Effects of Human Hemoglobin on Bacterial Endotoxin In Vitro and In Vivo
Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison in Endotoxin in Health and Disease, 2020
Our data suggest that hemoglobin-based blood substitutes, which are currently undergoing clinical trials (53,54), may intensify the potentially fatal effects of the sepsis syndrome in patients with trauma, infection, or hypotension who receive hemoglobin for red blood cell replacement. Others have also recently expressed concern about the potential danger of administration of hemoglobin-based red blood cell substitutes to patients with sepsis, ischemia, or shock (the latter two clinical conditions can predispose to the development of en dotoxemia, even if endotoxin is not the precipitating cause of ischemia or hypotension) (13,55,56). There fore, Hb should be administered to such patients with caution and thorough serial physiological observations performed in order to detect any worsening of signs or symptoms that may be attributable to endotoxemia and the sepsis syndrome.
Concepts of Replacement Therapy: Blood Components, Blood Derivatives, and Medications
Harold R. Schumacher, William A. Rock, Sanford A. Stass in Handbook of Hematologic Pathology, 2019
Since no blood substitute is currently available, only a brief mention will be made here. Stroma-free hemoglobin solutions, in which free hemoglobin (obtained from outdated human or porcine red blood cells) has been separated from red blood cell membranes, must be modified to prevent the significant side effects associated with its use. However, the efficient oxygen-carrying capabilities of this product hold great promise. Several manufacturers have products now in advanced clinical trials. Hemoglobin produced by recombinant DNA techniques is also under investigation. Perflourochemicals have also been studied as a plasma oxygen carrier. It should be noted that these products can only serve to substitute for one function of blood, oxygen transport, and will not replace red blood cell transfusions in most settings (29).
The Twentieth Century
Arturo Castiglioni in A History of Medicine, 2019
transfusion of whole blood or plasma or blood substitutes (known since the seventeenth century) has been so greatly advanced in recent years that it constitutes one of the important therapeutic achievements of the twentieth century. The early attempts, in spite of frequent untoward results, had not been forgotten, though it was not until the nineteenth century that study of the subject was again resumed (Bichat, 1805; Blundell’s indirect syringe method, 1824; Prevost’s and Dumas’s use of defibrinated blood, 1821). Success with transfusions in animals kept alive human attempts until in the 1870’s new enthusiasm developed. O. hasse, regarding defibrinated blood as half dead, advocated whole lamb’s blood (1874), and even whole milk had its supporters on both sides of the Atlantic. In the light of present knowledge one wonders how such fallacious and dangerous methods could even have found their way into the medical print of the period. Landsteiner’s discovery (1900) of the four more or less incompatible groups of human blood explained previous disasters and first permitted a logical approach to the subject. Crile (1906) was one of the first to make practical use of this discovery with his direct method of suturing the donor’s artery to the recipient’s vein. However, when it was found by Albert hustin (b. 1882), in 1914; Luis agote, of Buenos Aires, in 1914; R. lewisohn (b. 1875), in 1915, and others that blood coagulation could be harmlessly prevented by sodium citrate, the indirect method of drawing the blood into a receptacle and then injecting it into the vein soon came into general use. This in turn paved the way for storage of blood, first by Rous and Turner, (1916), later by D. N. belanki (1928) of Moscow, and J. tenconi and O. R. palazzo (1934) of Buenos Aires. Conserved blood in human treatment was used by O. H. Robertson (1918), later by S. S. yudin of Moscow (1930).
Ferulic acid modification enhances the anti-oxidation activity of natural Hb in vitro
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Donglai Qi, Qian Li, Chen Chen, Xiang Wang
Artificial blood substitutes aim to overcome the aforementioned drawbacks of collecting, storing, testing and trans-fusing donated human RBC units, and to provide immediate and safe oxygen delivery for a variety of clinical applications. Most well-developed artificial blood substitutes are “RBC substitutes” or, in another word, oxygen carriers which have several common features: (i) they are fully synthetic products or are derived from mammalian blood with long shelf-lives and from abundant source material; (ii) they do not require blood type matching before transfusion; (iii) they can be easily pasteurized to eliminate microbial or viral infection; and (iv) they can bind oxygen with high affinity and enable rapid tissue delivery. As an appropriate substitute of RBC, haemoglobin-based oxygen carriers (HBOCs) have been developed for transfusion medicine in recent years [4,5]. HBOCs are generally classified into two types: One is the acellular type. Based on different conjugation chemistries, three types of acellular HBOC have been developed and forwarded to human clinical trials, including cross-linked, polymerized, and conjugated (i.e. surface-modified) Hbs [6–9]. Another kind is the cellular-type systems. Although they are not yet in clinical trials, they have been shown to have excellent O2 carrying ability and good safety profiles in vivo [10–13]. The usefulness and safety of HBOCs have been demonstrated by many researchers in various fields such as biochemistry, physiology and toxicology [14,15].
Increasing the stability of Lumbricus terrestris erythrocruorin via poly(acrylic acid) conjugation
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Kyle Spivack, Matthew Tucker, Devon Zimmerman, Matthew Nicholas, Osheiza Abdulmalik, Noelle Comolli, Jacob Elmer
In addition to being thermally stable, blood substitutes must also be sterilized prior to transfusion. It is possible to remove most microbes with a 0.22 μm filter, but viruses are typically much smaller and are eliminated via denaturation at high temperatures (e.g. autoclaving or pasteurization). Since a previous study by Mudhivarthi et al. [12] showed that conjugating human haemoglobin (HbA) to PAA produced conjugates that could be autoclaved without denaturation or aggregation, we performed similar experiments with native LtEc, LP, and LPE samples, as shown in Figure 5. As expected, autoclaving the native protein yielded a fully denatured and oxidized (brown) aggregate (Figure 5(A)). In contrast, the LP and LPE samples could be autoclaved without aggregating, but they both changed color from red to brown (Figure 5(B,C)) and their absorbance spectra showed a complete loss of the Q-bands (data not shown).
The role of artificial cells in the fight against COVID-19: deliver vaccine, hemoperfusion removes toxic cytokines, nanobiotherapeutics lower free radicals and pCO2 and replenish blood supply
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2022
Thus, PolyHb-SOD-CAT-CA can help to solve the critical and severe donor blood supply crisis, especially for the following situations [63,64].Cardic. Cancer and other urgent Surgery that requires the use of donor blood.Accidents, disasters, or conflicts resulting in severe blood loss require an immediate urgent blood transfusion.Arterial obstruction can lead to heart attack and stroke. Blood substitute being a solution can perfuse through partially obstructed vessels to reach the heart and brain.There are many medical conditions that may need donor blood. However, blood substitutes are only good for shorter term use in more acute conditions.If condition does not allow for rbc to be stored in the frig, lyophilised nanobiotherapeutic can be stored at room temperature for 1 year [65].
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