Blood substitutes for

A large number of perfluorinated heterocyclic compounds was prepared (mostly using ECF technology) in 1970-1990 during the quest for the best materials to be used as oxygen carriers in perfluorocarbon emulsions, so-called blood substitutes (for detailed review on this effort, see Ref. 34). The list of synthesized materials includes perfluorinated A-alkyl(cycloalkyl) pyrrolidines, oxazolidines, piperidines and... 

Microemulsions containing fluorocarbons have been investigated as blood substitutes. For example, Cecutti et al. [55] studied these aspects of microemulsions and found that although the inherent incompatibility between hydrocarbons and fluorocarbons puts some demands on the surfactant to be used, the resulting microemulsion (prepared from fluorinated oil, water, and an nonionic surfactant) displayed oxygen absorption similar to that of blood, and at the same time the toxicity was limited and the microemulsions appeared to be well tolerated. 

The possible applications of the models include blood substitutes for clinical use in humans [274]. An important recent advance was made by Tsuchida et al. [291,292], who prepared membrane-bound picket-fence iron porphyrins for in vivo testing. The dioxygen binding rate and affinity were found to be similar to those of red blood cells [293] or erythrocytes in suspension [294]. 

Gaucher, C. and Menu, P. How to evaluate blood substitutes for endothelial cell toxicity. Antioxid... 

Poly(vinyl pyrrolidone). Another commercial polymer with significant usage is PVP (7). It was developed ia World War II as a plasma substitute for blood... 

Medical appHcations of PFC emulsions for organ perfusion and intravenous uses have received much attention in recent years. The first commercial blood substitute (Fluosol DA 20%, trademark of the Green Cross Corp.) employed perfluorodecalin, and improved, second generation products based on this PFC, or perfluorooctylbromide, are now under development (20,21). The relatively high oxygen dissolving capabiHty of PFCs undedies these appHcations (see Blood, artificial). 

Perfluorinated compounds are also potentially useful as inert reaction media, particularly when one of the reactants is gaseous. The high solubiHty of oxygen and carbon dioxide in perfluorinated Hquids has allowed their use as blood substitutes (41) and as oxygenation media for biotechnology (42). One product, Fluosol DA (43) (Green Cross Corp.), has been commercialized, and there is an abundant patent art in this area (see Blood, artificial). 

Other biomedical and biological appHcations of mictocapsules continue to be developed. For example, the encapsulation of enzymes continues to attract interest even though loss of enzyme activity due to harshness of the encapsulation protocols used has been a persistent problem (59). The use of mictocapsules in antibody hormone immunoassays has been reviewed (60). The encapsulation of hemoglobin as a ted blood substitute has received much attention because of AIDS and blood transfusions (61). 

Albumin. Investigation iato the safety of bovine plasma for clinical use was undertaken ia the eady 1940s ia anticipation of wartime need (26). Using modem proteia chemistry methods, including electrophoresis and ultracentrifugation, it was shown that most of the human adverse reactions to blood substitutes were caused by the globulin fraction and that albumin was safe for parenteral use. Human albumin is now used extensively as a plasma expander ia many clinical settings. 

AH of the reactions considered to be useful in the production of hemoglobin-based blood substitutes use chemical modification at one or more of the sites discussed above. Table 2 Hsts the different types of hemoglobin modifications with examples of the most common reactions for each. Differences in the reactions are determined by the dimensions and reactivity of the cross-linking reagents. Because the function of hemoglobin in binding and releasing... 

Outdated Human Blood. If clinical efficacy and safety of hemoglobin solutions can be shown, the demand for product would soon outstrip the supply of outdated human blood. About 12 million units of blood (1 unit 480 mL) are used in the United States each year, and only about 500,000 outdate. The primary use of blood is in intraoperative and emergency settings. The quantity of blood available for use in production of blood substitutes depends on safety and efficient usage of blood products as well as on the demands on blood suppHes. 

Dozens of compounds have been used in in vivo fluonne NMR and MRI studies, chosen more for their commercial availability and established biochemistry than for ease of fluonne signal detection [244] Among the more common of these are halothane and other fluormated anesthetics [245, 246], fluorodeoxyglucose [242 243], and perfluormated synthetic blood substitutes, such as Fluosol [246], a mixture of perfluorotnpropylamine and perfluorodecahn Results have been Imut-ed by chemical shift effects (multiple signals spread over a wide spectral range) and long acquisition times... 

The IV solutions of plasma expanders include hetastarch (Hespan), low-molecular-weight dextran (Dextran 40), and high-molecular-weight dextran (Dextran 70, Dextran 75). Plasma expanders are used to expand plasma volume when shock is caused by bums, hemorrhage surgery, and otiier trauma and for prophylaxis of venous thrombosis and diromboembolism. When used in die treatment of shock, plasma expanders are not a substitute for whole blood or plasma, but tiiey are of value as emergency measures until die latter substances can be used. 

An extreme example of slime production is found in Leuconostoc dextranicum and L. mesenteroides where so much carbohydrate, called dextran, may be produced that the whole medium in which these cells are growing becomes almost gel-like. This phenomenon has caused pipe blockage in sugar refineries and is deliberately encouraged for the production of dextran as a blood substitute (Chapter 25). 

Other important examples are blood and blood products, which are collected and processed in sterile containers, and plasma substitutes, for example dextrans and degraded gelatin. Dextrans, glucose polymers consisting essentially of (1 - 6) a-links, are produced as a result of the biochemical activities of certain bacteria of the genus Leuconostoc, e.g. L. mesenteroides (see Chapter 25). 

Because process mixtures are complex, specialized detectors may substitute for separation efficiency. One specialized detector is the array amperometric detector, which allows selective detection of electrochemically active compounds.23 Electrochemical array detectors are discussed in greater detail in Chapter 5. Many pharmaceutical compounds are chiral, so a detector capable of determining optical purity would be extremely useful in monitoring synthetic reactions. A double-beam circular dichroism detector using a laser as the source was used for the selective detection of chiral cobalt compounds.24 The double-beam, single-source construction reduces the limitations of flicker noise. Chemiluminescence of an ozonized mixture was used as the principle for a sulfur-selective detector used to analyze pesticides, proteins, and blood thiols from rat plasma.25 Chemiluminescence using bis (2,4, 6-trichlorophenyl) oxalate was used for the selective detection of catalytically reduced nitrated polycyclic aromatic hydrocarbons from diesel exhaust.26... 

Based on the described neuroanatomy, the three key matrices for evaluating compound concentrations to determine the extent and/or rate of CNS penetration are blood, CSF, and brain tissue. Due to the nearly universal analysis of plasma to determine systemic concentrations of small molecules, total plasma compound concentration (Cp) will henceforth be substituted for total blood concentration, which is the product of Cp and compound blood-to-plasma ratio. 

Claims have recently been made61 that the dextran of L. mesenteroides may serve as an efficient substitute for blood plasma. Solutions of partially-hydrolyzed dextran in saline gave favorable results when injected intravenously into experimental animals. Preliminary clinical tests were promising. 

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