Use the following passage to answer questions: Hospitals and clinics in the United States and around the world face constant shortages in the supply of blood for transfusions. One alternative currently being explored is to make recombinant human hemoglobin (rHb). In addition to increasing supply for transfusions, rHb has a longer shelf life than red blood cells, is compatible with all blood types, and poses lower risk of transmitting disease. Despite these advantages, neither rHb products nor hemoglobin purified from animals has been licensed as therapy in the United States, mainly because... Show more Use the following passage to answer questions: Hospitals and clinics in the United States and around the world face constant shortages in the supply of blood for transfusions. One alternative currently being explored is to make recombinant human hemoglobin (rHb). In addition to increasing supply for transfusions, rHb has a longer shelf life than red blood cells, is compatible with all blood types, and poses lower risk of transmitting disease. Despite these advantages, neither rHb products nor hemoglobin purified from animals has been licensed as therapy in the United States, mainly because of reports of hypertension and associated cardiovascular and cerebrovascular problems. (A product called HBOC-201, which is purified from cows, has been approved for human use in South Africa and Russia.) The toxicity of rHb has been attributed to the protein's presence in the plasma, where it can scavenge nitric oxide (NO), undergo oxidative reactions that damage tissues, denature, aggregate, and precipitate, among other activities. In contrast, endogenous hemoglobin localizes in erythrocytes, where the cell membrane and cellular reduction pathways reduce or prevent these activities. It has been proposed that the hypertensive effects of rHb could be due to the protein having too low an affinity for oxygen, causing excessive release of oxygen into the arterioles and vasoconstriction. Alternatively, it has been proposed that NO scavenging by rHb from the vasculature leads to depletion of NO, an increase in intracellular calcium, and muscle constriction. Since the 1980s when researchers started studying rHb, various conjugates and amino acid substitutions have been tested for the ability to reduce issues with stability and toxicity. Through mutagenesis strategies, it has been possible to identify rHb variants with different rates of oxygen binding and release, as well as some that are not associated with increases in blood pressure or mean arterial pressure (MAP). However, more work is needed to identify variants with reduced loss of hemin (a protoporphyrin ring containing chelated iron) and globin denaturation. Work is also underway to lower production costs of rHb variants that are being developed as potential therapeutic products. Show less
Use the following passage to answer questions: Hospitals and clinics in the United States and around the world face constant shortages in the supply of blood for transfusions. One alternative currently being explored is to make recombinant human hemoglobin (rHb). In addition to increasing supply for transfusions, rHb has a longer shelf life than red blood cells, is compatible with all blood types, and poses lower risk of transmitting disease. Despite these advantages, neither rHb products nor hemoglobin purified from animals has been licensed as therapy in the United States, mainly because of reports of hypertension and associated cardiovascular and cerebrovascular problems. (A product called HBOC-201, which is purified from cows, has been approved for human use in South Africa and Russia.) The toxicity of rHb has been attributed to the protein's presence in the plasma, where it can scavenge nitric oxide (NO), undergo oxidative reactions that damage tissues, denature, aggregate, and precipitate, among other activities. In contrast, endogenous hemoglobin localizes in erythrocytes, where the cell membrane and cellular reduction pathways reduce or prevent these activities. It has been proposed that the hypertensive effects of rHb could be due to the protein having too low an affinity for oxygen, causing excessive release of oxygen into the arterioles and vasoconstriction. Alternatively, it has been proposed that NO scavenging by rHb from the vasculature leads to depletion of NO, an increase in intracellular calcium, and muscle constriction. Since the 1980s when researchers started studying rHb, various conjugates and amino acid substitutions have been tested for the ability to reduce issues with stability and toxicity. Through mutagenesis strategies, it has been possible to identify rHb variants with different rates of oxygen binding and release, as well as some that are not associated with increases in blood pressure or mean arterial pressure (MAP). However, more work is needed to identify variants with reduced loss of hemin (a protoporphyrin ring containing chelated iron) and globin denaturation. Work is also underway to lower production costs of rHb variants that are being developed as potential therapeutic products.
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