of this category. At the same time, while there is an objectively urgent need for support and assistance, problems still exist which are associated with the optionality of these services to close relatives who adopted children for family placement, their implementation in the framework of leisure activities, low motivation, fears and distrust of the official professional service. The socio-pedagogic conditions given in the article, which determine the forms and content of professional support for all members of the blood substitute family, determine the effectiveness of the service's specialists in terms of preventing second orphanhood and assistance of providing the prosperity for all its members.

PROSPECTS FOR TREATMENT AND LIFE-SAVING FOR PATIENTS WITH CORONAVIRUS INFECTION

The article is devoted to the analysis of means of symptomatic treatment of coronavirus infection. Pathogenesis and symptoms of damage to organs and systems are considered. The main mechanisms of disruption of blood supply to organs and tissues are noted. The history of the development and use of perfluorane in disorders of gas exchange in the lungs and the function of red blood cells to transport oxygen is presented. Data on the effectiveness of the use of blood substitute in medical practice is considered. The properties and qualities of perfluorane and the mechanisms of its action to improve the oxygen supply of organs and tissues are considered. Evidence of the use of perfluorane in various diseases is given. The prospect of using perfluorane for the treatment of patients with coronavirus infection has been shown.