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Published in: Sports Medicine 3/2003

01-03-2003 | Review Article

Drugs for Increasing Oxygen Transport and Their Potential Use in Doping

A Review

Authors: Aurelie Gaudard, Emmanuelle Varlet-Marie, Francoise Bressolle, Michel Audran

Published in: Sports Medicine | Issue 3/2003

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Abstract

Blood oxygenation is a fundamental factor in optimising muscular activity. Enhancement of oxygen delivery to tissues is associated with a substantial improvement in athletic performance, particularly in endurance sports. Progress in medical research has led to the identification of new chemicals for the treatment of severe anaemia. Effective and promising molecules have been created and sometimes used for doping purposes. The aim of this review is to present methods, and drugs, known to be (or that might be) used by athletes to increase oxygen transport in an attempt to improve endurance capacity. These methods and drugs include: (i) blood transfusion; (ii) endogenous stimulation of red blood cell production at altitude, or using hypoxic rooms, erythropoietins (EPOs), EPO gene therapy or EPO mimetics; (iii) allosteric effectors of haemoglobin; and (iv) blood substitutes such as modified haemoglobin solutions and perfluorochemicals. Often, new chemicals are used before safety tests have been completed and athletes are taking great health risks. Such new chemicals have also created the need for new instrumental strategies in doping control laboratories, but not all of these chemicals are detectable. Further progress in analytical research is necessary.
Literature
1.
go back to reference Ekblom B, Berglund B. Effect of erythropoietin administration on maximal aerobic power in man. Scand J Med Sci Sports 1991; 1: 88–93CrossRef Ekblom B, Berglund B. Effect of erythropoietin administration on maximal aerobic power in man. Scand J Med Sci Sports 1991; 1: 88–93CrossRef
2.
go back to reference Vandegriff KD. Haemoglobin-based oxygen carriers. Expert Opin Investig Drugs 2000 Sep; 9(9): 1967–84PubMedCrossRef Vandegriff KD. Haemoglobin-based oxygen carriers. Expert Opin Investig Drugs 2000 Sep; 9(9): 1967–84PubMedCrossRef
3.
go back to reference McCarthy MR, Vandegriff KD, Winslow RM. The role of facilitated diffusion in oxygen transport by cell-free haemoglobins: implications for the design of haemoglobin-based oxygen carriers. Biophys Chem 2001 Aug 30; 92(1–2): 103–7PubMedCrossRef McCarthy MR, Vandegriff KD, Winslow RM. The role of facilitated diffusion in oxygen transport by cell-free haemoglobins: implications for the design of haemoglobin-based oxygen carriers. Biophys Chem 2001 Aug 30; 92(1–2): 103–7PubMedCrossRef
4.
go back to reference Stryer L. Biochemistry. 4th ed. New York: WH Freeman and Company, 1995: 159–60 Stryer L. Biochemistry. 4th ed. New York: WH Freeman and Company, 1995: 159–60
5.
go back to reference Benesch R, Benesch RE. Intracellular organic phosphates as regulators of oxygen release by haemoglobin. Nature 1969 Feb 15; 221(181): 618–22PubMedCrossRef Benesch R, Benesch RE. Intracellular organic phosphates as regulators of oxygen release by haemoglobin. Nature 1969 Feb 15; 221(181): 618–22PubMedCrossRef
6.
go back to reference Benesch R, Benesch RE, Yu CI. Reciprocal binding of oxygen and diphosphoglycerate by human haemoglobin. Proc Natl Acad Sci 1968 Feb; 59: 526–32PubMedCrossRef Benesch R, Benesch RE, Yu CI. Reciprocal binding of oxygen and diphosphoglycerate by human haemoglobin. Proc Natl Acad Sci 1968 Feb; 59: 526–32PubMedCrossRef
7.
go back to reference Ekblom B, Goldbarg AN, Gullbring B. Response to exercise after blood loss and reinfusion of red blood cells. J Appl Physiol 1982; 33: 175–80 Ekblom B, Goldbarg AN, Gullbring B. Response to exercise after blood loss and reinfusion of red blood cells. J Appl Physiol 1982; 33: 175–80
8.
go back to reference Ekblom B, Wilson G, Astrand PO. Central circulation during exercise after venesection and reinfusion of red blood cells. J Appl Physiol 1976; 40: 379–83PubMed Ekblom B, Wilson G, Astrand PO. Central circulation during exercise after venesection and reinfusion of red blood cells. J Appl Physiol 1976; 40: 379–83PubMed
9.
go back to reference Buick FJ, Glehill N, Froese AB, et al. Effect of induced erythrocythaemia on aerobic power capacity. J Appl Physiol 1980; 48: 636–42PubMed Buick FJ, Glehill N, Froese AB, et al. Effect of induced erythrocythaemia on aerobic power capacity. J Appl Physiol 1980; 48: 636–42PubMed
10.
go back to reference Kanstrup IL, Ekblom B. Acute hypervolemia, cardiac performance and aerobic power during exercise. J Appl Physiol 1982; 52: 1186–91PubMed Kanstrup IL, Ekblom B. Acute hypervolemia, cardiac performance and aerobic power during exercise. J Appl Physiol 1982; 52: 1186–91PubMed
11.
go back to reference Gledhill N. The influence of altered blood volume and oxygen-transport capacity on aerobic performance. Exerc Sport Sci Rev 1985; 13: 75–93PubMedCrossRef Gledhill N. The influence of altered blood volume and oxygen-transport capacity on aerobic performance. Exerc Sport Sci Rev 1985; 13: 75–93PubMedCrossRef
12.
go back to reference Berglund B, Hemmingsson P, Birgegard G. Detection of autologous blood transfusions in cross-country skiers. Int J Sports Med 1987; 8: 66–70PubMedCrossRef Berglund B, Hemmingsson P, Birgegard G. Detection of autologous blood transfusions in cross-country skiers. Int J Sports Med 1987; 8: 66–70PubMedCrossRef
13.
go back to reference Ekblom BT. Blood boosting and sport. Baillières Best Pract Res Clin Endocrinol Metab 2000; 14(1): 89–98PubMedCrossRef Ekblom BT. Blood boosting and sport. Baillières Best Pract Res Clin Endocrinol Metab 2000; 14(1): 89–98PubMedCrossRef
14.
go back to reference Gledhill N. Blood doping and related issues: a brief review. Med Sci Sports Exerc 1982; 14: 183–9PubMed Gledhill N. Blood doping and related issues: a brief review. Med Sci Sports Exerc 1982; 14: 183–9PubMed
15.
go back to reference Gledhill N, Warburton D, Jamnick V. Haemoglobin, blood volume, cardiac function, and aerobic power. Can J Appl Physiol 1999; 24: 54–65PubMedCrossRef Gledhill N, Warburton D, Jamnick V. Haemoglobin, blood volume, cardiac function, and aerobic power. Can J Appl Physiol 1999; 24: 54–65PubMedCrossRef
16.
go back to reference Gladwell F, Jopke T. Ethics of blood doping. Phys Sports Med 1985; 13: 145–51 Gladwell F, Jopke T. Ethics of blood doping. Phys Sports Med 1985; 13: 145–51
17.
go back to reference Brien AJ, Simon TL. The effects of red blood cell infusion on 10-km race time. JAMA 1987 May; 257: 2761–5PubMedCrossRef Brien AJ, Simon TL. The effects of red blood cell infusion on 10-km race time. JAMA 1987 May; 257: 2761–5PubMedCrossRef
18.
go back to reference Klein HG. Blood transfusion and athletics games people play. N Engl J Med 1985 Mar; 312(13): 854–6PubMedCrossRef Klein HG. Blood transfusion and athletics games people play. N Engl J Med 1985 Mar; 312(13): 854–6PubMedCrossRef
19.
go back to reference Berglund B. Development of techniques for the detection of blood doping in sports. Sports Med 1988 Feb; 5(2): 127–35PubMedCrossRef Berglund B. Development of techniques for the detection of blood doping in sports. Sports Med 1988 Feb; 5(2): 127–35PubMedCrossRef
20.
go back to reference d’Onofrio G, Zini G. Addendeum to strategies to deter blood doping in sports [letter]. Haematologica 2002; 87(7): ELT31PubMed d’Onofrio G, Zini G. Addendeum to strategies to deter blood doping in sports [letter]. Haematologica 2002; 87(7): ELT31PubMed
21.
go back to reference Jelkmann W, Metzen E. Erythropoietin in the control of red cell production. Ann Anat 1996; 178: 391–403PubMedCrossRef Jelkmann W, Metzen E. Erythropoietin in the control of red cell production. Ann Anat 1996; 178: 391–403PubMedCrossRef
22.
go back to reference Ratcliffe PJ, Ebert BL, Ferguson DJ, et al. Regulation of the erythropoietin gene. Nephrol Dial Transplant 1995; 10Suppl. 2: 18–27PubMedCrossRef Ratcliffe PJ, Ebert BL, Ferguson DJ, et al. Regulation of the erythropoietin gene. Nephrol Dial Transplant 1995; 10Suppl. 2: 18–27PubMedCrossRef
23.
go back to reference Goldberg MA, Dunning SP, Bunn HF. Regulation of the erythropoietin gene: evidence that the oxygen sensor is a heme protein. Science 1998; 242: 1412–5CrossRef Goldberg MA, Dunning SP, Bunn HF. Regulation of the erythropoietin gene: evidence that the oxygen sensor is a heme protein. Science 1998; 242: 1412–5CrossRef
24.
go back to reference Beck I, Weinmann R, Caro J. Characterization of the hypoxia-responsive enhancer in the human erythropoietin shows presence of hypoxia-inducible 120 Kd nuclear DNA-binding protein in erythropoietin-producing and nonproducing cells. Blood 1993; 82: 704–11PubMed Beck I, Weinmann R, Caro J. Characterization of the hypoxia-responsive enhancer in the human erythropoietin shows presence of hypoxia-inducible 120 Kd nuclear DNA-binding protein in erythropoietin-producing and nonproducing cells. Blood 1993; 82: 704–11PubMed
25.
go back to reference Nissenson AR. Novel erythropoiesis stimulating protein for managing the anemia of chronic kidney disease. Am J Kidney Dis 2001 Dec; 38(6): 1390–7PubMedCrossRef Nissenson AR. Novel erythropoiesis stimulating protein for managing the anemia of chronic kidney disease. Am J Kidney Dis 2001 Dec; 38(6): 1390–7PubMedCrossRef
26.
go back to reference Moriya H, Maitani Y, Shimoda N, et al. Pharmacokinetic and pharmacological profiles of free and liposomal recombinant human erythropoietin after intravenous and subcutaneous administrations in rats. Pharm Res 1997; 14(11): 1621–8PubMedCrossRef Moriya H, Maitani Y, Shimoda N, et al. Pharmacokinetic and pharmacological profiles of free and liposomal recombinant human erythropoietin after intravenous and subcutaneous administrations in rats. Pharm Res 1997; 14(11): 1621–8PubMedCrossRef
27.
go back to reference Johnson DL, Jolliffe LK. Erythropoietin mimetic peptides and the future. Nephrol Dial Transplant 2000 Dec; 15(9): 1274–7PubMedCrossRef Johnson DL, Jolliffe LK. Erythropoietin mimetic peptides and the future. Nephrol Dial Transplant 2000 Dec; 15(9): 1274–7PubMedCrossRef
28.
go back to reference Kuai L, Wu C, Qiu Q, et al. Plasminogen activator inhibitor-1 fused with erythropoietin (EPO) mimetic peptide (EMP) enhances the EPO activity of EMP. J Pept Res 2000 Aug; 56(2): 59–62PubMedCrossRef Kuai L, Wu C, Qiu Q, et al. Plasminogen activator inhibitor-1 fused with erythropoietin (EPO) mimetic peptide (EMP) enhances the EPO activity of EMP. J Pept Res 2000 Aug; 56(2): 59–62PubMedCrossRef
29.
go back to reference Middleton SA, Barbone FP, Johnson DL, et al. Shared and unique determinants of the erythropoietin (EPO) receptor are important for binding EPO and EPO mimetic peptide. J Biol Chem 1999 May; 274(20): 14163–9PubMedCrossRef Middleton SA, Barbone FP, Johnson DL, et al. Shared and unique determinants of the erythropoietin (EPO) receptor are important for binding EPO and EPO mimetic peptide. J Biol Chem 1999 May; 274(20): 14163–9PubMedCrossRef
30.
go back to reference Remy I, Wilson IA, Michnick SW. Erythropoietin receptor activation by a ligand-induced conformation change. Science 1999; 283(5404): 990–3PubMedCrossRef Remy I, Wilson IA, Michnick SW. Erythropoietin receptor activation by a ligand-induced conformation change. Science 1999; 283(5404): 990–3PubMedCrossRef
31.
go back to reference Samaja M. Hypoxia-dependent protein expression: erythropoietin. High Alt Med Biol 2001; 2: 155–63PubMedCrossRef Samaja M. Hypoxia-dependent protein expression: erythropoietin. High Alt Med Biol 2001; 2: 155–63PubMedCrossRef
33.
go back to reference Hurtado A. Animals in high altitudes: resident man. Handbook of physiology: adaptation to environment. Washington, DC: American Physiology Society, 1964: 843–60 Hurtado A. Animals in high altitudes: resident man. Handbook of physiology: adaptation to environment. Washington, DC: American Physiology Society, 1964: 843–60
34.
go back to reference Bailey MD, Davies B. Physiological implications of altitude training for endurance performance at sea level: a review. Br J Sports Med 1997 Sep; 31(3): 183–90PubMedCrossRef Bailey MD, Davies B. Physiological implications of altitude training for endurance performance at sea level: a review. Br J Sports Med 1997 Sep; 31(3): 183–90PubMedCrossRef
35.
go back to reference Beall CM, Blangero J, Williams-Blangero S, et al. Major gene for percent of oxygen saturation of arterial haemoglobin in Tibetan highlanders. Am J Phys Anthropol 1994 Nov; 95(3): 271–6PubMedCrossRef Beall CM, Blangero J, Williams-Blangero S, et al. Major gene for percent of oxygen saturation of arterial haemoglobin in Tibetan highlanders. Am J Phys Anthropol 1994 Nov; 95(3): 271–6PubMedCrossRef
36.
go back to reference Boning D, Rojas J, Serrato M, et al. Haemoglobin mass and peak oxygen uptake in untrained and trained residents of moderate altitude. Int J Sports Med 2001; 22: 572–8PubMedCrossRef Boning D, Rojas J, Serrato M, et al. Haemoglobin mass and peak oxygen uptake in untrained and trained residents of moderate altitude. Int J Sports Med 2001; 22: 572–8PubMedCrossRef
37.
go back to reference Ward MP, Milledge JS, West JB. High altitude medicine and physiology. 2nd ed. London: Chapman and Hall Medical, 1995 Ward MP, Milledge JS, West JB. High altitude medicine and physiology. 2nd ed. London: Chapman and Hall Medical, 1995
38.
go back to reference Winslow RM, Monge CC. Hypoxia, polycythemia and chronic mountain sickness. Baltimore (MD): John Hopkins University Press, 1987 Winslow RM, Monge CC. Hypoxia, polycythemia and chronic mountain sickness. Baltimore (MD): John Hopkins University Press, 1987
39.
go back to reference Milledge JS. High altitude. In: Harries M, Williams C, Stabish W, et al., editors. Oxford textbook of sports medicine. London: Oxford University Press, 1994: 217–30 Milledge JS. High altitude. In: Harries M, Williams C, Stabish W, et al., editors. Oxford textbook of sports medicine. London: Oxford University Press, 1994: 217–30
40.
go back to reference Levine BD, Stray-Gundersen J. A practical approach to altitude training: where to live and train for optimal performance enhancement. Int J Sports Med 1992; 13Suppl. 1: S209–12PubMedCrossRef Levine BD, Stray-Gundersen J. A practical approach to altitude training: where to live and train for optimal performance enhancement. Int J Sports Med 1992; 13Suppl. 1: S209–12PubMedCrossRef
41.
go back to reference Stray-Gundersen J, Levine BD. ‘Living high and training low’ can improve sea level performance in endurance athletes. Br J Sports Med 1999 Jun; 33(3): 150–4PubMedCrossRef Stray-Gundersen J, Levine BD. ‘Living high and training low’ can improve sea level performance in endurance athletes. Br J Sports Med 1999 Jun; 33(3): 150–4PubMedCrossRef
42.
go back to reference Levine BD, Stray-Gundersen J, Duhaime G, et al. Living high, training low: the effect of altitude acclimatization/normoxic training in trained runners [abstract]. Med Sci Sports Exerc 1991; 23Suppl. 4: 25S Levine BD, Stray-Gundersen J, Duhaime G, et al. Living high, training low: the effect of altitude acclimatization/normoxic training in trained runners [abstract]. Med Sci Sports Exerc 1991; 23Suppl. 4: 25S
43.
go back to reference Stray-Gundersen J, Chapman RF, Levine BD. ‘Living high-training low’ altitude training improves sea level performance in male and female elite runners. J Appl Physiol 2001; 91: 1113–20PubMed Stray-Gundersen J, Chapman RF, Levine BD. ‘Living high-training low’ altitude training improves sea level performance in male and female elite runners. J Appl Physiol 2001; 91: 1113–20PubMed
44.
go back to reference Geiser J, Vogt M, Billeter R, et al. Training high, living low: changes of aerobic performance and muscle structure with training at simulated altitude. Int J Sports Med 2001 Nov; 22: 579–85PubMedCrossRef Geiser J, Vogt M, Billeter R, et al. Training high, living low: changes of aerobic performance and muscle structure with training at simulated altitude. Int J Sports Med 2001 Nov; 22: 579–85PubMedCrossRef
45.
go back to reference Hoppeler H, Vogt M. Hypoxia training for sea-level performance: training high-living low. Adv Exp Med Biol 2001; 502: 61–73PubMed Hoppeler H, Vogt M. Hypoxia training for sea-level performance: training high-living low. Adv Exp Med Biol 2001; 502: 61–73PubMed
46.
go back to reference Levine BD, Stray-Gundersen J. The effects of altitude training are mediated primarily by acclimatization, rather than by hypoxic exercise. Adv Exp Med Biol 2001; 502: 75–88PubMed Levine BD, Stray-Gundersen J. The effects of altitude training are mediated primarily by acclimatization, rather than by hypoxic exercise. Adv Exp Med Biol 2001; 502: 75–88PubMed
47.
go back to reference Dick FW. Training at altitude in practice. Int J Sports Med 1992 Oct; 13: 203–5CrossRef Dick FW. Training at altitude in practice. Int J Sports Med 1992 Oct; 13: 203–5CrossRef
48.
go back to reference Berglund B. High-altitude training: aspects of haematological adaptation. Sports Med 1992 Nov; 14(5): 289–303PubMedCrossRef Berglund B. High-altitude training: aspects of haematological adaptation. Sports Med 1992 Nov; 14(5): 289–303PubMedCrossRef
49.
go back to reference Rusko HK, Leppavuori A, Makela P, et al. Living high, training low: a new approach to 48 altitude training at sea level in athletes [abstract]. Med Sci Sports Exerc 1995; 27Suppl. 5: 6S Rusko HK, Leppavuori A, Makela P, et al. Living high, training low: a new approach to 48 altitude training at sea level in athletes [abstract]. Med Sci Sports Exerc 1995; 27Suppl. 5: 6S
51.
go back to reference Laitinen H, Alopaeus K, Heikkinen R, et al. Acclimatization to living in normobaric hypoxia and training at sea level in runners [abstract]. Med Sci Sports Exerc 1995; 27Suppl. 5: 109S Laitinen H, Alopaeus K, Heikkinen R, et al. Acclimatization to living in normobaric hypoxia and training at sea level in runners [abstract]. Med Sci Sports Exerc 1995; 27Suppl. 5: 109S
52.
go back to reference Mattila V, Rusko H. Effect of living high and training low on sea level performance in cyclists [abstract]. Med Sci Sports Exerc 1996; 28Suppl. 5: 157S Mattila V, Rusko H. Effect of living high and training low on sea level performance in cyclists [abstract]. Med Sci Sports Exerc 1996; 28Suppl. 5: 157S
53.
go back to reference Piehl-Aulin K, Svedenhag J, Wide L, et al. Short-term intermittent normobaric hypoxia-haematological physiological and mental effect. Scand J Med Sci Sports 1998; 8: 132–7PubMedCrossRef Piehl-Aulin K, Svedenhag J, Wide L, et al. Short-term intermittent normobaric hypoxia-haematological physiological and mental effect. Scand J Med Sci Sports 1998; 8: 132–7PubMedCrossRef
54.
go back to reference Ashenden MJ, Gore CJ, Dobson GP, et al. Simulated moderate altitude elevates serum erythropoietin but does not increase reticulocyte production in well-trained runners. Eur J Appl Physiol 2000; 81: 428–35PubMedCrossRef Ashenden MJ, Gore CJ, Dobson GP, et al. Simulated moderate altitude elevates serum erythropoietin but does not increase reticulocyte production in well-trained runners. Eur J Appl Physiol 2000; 81: 428–35PubMedCrossRef
55.
go back to reference Rodriguez FA, Ventura JL, Casas M, et al. Erythropoietin acute reaction and haematological adaptations to short, intermittent hypobaric hypoxia. Eur J Appl Physiol 2000; 82: 170–7PubMedCrossRef Rodriguez FA, Ventura JL, Casas M, et al. Erythropoietin acute reaction and haematological adaptations to short, intermittent hypobaric hypoxia. Eur J Appl Physiol 2000; 82: 170–7PubMedCrossRef
56.
go back to reference Nummela A. Acclimatization to altitude and normoxic training improve 400m running performance at sea level. J Sports Sci 2000; 18: 411–9PubMedCrossRef Nummela A. Acclimatization to altitude and normoxic training improve 400m running performance at sea level. J Sports Sci 2000; 18: 411–9PubMedCrossRef
57.
go back to reference Ashenden MJ, Gore CJ, Martin DT, et al. Effects of a 12-day ‘live high train low’ camp on reticulocytes production and haemoglobin mass in elite female road cyclists. Eur J Appl Physiol 1999; 80: 472–8CrossRef Ashenden MJ, Gore CJ, Martin DT, et al. Effects of a 12-day ‘live high train low’ camp on reticulocytes production and haemoglobin mass in elite female road cyclists. Eur J Appl Physiol 1999; 80: 472–8CrossRef
58.
go back to reference Ashenden MJ, Gore CJ, Dobson GP, et al. ‘Live high, train low’ does not change the total haemoglobin mass of male endurance athletes sleeping at a simulated altitude of 3000m for 23 nights. Eur J Appl Physiol 1999; 80: 479–84CrossRef Ashenden MJ, Gore CJ, Dobson GP, et al. ‘Live high, train low’ does not change the total haemoglobin mass of male endurance athletes sleeping at a simulated altitude of 3000m for 23 nights. Eur J Appl Physiol 1999; 80: 479–84CrossRef
59.
go back to reference Morris DM, Kearney JT, Burke ER. The effects of breathing supplemental oxygen during altitude training on cycling performance. J Sci Med Sport 2000; 3: 165–75PubMedCrossRef Morris DM, Kearney JT, Burke ER. The effects of breathing supplemental oxygen during altitude training on cycling performance. J Sci Med Sport 2000; 3: 165–75PubMedCrossRef
60.
go back to reference Chick TW, Stark DM, Murata GH. Hyperoxic training increases work capacity after maximal training at moderate altitude. Chest 1993; 104: 1759–62PubMedCrossRef Chick TW, Stark DM, Murata GH. Hyperoxic training increases work capacity after maximal training at moderate altitude. Chest 1993; 104: 1759–62PubMedCrossRef
61.
go back to reference Knaupp W, Khilmani S, Sherwood J, et al. Erythropoietin response to acute normobaric hypoxia in humans. J Appl Physiol 1992; 73: 837–40PubMed Knaupp W, Khilmani S, Sherwood J, et al. Erythropoietin response to acute normobaric hypoxia in humans. J Appl Physiol 1992; 73: 837–40PubMed
62.
go back to reference Frey WO, Zenhausern R, Colombani PC, et al. Influence of intermittent exposure to normobaric hypoxia on hematological indexes and exercise performance [abstract]. Med Sci Sports Exerc 2000; 32Suppl. 5: 65S Frey WO, Zenhausern R, Colombani PC, et al. Influence of intermittent exposure to normobaric hypoxia on hematological indexes and exercise performance [abstract]. Med Sci Sports Exerc 2000; 32Suppl. 5: 65S
63.
go back to reference Terrados N, Melichna J, Sylven C, et al. Effects of training at simulated altitude on performance and muscle metabolic capacity in competitive road cyclists. Eur J Appl Physiol 1988; 57: 203–9CrossRef Terrados N, Melichna J, Sylven C, et al. Effects of training at simulated altitude on performance and muscle metabolic capacity in competitive road cyclists. Eur J Appl Physiol 1988; 57: 203–9CrossRef
64.
go back to reference Meeuwsen T, Hendrksen IJM, Holewijn M, et al. Training-induced increases in sea-level performance is enhanced by acute intermittent hypobaric hypoxia: a 2 year crossover study [abstract]. Med Sci Sports Exerc 2000; 32Suppl. 5: 251S Meeuwsen T, Hendrksen IJM, Holewijn M, et al. Training-induced increases in sea-level performance is enhanced by acute intermittent hypobaric hypoxia: a 2 year crossover study [abstract]. Med Sci Sports Exerc 2000; 32Suppl. 5: 251S
65.
go back to reference Berglund B, Gennser M, Ornhagen H, et al. Erythropoietin concentrations during 10 days of normobaric hypoxia under controlled environmental circumstances. Acta Physiol Scand 2002 Mar; 174(3): 225–9PubMedCrossRef Berglund B, Gennser M, Ornhagen H, et al. Erythropoietin concentrations during 10 days of normobaric hypoxia under controlled environmental circumstances. Acta Physiol Scand 2002 Mar; 174(3): 225–9PubMedCrossRef
66.
go back to reference Jacobson LO, Goldwasser E, Fried W, et al. Role of the kidney in erythropoiesis. Nature 1957; 179: 633–4PubMedCrossRef Jacobson LO, Goldwasser E, Fried W, et al. Role of the kidney in erythropoiesis. Nature 1957; 179: 633–4PubMedCrossRef
67.
go back to reference Fried W. The liver as a source of extrarenal erythropoietin production. Blood 1972; 40: 671–7PubMed Fried W. The liver as a source of extrarenal erythropoietin production. Blood 1972; 40: 671–7PubMed
68.
go back to reference Fisher JW. Extrarenal erythropoietin production. J Lab Clin Med 1979; 93: 695–9PubMed Fisher JW. Extrarenal erythropoietin production. J Lab Clin Med 1979; 93: 695–9PubMed
69.
go back to reference Braumann KM, Nonnast-Daniel B, Boning D, et al. Improved physical performance after treatment of renal anaemia with recombinant human erythropoietin. Nephron 1991; 58: 129–34PubMedCrossRef Braumann KM, Nonnast-Daniel B, Boning D, et al. Improved physical performance after treatment of renal anaemia with recombinant human erythropoietin. Nephron 1991; 58: 129–34PubMedCrossRef
70.
go back to reference Horina JH, Schwaverger G, Brassee H, et al. Increased red cell 2,3-diphosphoglycerate levels in haemodialysis patients treated with erythropoietin. Nephrol Dial Transplant 1993; 8: 1219–22PubMed Horina JH, Schwaverger G, Brassee H, et al. Increased red cell 2,3-diphosphoglycerate levels in haemodialysis patients treated with erythropoietin. Nephrol Dial Transplant 1993; 8: 1219–22PubMed
71.
go back to reference Grunze M, Kohlmann M, Mulligan M, et al. Mechanisms of improved physical performance of chronic haemodialysis patients after erythropoietin treatment. Am J Nephrol 1990; 10Suppl. 2: 15–8PubMedCrossRef Grunze M, Kohlmann M, Mulligan M, et al. Mechanisms of improved physical performance of chronic haemodialysis patients after erythropoietin treatment. Am J Nephrol 1990; 10Suppl. 2: 15–8PubMedCrossRef
72.
go back to reference Raine AE. Hypertension, blood viscosity, and cardiovascular morbidity in renal failure: implications of erythropoietin therapy. Lancet 1988 Jan 16; I(8577): 97–100CrossRef Raine AE. Hypertension, blood viscosity, and cardiovascular morbidity in renal failure: implications of erythropoietin therapy. Lancet 1988 Jan 16; I(8577): 97–100CrossRef
73.
go back to reference Piron M, Loo M, Gothot A, et al. Cessation of intensive treatment with recombinant human erythropoietin is followed by secondary anemia. Blood 2001 Jan 15; 97(2): 442–8PubMedCrossRef Piron M, Loo M, Gothot A, et al. Cessation of intensive treatment with recombinant human erythropoietin is followed by secondary anemia. Blood 2001 Jan 15; 97(2): 442–8PubMedCrossRef
74.
go back to reference Casadevall N, Nataf J, Viron B, et al. Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin. N Engl J Med 2002 Feb 14; 346(7): 469–75PubMedCrossRef Casadevall N, Nataf J, Viron B, et al. Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin. N Engl J Med 2002 Feb 14; 346(7): 469–75PubMedCrossRef
75.
go back to reference Wide L, Bengtsson C, Berglund B, et al. Detection in blood and urine of recombinant erythropoietin administered to healthy men. Med Sci Sports Exerc 1995; 27: 1569–76PubMed Wide L, Bengtsson C, Berglund B, et al. Detection in blood and urine of recombinant erythropoietin administered to healthy men. Med Sci Sports Exerc 1995; 27: 1569–76PubMed
76.
go back to reference Wilber RL. Detection of DNA-recombinant human epoetin-alfa as a pharmacological ergogenic aid. Sports Med 2002; 32(2): 125–42PubMedCrossRef Wilber RL. Detection of DNA-recombinant human epoetin-alfa as a pharmacological ergogenic aid. Sports Med 2002; 32(2): 125–42PubMedCrossRef
77.
go back to reference Parisotto R, Gore CJ, Emslie KR, et al. A novel method utilising markers of altered erythropoiesis for the detection of recombinant human erythropoietin abuse in athletes. Haemato-logica 2000; 85: 564–72 Parisotto R, Gore CJ, Emslie KR, et al. A novel method utilising markers of altered erythropoiesis for the detection of recombinant human erythropoietin abuse in athletes. Haemato-logica 2000; 85: 564–72
78.
go back to reference Parisotto R, Wu M, Ashenden MJ, et al. Detection of recombinant human erythropoietin abuse in athletes utilizing markers of altered erythropoiesis. Haematologica 2001 Feb; 86(2): 128–37PubMed Parisotto R, Wu M, Ashenden MJ, et al. Detection of recombinant human erythropoietin abuse in athletes utilizing markers of altered erythropoiesis. Haematologica 2001 Feb; 86(2): 128–37PubMed
79.
go back to reference Lasne F. Double-blotting: a solution to the problem of nonspecific binding of secondary antibodies in immunoblotting procedures. J Immunol Methods 2001 Jul 1; 253(1–2): 125–31PubMedCrossRef Lasne F. Double-blotting: a solution to the problem of nonspecific binding of secondary antibodies in immunoblotting procedures. J Immunol Methods 2001 Jul 1; 253(1–2): 125–31PubMedCrossRef
80.
go back to reference Bren A, Kandus A, Varl J, et al. A comparison between epoetin omega and epoetin alfa in the correction of anemia in hemodialysis patients: a prospective, controlled crossover study. Artif Organs 2002 Feb; 26(2): 91–7PubMedCrossRef Bren A, Kandus A, Varl J, et al. A comparison between epoetin omega and epoetin alfa in the correction of anemia in hemodialysis patients: a prospective, controlled crossover study. Artif Organs 2002 Feb; 26(2): 91–7PubMedCrossRef
81.
go back to reference Sikole A, Spasovski G, Zafirov D, et al. Epoetin omega for treatment of anaemia in maintenance hemodialysis patients. Clin Nephrol 2002 Mar; 57(3): 237–45PubMed Sikole A, Spasovski G, Zafirov D, et al. Epoetin omega for treatment of anaemia in maintenance hemodialysis patients. Clin Nephrol 2002 Mar; 57(3): 237–45PubMed
82.
go back to reference Egrie JC, Grant JR, Gillies DK, et al. The role of carbohydrate on the biological activity of erythropoietin [abstract]. Glycoconj J 1993; 10: 263CrossRef Egrie JC, Grant JR, Gillies DK, et al. The role of carbohydrate on the biological activity of erythropoietin [abstract]. Glycoconj J 1993; 10: 263CrossRef
83.
go back to reference Dordal MS, Wang FF, Goldwasser E. The role of carbohydrate in erythropoietin action. Endocrinology 1985; 116: 2293–9PubMedCrossRef Dordal MS, Wang FF, Goldwasser E. The role of carbohydrate in erythropoietin action. Endocrinology 1985; 116: 2293–9PubMedCrossRef
84.
go back to reference Egrie JC, Browne JK. Development and characterization of novel erythropoiesis stimulating protein (NESP). Nephrol Dial Transplant 2001; 16 (3 Suppl.): 3–13PubMedCrossRef Egrie JC, Browne JK. Development and characterization of novel erythropoiesis stimulating protein (NESP). Nephrol Dial Transplant 2001; 16 (3 Suppl.): 3–13PubMedCrossRef
85.
86.
go back to reference Macdougall IC, Gray SJ, Elston O, et al. Pharmacokinetics of novel erythropoiesis stimulating protein compared with epoetin alfa in dialysis patients. J Am Soc Nephrol 1999; 10: 2392–5PubMed Macdougall IC, Gray SJ, Elston O, et al. Pharmacokinetics of novel erythropoiesis stimulating protein compared with epoetin alfa in dialysis patients. J Am Soc Nephrol 1999; 10: 2392–5PubMed
87.
go back to reference Korbett SM. Anemia and erythropoietin in hemodialysis and continuous ambulatory peritoneal dialysis. Kidney Int 1993; 43: 111–9 Korbett SM. Anemia and erythropoietin in hemodialysis and continuous ambulatory peritoneal dialysis. Kidney Int 1993; 43: 111–9
88.
go back to reference Vanrenterghem Y, Barany P, Mann J, et al. Novel erythropoiesis stimulating protein (NESP) maintains haemoglobin (Hgb) in ESRD patients with administered once weekly or once every other week [abstract]. J Am Soc Nephrol 1999; 10: 1365A Vanrenterghem Y, Barany P, Mann J, et al. Novel erythropoiesis stimulating protein (NESP) maintains haemoglobin (Hgb) in ESRD patients with administered once weekly or once every other week [abstract]. J Am Soc Nephrol 1999; 10: 1365A
89.
go back to reference Coyne D, Ling ND, Toto R, et al. Novel erythropoiesis stimulating protein (NESP) corrects anemia in dialysis patients when administered at a reduced dose frequency compared with recombinant-human erythropoietin (r-HuEpo) [abstract]. J Am Soc Nephrol 2000; 11: 1380A Coyne D, Ling ND, Toto R, et al. Novel erythropoiesis stimulating protein (NESP) corrects anemia in dialysis patients when administered at a reduced dose frequency compared with recombinant-human erythropoietin (r-HuEpo) [abstract]. J Am Soc Nephrol 2000; 11: 1380A
90.
go back to reference Graf H, Lacombe JL, Braun J, et al. Novel erythropoiesis stimulating protein (NESP) effectively maintains haemoglobin (Hgb) when administered at a reduced dose frequency compared with recombinant-human erythropoietin (r-HuEpo) in dialysis patients [abstract]. J Am Soc Nephrol 2000; 11: 1317A Graf H, Lacombe JL, Braun J, et al. Novel erythropoiesis stimulating protein (NESP) effectively maintains haemoglobin (Hgb) when administered at a reduced dose frequency compared with recombinant-human erythropoietin (r-HuEpo) in dialysis patients [abstract]. J Am Soc Nephrol 2000; 11: 1317A
91.
go back to reference Amgen Inc. Aranesp® physician package insert. California: 2001 Amgen Inc. Aranesp® physician package insert. California: 2001
92.
go back to reference Macdougall IC. An overview of the efficacy and safety of novel erythropoiesis stimulating protein (NESP). Nephrol Dial Transplant 2001; 16Suppl. 3: 14–21PubMedCrossRef Macdougall IC. An overview of the efficacy and safety of novel erythropoiesis stimulating protein (NESP). Nephrol Dial Transplant 2001; 16Suppl. 3: 14–21PubMedCrossRef
95.
go back to reference Kedar E, Rutkowski Y, Braun E, et al. Delivery of cytokines by liposomes: I, preparation and characterization of interleukin-2 encapsulated in long-circulating sterically stabilized liposomes. J Immunother Emphasis Tumor Immunol 1994; 16: 47–59PubMedCrossRef Kedar E, Rutkowski Y, Braun E, et al. Delivery of cytokines by liposomes: I, preparation and characterization of interleukin-2 encapsulated in long-circulating sterically stabilized liposomes. J Immunother Emphasis Tumor Immunol 1994; 16: 47–59PubMedCrossRef
96.
go back to reference Qi XR, Maitani Y, Shimoda N, et al. Evaluation of liposomal erythropoietin prepared with reverse-phase evaporation vesicle method by subcutaneous administration in rats. Chem Pharm Bull (Tokyo) 1995; 43(2): 295–9CrossRef Qi XR, Maitani Y, Shimoda N, et al. Evaluation of liposomal erythropoietin prepared with reverse-phase evaporation vesicle method by subcutaneous administration in rats. Chem Pharm Bull (Tokyo) 1995; 43(2): 295–9CrossRef
97.
go back to reference Maitani Y, Hazama M, Tojo Y, et al. Oral administration of recombinant human erythropoietin in liposomes in rats: influence of lipid composition and size of liposomes on bioavailability. J Pharm Sci 1996 Apr; 85: 440–5PubMedCrossRef Maitani Y, Hazama M, Tojo Y, et al. Oral administration of recombinant human erythropoietin in liposomes in rats: influence of lipid composition and size of liposomes on bioavailability. J Pharm Sci 1996 Apr; 85: 440–5PubMedCrossRef
98.
go back to reference Maitani Y, Moriya H, Shimoda N, et al. Distribution characteristics of entrapped recombinant human erythropoietin in liposomes and its intestinal absorption in rats. Int J Pharm 1999 Aug; 185: 13–22PubMedCrossRef Maitani Y, Moriya H, Shimoda N, et al. Distribution characteristics of entrapped recombinant human erythropoietin in liposomes and its intestinal absorption in rats. Int J Pharm 1999 Aug; 185: 13–22PubMedCrossRef
99.
go back to reference Regulier E, Schneider BL, Deglon N, et al. Continuous delivery of human and mouse erythropoietin in mice by genetically engineered polymer encapsulated myoblasts. Gene Ther 1998 Aug; 5(8): 1014–22PubMedCrossRef Regulier E, Schneider BL, Deglon N, et al. Continuous delivery of human and mouse erythropoietin in mice by genetically engineered polymer encapsulated myoblasts. Gene Ther 1998 Aug; 5(8): 1014–22PubMedCrossRef
100.
go back to reference Dalle B, Payen E, Regulier R, et al. Improvement of mouse-thalassemia upon erythropoietin delivery by encapsulated myoblasts. Gene Ther 1999 Feb; 6(2): 157–61PubMedCrossRef Dalle B, Payen E, Regulier R, et al. Improvement of mouse-thalassemia upon erythropoietin delivery by encapsulated myoblasts. Gene Ther 1999 Feb; 6(2): 157–61PubMedCrossRef
101.
go back to reference Serguera C, Bohl D, Rolland E, et al. Control of erythropoietin secretion by doxycycline or mifeprostone in mice bearing polymer-encapsulated engineered cell. Hum Gene Ther 1999; 10(3): 375–83PubMedCrossRef Serguera C, Bohl D, Rolland E, et al. Control of erythropoietin secretion by doxycycline or mifeprostone in mice bearing polymer-encapsulated engineered cell. Hum Gene Ther 1999; 10(3): 375–83PubMedCrossRef
103.
go back to reference Kessler P, Podsakoff G, Chen X, et al. Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein. Proc Natl Acad Sci U S A 1996 Nov; 93: 14082–7PubMedCrossRef Kessler P, Podsakoff G, Chen X, et al. Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein. Proc Natl Acad Sci U S A 1996 Nov; 93: 14082–7PubMedCrossRef
104.
go back to reference Zhou S, Murphy JE, Escobedo JA, et al. Adeno-associated virus-mediated delivery of erythropoietin leads to sustained elevation of hematocrit in nonhuman primates. Gene Ther 1998; 5: 665–70PubMedCrossRef Zhou S, Murphy JE, Escobedo JA, et al. Adeno-associated virus-mediated delivery of erythropoietin leads to sustained elevation of hematocrit in nonhuman primates. Gene Ther 1998; 5: 665–70PubMedCrossRef
105.
go back to reference Osborne WRA, Ramesh N, Lau S, et al. Gene therapy for long-term expression of erythropoietin in rats. Proc Natl Acad Sci USA 1995; 92: 8055–8PubMedCrossRef Osborne WRA, Ramesh N, Lau S, et al. Gene therapy for long-term expression of erythropoietin in rats. Proc Natl Acad Sci USA 1995; 92: 8055–8PubMedCrossRef
106.
go back to reference Bohl D, Naffakh N, Heard JM. Long term control of erythropoietin secretion levels by tetracycline in mice transplanted with engineered primary myoblasts. Nat Med 1997; 3: 299–312PubMedCrossRef Bohl D, Naffakh N, Heard JM. Long term control of erythropoietin secretion levels by tetracycline in mice transplanted with engineered primary myoblasts. Nat Med 1997; 3: 299–312PubMedCrossRef
107.
go back to reference Rinsch C, Regulier E, Deglon N, et al. A gene therapy approach to regulated delivery of erythropoietin as a function of oxygen tension. Hum Gene Ther 1997 Nov 1; 8(16): 1881–9PubMedCrossRef Rinsch C, Regulier E, Deglon N, et al. A gene therapy approach to regulated delivery of erythropoietin as a function of oxygen tension. Hum Gene Ther 1997 Nov 1; 8(16): 1881–9PubMedCrossRef
108.
go back to reference Bohl D, Salvetti A, Moullier PH, et al. Control of erythropoietin delivery by doxycycline in mice after intramuscular injection of adeno-associated vector. Blood 1998; 92: 1512–7PubMed Bohl D, Salvetti A, Moullier PH, et al. Control of erythropoietin delivery by doxycycline in mice after intramuscular injection of adeno-associated vector. Blood 1998; 92: 1512–7PubMed
109.
110.
go back to reference Ye X, Rivera VM, Zoltick P, et al. Regulated delivery of therapeutic proteins after in vivo somatic cell gene transfer. Science 1999 Jan 1; 283(5398): 88–91PubMedCrossRef Ye X, Rivera VM, Zoltick P, et al. Regulated delivery of therapeutic proteins after in vivo somatic cell gene transfer. Science 1999 Jan 1; 283(5398): 88–91PubMedCrossRef
111.
go back to reference Abruzzese RV, Godin D, Mehta V, et al. Ligand-dependent regulation of vascular endothelial growth factor and erythropoietin expression by a plasmid-based autoinducible GeneS-witch system. Mol Ther 2000; 2: 276–87PubMedCrossRef Abruzzese RV, Godin D, Mehta V, et al. Ligand-dependent regulation of vascular endothelial growth factor and erythropoietin expression by a plasmid-based autoinducible GeneS-witch system. Mol Ther 2000; 2: 276–87PubMedCrossRef
112.
go back to reference Adam D. Gene therapy may be up to speed for cheats at 2008 Olympics. Nature 2001 Dec 6; 414: 569–70PubMedCrossRef Adam D. Gene therapy may be up to speed for cheats at 2008 Olympics. Nature 2001 Dec 6; 414: 569–70PubMedCrossRef
113.
go back to reference Friedmann T, Koss JO. Gene transfer and athletics: an impending problem. Mol Ther 2001 Jun; 3(6): 819–20PubMedCrossRef Friedmann T, Koss JO. Gene transfer and athletics: an impending problem. Mol Ther 2001 Jun; 3(6): 819–20PubMedCrossRef
114.
go back to reference Sommer B, Rinsch C, Payen E, et al. Long-term doxycycline-regulated secretion of erythropoietin by encapsulated myoblasts. Mol Ther 2002 Aug; 6(2): 155–61PubMedCrossRef Sommer B, Rinsch C, Payen E, et al. Long-term doxycycline-regulated secretion of erythropoietin by encapsulated myoblasts. Mol Ther 2002 Aug; 6(2): 155–61PubMedCrossRef
116.
go back to reference Jolliffe LK, Middleton SA, Barbone FB, et al. Erythropoietin receptor: application in drug development. Nephrol Dial Transplant 1995; 10Suppl. 2: 80–4 Jolliffe LK, Middleton SA, Barbone FB, et al. Erythropoietin receptor: application in drug development. Nephrol Dial Transplant 1995; 10Suppl. 2: 80–4
117.
go back to reference Boulay JL, Paul WE. Haematopoietin sub-family classification based on size, gene organization and sequence homology. Curr Biol 1993; 3: 573–81PubMedCrossRef Boulay JL, Paul WE. Haematopoietin sub-family classification based on size, gene organization and sequence homology. Curr Biol 1993; 3: 573–81PubMedCrossRef
118.
go back to reference Bazan JF. Structural design and molecular evaluation of a cytokine receptor superfamily. Proc Natl Acad Sci U S A 1990; 87: 6934–8PubMedCrossRef Bazan JF. Structural design and molecular evaluation of a cytokine receptor superfamily. Proc Natl Acad Sci U S A 1990; 87: 6934–8PubMedCrossRef
119.
go back to reference Darnell JE, Kerr IA, Starck GR. Jak-STAT pathways and transcriptional activation in response to IFNa and other extracellular signalling proteins. Science 1994; 264: 383–6CrossRef Darnell JE, Kerr IA, Starck GR. Jak-STAT pathways and transcriptional activation in response to IFNa and other extracellular signalling proteins. Science 1994; 264: 383–6CrossRef
121.
go back to reference Wrighton NC, Farrell FX, Chang R, et al. Small peptides as potent mimetics of the protein hormone erythropoietin. Science 1996; 273: 458–63PubMedCrossRef Wrighton NC, Farrell FX, Chang R, et al. Small peptides as potent mimetics of the protein hormone erythropoietin. Science 1996; 273: 458–63PubMedCrossRef
122.
go back to reference Livnah O, Stura EA, Johnson DL, et al. Functional mimicry of a protein hormone by a peptide agonist: the Epo receptor complex at 2.8 Å. Science 1996; 273: 464–71PubMedCrossRef Livnah O, Stura EA, Johnson DL, et al. Functional mimicry of a protein hormone by a peptide agonist: the Epo receptor complex at 2.8 Å. Science 1996; 273: 464–71PubMedCrossRef
123.
go back to reference Constantinescu SN, Ghaffari S, Lodish HF. The erythropoietin receptor: structure, activation and intracellular signal transduction. Trends Endocrinol Metab 1999; 10(1): 18–23PubMedCrossRef Constantinescu SN, Ghaffari S, Lodish HF. The erythropoietin receptor: structure, activation and intracellular signal transduction. Trends Endocrinol Metab 1999; 10(1): 18–23PubMedCrossRef
124.
go back to reference Caravella JA, Lyne PD, Richards WG. A partial model of the erythropoietin receptor complex. Proteins 1996; 24: 394–401PubMedCrossRef Caravella JA, Lyne PD, Richards WG. A partial model of the erythropoietin receptor complex. Proteins 1996; 24: 394–401PubMedCrossRef
125.
go back to reference Barbone FP, Middleton SA, Johnson DL, et al. Mutagenesis studies of the human erythropoietin receptor. J Biol Chem 1997; 272(8): 4985–92PubMedCrossRef Barbone FP, Middleton SA, Johnson DL, et al. Mutagenesis studies of the human erythropoietin receptor. J Biol Chem 1997; 272(8): 4985–92PubMedCrossRef
126.
go back to reference Wrighton NC, Balasubramanian P, Barbone FP, et al. Increased potency of an erythropoietin peptide mimetic through covalent dimerization. Nat Biotech 1997; 15: 1261–5CrossRef Wrighton NC, Balasubramanian P, Barbone FP, et al. Increased potency of an erythropoietin peptide mimetic through covalent dimerization. Nat Biotech 1997; 15: 1261–5CrossRef
127.
go back to reference Livnah O, Johnson DL, Stura EA, et al. An antagonist peptide-Epo receptor complex suggests that receptor dimerization is not sufficient for activation. Nat Struct Biol 1998; 5: 993–1003PubMedCrossRef Livnah O, Johnson DL, Stura EA, et al. An antagonist peptide-Epo receptor complex suggests that receptor dimerization is not sufficient for activation. Nat Struct Biol 1998; 5: 993–1003PubMedCrossRef
129.
go back to reference Johnson DL, Farrell FX, Barbone FP, et al. Amino terminal dimerization of an erythropoietin mimetic peptide results in increased erythropoietic activity. Chem Biol 1997; 4: 939–50PubMedCrossRef Johnson DL, Farrell FX, Barbone FP, et al. Amino terminal dimerization of an erythropoietin mimetic peptide results in increased erythropoietic activity. Chem Biol 1997; 4: 939–50PubMedCrossRef
130.
go back to reference McConnell SJ, Dinh T, Le MH, et al. Isolation of erythropoietin receptor agonist peptides using evolved phage libraries. Biol Chem 1998; 379: 1279–86PubMedCrossRef McConnell SJ, Dinh T, Le MH, et al. Isolation of erythropoietin receptor agonist peptides using evolved phage libraries. Biol Chem 1998; 379: 1279–86PubMedCrossRef
131.
go back to reference Naranda T, Wong K, Kaufman RI, et al. Activation of erythropoietin receptor in the absence of hormone by a peptide that binds to a domain different from the hormone binding site. Proc Natl Acad Sci U S A 1999; 96: 7569–74PubMedCrossRef Naranda T, Wong K, Kaufman RI, et al. Activation of erythropoietin receptor in the absence of hormone by a peptide that binds to a domain different from the hormone binding site. Proc Natl Acad Sci U S A 1999; 96: 7569–74PubMedCrossRef
132.
go back to reference Elliot S, Lorenzini T, Yanaghira D, et al. Activation of the erythropoietin (EPO) receptor by bivalent t anti-Epo receptor antibodies. J Biol Chem 1996; 271: 24691–7CrossRef Elliot S, Lorenzini T, Yanaghira D, et al. Activation of the erythropoietin (EPO) receptor by bivalent t anti-Epo receptor antibodies. J Biol Chem 1996; 271: 24691–7CrossRef
133.
go back to reference Schneider H, Chaovapong W, Matthews DJ, et al. Homodimerization of erythropoietin receptor by bivalent monoclonal antibody triggers cell proliferation and differentiation of erythroid precursors. Blood 1997 Jan; 89(2): 473–82PubMed Schneider H, Chaovapong W, Matthews DJ, et al. Homodimerization of erythropoietin receptor by bivalent monoclonal antibody triggers cell proliferation and differentiation of erythroid precursors. Blood 1997 Jan; 89(2): 473–82PubMed
134.
go back to reference Yoshimura A, Longmore G, Lodish HF. Point mutation in the exoplasmic domain of the erythropoietin receptor resulting in hormone-independent activation and tumorigenicity. Nature 1994; 348: 647–9CrossRef Yoshimura A, Longmore G, Lodish HF. Point mutation in the exoplasmic domain of the erythropoietin receptor resulting in hormone-independent activation and tumorigenicity. Nature 1994; 348: 647–9CrossRef
135.
go back to reference Watowich Y, Yoshimura A, Longmore GD, et al. Homodimerization and constitutive activation of the erythropoietin receptor. Proc Natl Acad Sci U S A 1992; 89: 2140–5PubMedCrossRef Watowich Y, Yoshimura A, Longmore GD, et al. Homodimerization and constitutive activation of the erythropoietin receptor. Proc Natl Acad Sci U S A 1992; 89: 2140–5PubMedCrossRef
136.
go back to reference Watowich Y, Hilton DS, Lodish HF. Activation and inhibition of erythropoietin receptor function: role of receptor dimerization. Mol Cell Biol 1994; 14: 3535–49PubMed Watowich Y, Hilton DS, Lodish HF. Activation and inhibition of erythropoietin receptor function: role of receptor dimerization. Mol Cell Biol 1994; 14: 3535–49PubMed
137.
go back to reference Li JP, D’Andrea AD, Lodish HF, et al. Activation of cell growth by binding of Friend Spleen focus forming gp55 glycoprotein to the erythropoietin receptor. Nature 1990; 343: 762–4PubMedCrossRef Li JP, D’Andrea AD, Lodish HF, et al. Activation of cell growth by binding of Friend Spleen focus forming gp55 glycoprotein to the erythropoietin receptor. Nature 1990; 343: 762–4PubMedCrossRef
138.
go back to reference Qureshi SA, Kim RM, Konteatis Z, et al. Mimicry of erythropoietin by a nonpeptide molecule. Proc Natl Acad Sci U S A 1999; 96(21): 12156–61PubMedCrossRef Qureshi SA, Kim RM, Konteatis Z, et al. Mimicry of erythropoietin by a nonpeptide molecule. Proc Natl Acad Sci U S A 1999; 96(21): 12156–61PubMedCrossRef
139.
go back to reference Navia MA, Chatturvedi PR. Design principles for orally bioavailable drugs. Drug Disc Today 1996; 1: 179–89CrossRef Navia MA, Chatturvedi PR. Design principles for orally bioavailable drugs. Drug Disc Today 1996; 1: 179–89CrossRef
140.
go back to reference Barbone FP, Johnson DL, Farrell FX, et al. New epoietin molecules and novel therapeutic approaches. Nephrol Dial Transplant 1999; 14(2): 80–4PubMedCrossRef Barbone FP, Johnson DL, Farrell FX, et al. New epoietin molecules and novel therapeutic approaches. Nephrol Dial Transplant 1999; 14(2): 80–4PubMedCrossRef
141.
go back to reference Abraham DJ, Wireko FC, Randad RS, et al. Allosteric modifiers of hemoglobin: 2-[4-[(3,5-Disubstituted anilino)carbonyl]-methylphenoxy]-2-methylpropionic acid derivatives that lower whole blood, and in vivo in rats. Biochemistry 1992; 31: 9141–9PubMedCrossRef Abraham DJ, Wireko FC, Randad RS, et al. Allosteric modifiers of hemoglobin: 2-[4-[(3,5-Disubstituted anilino)carbonyl]-methylphenoxy]-2-methylpropionic acid derivatives that lower whole blood, and in vivo in rats. Biochemistry 1992; 31: 9141–9PubMedCrossRef
142.
go back to reference Perutz MF, Poyart C. Bezafibrate lowers oxygen affinity of haemoglobin. Lancet 1983; II: 881–2CrossRef Perutz MF, Poyart C. Bezafibrate lowers oxygen affinity of haemoglobin. Lancet 1983; II: 881–2CrossRef
143.
go back to reference Lalezeri I, Rahbar S, Lalezeri P, et al. LR16, a compound with potent effects on the oxygen affinity of haemoglobin on blood cholesterol and on low density lipoprotein. Proc Natl Acad Sci U S A 1988 Aug; 85: 6117–21CrossRef Lalezeri I, Rahbar S, Lalezeri P, et al. LR16, a compound with potent effects on the oxygen affinity of haemoglobin on blood cholesterol and on low density lipoprotein. Proc Natl Acad Sci U S A 1988 Aug; 85: 6117–21CrossRef
144.
go back to reference Lalezari I, Lalezari P, Poyart C, et al. New effectors of human hemoglobin: structure and function. Biochemistry 1990 Feb; 29: 1515–23PubMedCrossRef Lalezari I, Lalezari P, Poyart C, et al. New effectors of human hemoglobin: structure and function. Biochemistry 1990 Feb; 29: 1515–23PubMedCrossRef
145.
go back to reference Randad RS, Mahran MA, Mehanna AS, et al. Allosteric modifiers of haemoglobin design, synthesis, testing and structure-allosteric activity relationship of novel haemoglobin oxygen affinity decreasing agents. J Med Chem 1991; 34: 752–7PubMedCrossRef Randad RS, Mahran MA, Mehanna AS, et al. Allosteric modifiers of haemoglobin design, synthesis, testing and structure-allosteric activity relationship of novel haemoglobin oxygen affinity decreasing agents. J Med Chem 1991; 34: 752–7PubMedCrossRef
146.
go back to reference Uchida K, Reilly MP, Abraham DJ, et al. Effect of an allosteric modifier of haemoglobin, RSR-4, on oxygen affinity and oxygen saturation of haemoglobin in rabbits. Jpn J Physiol 1998; 48: 439–44PubMedCrossRef Uchida K, Reilly MP, Abraham DJ, et al. Effect of an allosteric modifier of haemoglobin, RSR-4, on oxygen affinity and oxygen saturation of haemoglobin in rabbits. Jpn J Physiol 1998; 48: 439–44PubMedCrossRef
147.
go back to reference Wahr JA, Gerber M, Venitz J, et al. Allosteric modification of oxygen delivery by haemoglobin. Anesth Analg 2001; 92: 615–20PubMedCrossRef Wahr JA, Gerber M, Venitz J, et al. Allosteric modification of oxygen delivery by haemoglobin. Anesth Analg 2001; 92: 615–20PubMedCrossRef
148.
go back to reference Kleinberg L, Grossman SA, Piantadosi S, et al. Phase I trial to determine the safety, pharmacodynamics, and pharmacokinetics of RSR13, a novel radioenhancer, in newly diagnosed glioblastoma multiforme. J Clin Oncol 1999; 17(8): 2593–603PubMed Kleinberg L, Grossman SA, Piantadosi S, et al. Phase I trial to determine the safety, pharmacodynamics, and pharmacokinetics of RSR13, a novel radioenhancer, in newly diagnosed glioblastoma multiforme. J Clin Oncol 1999; 17(8): 2593–603PubMed
149.
go back to reference Eichelbronner O, Sielenkamper A, D’Almeida M, et al. Effects of FI (O (2)) on hemodynamic responses and O (2) transport during RSR13-induced reduction in P (50). Am J Physiol 1999 Jul; 277 (1 Pt 2): 290H–8H Eichelbronner O, Sielenkamper A, D’Almeida M, et al. Effects of FI (O (2)) on hemodynamic responses and O (2) transport during RSR13-induced reduction in P (50). Am J Physiol 1999 Jul; 277 (1 Pt 2): 290H–8H
150.
go back to reference Phelps Grella M, Danso-Danquah R, Safo MK, et al. Synthesis and structure-activity relationships of chiral allosteric modifiers of hemoglobin. J Med Chem 2000; 43: 4726–37PubMedCrossRef Phelps Grella M, Danso-Danquah R, Safo MK, et al. Synthesis and structure-activity relationships of chiral allosteric modifiers of hemoglobin. J Med Chem 2000; 43: 4726–37PubMedCrossRef
151.
go back to reference Youssef AM, Safo KM, Danso-Danquah R, et al. Synthesis and X-ray studies of chiral allosteric modifiers of hemoglobin. J Med Chem 2002; 45: 1184–95PubMedCrossRef Youssef AM, Safo KM, Danso-Danquah R, et al. Synthesis and X-ray studies of chiral allosteric modifiers of hemoglobin. J Med Chem 2002; 45: 1184–95PubMedCrossRef
152.
go back to reference Breidbach A, Catlin DH. RSR13, a potential athletic performance enhancement agent: detection in urine by gas chromatography/mass spectrometry. Rapid Commun Mass Spectrom 2001; 15(24): 2378–82CrossRef Breidbach A, Catlin DH. RSR13, a potential athletic performance enhancement agent: detection in urine by gas chromatography/mass spectrometry. Rapid Commun Mass Spectrom 2001; 15(24): 2378–82CrossRef
153.
go back to reference Richardson RS, Tagore K, Haseler LJ, et al. Increased VO2max with right-shifted Hb-O2 dissociation curve at a constant O2 delivery in dog muscle in situ. J Appl Physiol 1998; 84(3): 995–1002PubMed Richardson RS, Tagore K, Haseler LJ, et al. Increased VO2max with right-shifted Hb-O2 dissociation curve at a constant O2 delivery in dog muscle in situ. J Appl Physiol 1998; 84(3): 995–1002PubMed
154.
go back to reference Amberson WR, Flexner J, Steggerda FR, et al. On the use of Ringer-Locke solutions containing haemoglobin as a substitute for normal blood in mammals. J Cell Comp Physiol 1934; 5: 359–82CrossRef Amberson WR, Flexner J, Steggerda FR, et al. On the use of Ringer-Locke solutions containing haemoglobin as a substitute for normal blood in mammals. J Cell Comp Physiol 1934; 5: 359–82CrossRef
155.
go back to reference Amberson WR, Jennings JJ, Rhode CM. Clinical experience with haemoglobin-saline solutions. J Appl Physiol 1949; 1: 469–89PubMed Amberson WR, Jennings JJ, Rhode CM. Clinical experience with haemoglobin-saline solutions. J Appl Physiol 1949; 1: 469–89PubMed
156.
go back to reference Bunn HF. Subunit dissociation of certain abnormal human haemoglobins. J Clin Invest 1969; 48: 126–38PubMedCrossRef Bunn HF. Subunit dissociation of certain abnormal human haemoglobins. J Clin Invest 1969; 48: 126–38PubMedCrossRef
157.
go back to reference Mok W, Chen DE, Mazur A. Cross-linked haemoglobins as potential plasma protein extenders. Fed Proc 1975; 34: 1458–60PubMed Mok W, Chen DE, Mazur A. Cross-linked haemoglobins as potential plasma protein extenders. Fed Proc 1975; 34: 1458–60PubMed
158.
go back to reference Przybelski RJ, Daily EK, Kisicki JC, et al. Phase I study of the safety and pharmacologic effects of diaspirin cross-linked haemoglobin solution. Crit Care Med 1996; 24(12): 1993–2000PubMedCrossRef Przybelski RJ, Daily EK, Kisicki JC, et al. Phase I study of the safety and pharmacologic effects of diaspirin cross-linked haemoglobin solution. Crit Care Med 1996; 24(12): 1993–2000PubMedCrossRef
159.
go back to reference Sloan EP, Koenisberg M, Gens D, et al. Diaspirin cross-linked haemoglobin (DCLHb) in the treatment of severe traumatic hemorrhagic shock. JAMA 1999; 282: 1857–64PubMedCrossRef Sloan EP, Koenisberg M, Gens D, et al. Diaspirin cross-linked haemoglobin (DCLHb) in the treatment of severe traumatic hemorrhagic shock. JAMA 1999; 282: 1857–64PubMedCrossRef
161.
go back to reference Lee R, Atsumi N, Jacobs EE, et al. Ultrapure, stroma-free, polymerised bovine haemoglobin solution: evaluation of renal toxicity. J Surg Res 1989; 47: 407–11PubMedCrossRef Lee R, Atsumi N, Jacobs EE, et al. Ultrapure, stroma-free, polymerised bovine haemoglobin solution: evaluation of renal toxicity. J Surg Res 1989; 47: 407–11PubMedCrossRef
162.
go back to reference Hill SE. Oxygen therapeutics: current concepts. Can J Anaesth 2001; 48 (4 Suppl.): 32–40 Hill SE. Oxygen therapeutics: current concepts. Can J Anaesth 2001; 48 (4 Suppl.): 32–40
163.
go back to reference Sanders KE, Ackers G, Sligar S. Engineering and design of blood substitutes. Curr Opin Struct Biol 1996; 6: 534–40PubMedCrossRef Sanders KE, Ackers G, Sligar S. Engineering and design of blood substitutes. Curr Opin Struct Biol 1996; 6: 534–40PubMedCrossRef
164.
go back to reference Jia L, Bonaventura C, Bonaventura J, et al. S-ni-trosohaemoglobin: a dynamic activity of blood involved in vascular control. Nature 1996; 380: 221–6PubMedCrossRef Jia L, Bonaventura C, Bonaventura J, et al. S-ni-trosohaemoglobin: a dynamic activity of blood involved in vascular control. Nature 1996; 380: 221–6PubMedCrossRef
165.
go back to reference Privalle C, Talarico T, Keng T, et al. Pyridoxalated haemoglobin polyoxyethylene: a nitric oxide scavenger with antioxidant activity for the treatment of nitric oxide-induced shock. Free Radic Biol Med 2000; 28(10): 1507–17PubMedCrossRef Privalle C, Talarico T, Keng T, et al. Pyridoxalated haemoglobin polyoxyethylene: a nitric oxide scavenger with antioxidant activity for the treatment of nitric oxide-induced shock. Free Radic Biol Med 2000; 28(10): 1507–17PubMedCrossRef
166.
go back to reference D’Agnillo F, Chang TMS. Polyhemoglobin-superoxide dismutase-catalase as a blood substitute with antioxidant properties. Nat Biotech 1998; 16: 667–71CrossRef D’Agnillo F, Chang TMS. Polyhemoglobin-superoxide dismutase-catalase as a blood substitute with antioxidant properties. Nat Biotech 1998; 16: 667–71CrossRef
167.
go back to reference Kluger R, Wodzinska J, Jones RT, et al. Three-point cross-linking potential red cell substitutes from the reaction of trimesoyl tris (methylphosphate) with hemoglobin. Biochemistry 1992 Aug; 31: 7551–9PubMedCrossRef Kluger R, Wodzinska J, Jones RT, et al. Three-point cross-linking potential red cell substitutes from the reaction of trimesoyl tris (methylphosphate) with hemoglobin. Biochemistry 1992 Aug; 31: 7551–9PubMedCrossRef
168.
go back to reference Bucci E, Razynska A, Kwansa H, et al. Production and characteristics of an infusible oxygen-carrying fluid based on hemoglobin intramolecularly cross-linked with sebaci acid. J Lab Clin Med 1996 Aug; 128(2): 146–53PubMedCrossRef Bucci E, Razynska A, Kwansa H, et al. Production and characteristics of an infusible oxygen-carrying fluid based on hemoglobin intramolecularly cross-linked with sebaci acid. J Lab Clin Med 1996 Aug; 128(2): 146–53PubMedCrossRef
169.
go back to reference Buehler PW, Mehendale S, Wang H, et al. Resuscitative effects of polynitroxylated α-cross-linked haemoglobin following severe hemorrhage in the rat. Free Radic Biol Med 2000; 29(8): 764–74PubMedCrossRef Buehler PW, Mehendale S, Wang H, et al. Resuscitative effects of polynitroxylated α-cross-linked haemoglobin following severe hemorrhage in the rat. Free Radic Biol Med 2000; 29(8): 764–74PubMedCrossRef
170.
go back to reference Nakai K, Togashi H, Yasukohchi T, et al. Preparation and characterization of SNO-PEG-haemoglobin as a candidate for oxygen transporting material. Int J Artif Organs 2001; 24: 322–8PubMed Nakai K, Togashi H, Yasukohchi T, et al. Preparation and characterization of SNO-PEG-haemoglobin as a candidate for oxygen transporting material. Int J Artif Organs 2001; 24: 322–8PubMed
171.
go back to reference Marden MC, Kiger L, Poyart C, et al. Modulation of the oxygen affinity of cobalt-porphyrin by globin. FEBS Lett 2000; 472: 221–4PubMedCrossRef Marden MC, Kiger L, Poyart C, et al. Modulation of the oxygen affinity of cobalt-porphyrin by globin. FEBS Lett 2000; 472: 221–4PubMedCrossRef
172.
go back to reference Doherty DH, Doyle MP, Curry SR, et al. Rate of reaction with nitric oxide determines the hypertensive effect of cell-free hemoglobin. Nat Biotech 1998 Jul; 16(7): 672–6CrossRef Doherty DH, Doyle MP, Curry SR, et al. Rate of reaction with nitric oxide determines the hypertensive effect of cell-free hemoglobin. Nat Biotech 1998 Jul; 16(7): 672–6CrossRef
173.
go back to reference Kumar R, Manjula BN. Red cell substitutes: basic principles and clinical application. In: Rudolph AS, Rabinovici R, Feuerstein GZ, editors. New York: Marcel Dekker, 1997: 309–24 Kumar R, Manjula BN. Red cell substitutes: basic principles and clinical application. In: Rudolph AS, Rabinovici R, Feuerstein GZ, editors. New York: Marcel Dekker, 1997: 309–24
174.
go back to reference Dieryck W, Pagnier J, Poyart C, et al. Human haemoglobin from transgenic tobacco. Nature 1997 Mar; 386(6620): 29–30PubMedCrossRef Dieryck W, Pagnier J, Poyart C, et al. Human haemoglobin from transgenic tobacco. Nature 1997 Mar; 386(6620): 29–30PubMedCrossRef
175.
go back to reference Komiyama N, Tame J, Nagai K. A hemoglobin-based blood substitute: transplanting a novel allosteric effect of crocodile Hb. Biol Chem 1996 Sep; 377: 543–8PubMed Komiyama N, Tame J, Nagai K. A hemoglobin-based blood substitute: transplanting a novel allosteric effect of crocodile Hb. Biol Chem 1996 Sep; 377: 543–8PubMed
176.
go back to reference Chang TMS. Future prospects for artificial blood. Trends Tech 1999; 17: 61–7 Chang TMS. Future prospects for artificial blood. Trends Tech 1999; 17: 61–7
177.
go back to reference Djordevich L, Ivankovich AD. Progress in development of synthetic erythrocytes made by encapsulation of haemoglobin. Adv Exp Med Biol 1988; 238: 171–97CrossRef Djordevich L, Ivankovich AD. Progress in development of synthetic erythrocytes made by encapsulation of haemoglobin. Adv Exp Med Biol 1988; 238: 171–97CrossRef
178.
go back to reference Rabinovici R, Rudolph AS, Feuerstein G. Characterization of hemodynamic, hematologic, and biochemical responses to administration of liposome-encapsulated haemoglobin in the conscious, free moving rat. Circ Shock 1989; 29: 115–32PubMed Rabinovici R, Rudolph AS, Feuerstein G. Characterization of hemodynamic, hematologic, and biochemical responses to administration of liposome-encapsulated haemoglobin in the conscious, free moving rat. Circ Shock 1989; 29: 115–32PubMed
179.
go back to reference Sakai H, Tsai AG, Rohlfs RJ, et al. Microvascular responses to hemodilution with Hb vesicles as red blood cell substitutes: influence of O2 affinity. Am J Physiol 1999 Feb; 276 (2 Pt 2): 553–62H Sakai H, Tsai AG, Rohlfs RJ, et al. Microvascular responses to hemodilution with Hb vesicles as red blood cell substitutes: influence of O2 affinity. Am J Physiol 1999 Feb; 276 (2 Pt 2): 553–62H
180.
go back to reference Usuba A, Motoki R, Miyauchi Y, et al. Effect of neo red cells on the canine hemorrhagic shock model. Int J Artif Organs 1994; 14: 739–44 Usuba A, Motoki R, Miyauchi Y, et al. Effect of neo red cells on the canine hemorrhagic shock model. Int J Artif Organs 1994; 14: 739–44
181.
go back to reference Rabinovici R, Rudolph AS, Vernick J, et al. A new salutary resuscitative fluid: liposome encapsulated haemoglobin/hyper-tonic saline solution. J Trauma 1993; 35: 121–6PubMedCrossRef Rabinovici R, Rudolph AS, Vernick J, et al. A new salutary resuscitative fluid: liposome encapsulated haemoglobin/hyper-tonic saline solution. J Trauma 1993; 35: 121–6PubMedCrossRef
182.
go back to reference Farmer MC, Johnson SA, Beissinger RL, et al. Liposome-encapsulated haemoglobin: a synthetic red cell. Adv Exp Med Biol 1988; 238: 161–70PubMedCrossRef Farmer MC, Johnson SA, Beissinger RL, et al. Liposome-encapsulated haemoglobin: a synthetic red cell. Adv Exp Med Biol 1988; 238: 161–70PubMedCrossRef
183.
go back to reference Tsuchida E. Synthesis and characterization of artificial red cell (ARC). Biomater Artif Cells Immobilization Biotechnol 1992; 20(2–4): 337–44PubMed Tsuchida E. Synthesis and characterization of artificial red cell (ARC). Biomater Artif Cells Immobilization Biotechnol 1992; 20(2–4): 337–44PubMed
184.
go back to reference Dietz NM, Joyner MJ, Warner MA. Blood substitutes: fluids, drugs, or miracles solutions? Anesth Analg 1996; 82: 390–405PubMed Dietz NM, Joyner MJ, Warner MA. Blood substitutes: fluids, drugs, or miracles solutions? Anesth Analg 1996; 82: 390–405PubMed
185.
go back to reference Szebeni J, Fontana JL, Wassef NM, et al. Hemodynamic changes induced by liposomes and liposome-encapsulated haemoglobin in pigs: a model for pseudoallergic cardiopulmonary reactions to liposomes, role of complement and inhibition by soluble CR1 and anti-C5a antibody. Circulation 1999; 99: 2302–9PubMedCrossRef Szebeni J, Fontana JL, Wassef NM, et al. Hemodynamic changes induced by liposomes and liposome-encapsulated haemoglobin in pigs: a model for pseudoallergic cardiopulmonary reactions to liposomes, role of complement and inhibition by soluble CR1 and anti-C5a antibody. Circulation 1999; 99: 2302–9PubMedCrossRef
186.
go back to reference Chang TMS, Yu WP. Nanoencapsulation of haemoglobin and red blood cell enzymes based on nanotechnology and biodegradable polymer. In: Chang TMS, editor. Blood substitutes: principles, methods, products and clinical trials. Basel: Karger AG, 2000: 216–31 Chang TMS, Yu WP. Nanoencapsulation of haemoglobin and red blood cell enzymes based on nanotechnology and biodegradable polymer. In: Chang TMS, editor. Blood substitutes: principles, methods, products and clinical trials. Basel: Karger AG, 2000: 216–31
187.
go back to reference Haney CR, Buehler PW, Gutil A. Purification and chemical modifications of haemoglobin in developing based oxygen carriers. Adv Drug Deliv Rev 2000 Feb 28; 40(3): 153–69PubMedCrossRef Haney CR, Buehler PW, Gutil A. Purification and chemical modifications of haemoglobin in developing based oxygen carriers. Adv Drug Deliv Rev 2000 Feb 28; 40(3): 153–69PubMedCrossRef
188.
go back to reference Carmichael FJ. Recent developments in haemoglobin-based oxygen carriers: an update on clinicals trials. Transfus Apheresis Sci 2001 Feb; 24(1): 17–21CrossRef Carmichael FJ. Recent developments in haemoglobin-based oxygen carriers: an update on clinicals trials. Transfus Apheresis Sci 2001 Feb; 24(1): 17–21CrossRef
189.
go back to reference Hughes Jr GS, Yancey EY, Albrecht R, et al. Haemoglobin-based oxygen carrier preserves submaximal exercise capacity in humans. Clin Pharmacol Ther 1995; 58(4): 434–43PubMedCrossRef Hughes Jr GS, Yancey EY, Albrecht R, et al. Haemoglobin-based oxygen carrier preserves submaximal exercise capacity in humans. Clin Pharmacol Ther 1995; 58(4): 434–43PubMedCrossRef
190.
go back to reference Riess JG. Fluorocarbon-based in vivo oxygen transport and delivery systems. Vox Sang 1991; 61: 225–39PubMedCrossRef Riess JG. Fluorocarbon-based in vivo oxygen transport and delivery systems. Vox Sang 1991; 61: 225–39PubMedCrossRef
191.
go back to reference Grote G, Steur K, Muller R, et al. O2 and CO2 solubility of the fluorocarbon emulsion Fluosol-DA 20% and O2 and CO2 dissociates curves of blood Fluosol-DA 20% mixtures. Adv Exp Med Biol 1985; 191: 453–61PubMedCrossRef Grote G, Steur K, Muller R, et al. O2 and CO2 solubility of the fluorocarbon emulsion Fluosol-DA 20% and O2 and CO2 dissociates curves of blood Fluosol-DA 20% mixtures. Adv Exp Med Biol 1985; 191: 453–61PubMedCrossRef
192.
go back to reference Habler O, Kleen M, Messmer K. Clinical potential of intravenously administered perfluorocarbons. Acta Anaesthesiol Scand Suppl 1997; 111: 256–8PubMed Habler O, Kleen M, Messmer K. Clinical potential of intravenously administered perfluorocarbons. Acta Anaesthesiol Scand Suppl 1997; 111: 256–8PubMed
193.
go back to reference Sakas DE, Whittaker KW, Crowell RM, et al. Perfluorocarbons: recent developments and implications for neurosurgery. J Neurosurg 1996; 85: 248–54PubMedCrossRef Sakas DE, Whittaker KW, Crowell RM, et al. Perfluorocarbons: recent developments and implications for neurosurgery. J Neurosurg 1996; 85: 248–54PubMedCrossRef
194.
go back to reference Kaufman RJ. Clinical development of perfluorocarbon-based emulsions are red cell substitutes. In: Winslow RM, Vandergriff KD, Intaglietta M, editors. Blood substitutes: physiological basis of efficacy. Boston (MA): Birkhauser, 1995: 53–75CrossRef Kaufman RJ. Clinical development of perfluorocarbon-based emulsions are red cell substitutes. In: Winslow RM, Vandergriff KD, Intaglietta M, editors. Blood substitutes: physiological basis of efficacy. Boston (MA): Birkhauser, 1995: 53–75CrossRef
195.
go back to reference Goodnough LT, Scott MG, Monk TG. Oxygen carriers as blood substitutes. Clin Orthop 1998; 357: 89–100PubMedCrossRef Goodnough LT, Scott MG, Monk TG. Oxygen carriers as blood substitutes. Clin Orthop 1998; 357: 89–100PubMedCrossRef
196.
go back to reference Faithfull NS. Mechanisms and efficacy of fluorochemical oxygen transport and delivery. Artif Cells Blood Substit Immobil Biotechnol 1994; 22(2): 181–97PubMedCrossRef Faithfull NS. Mechanisms and efficacy of fluorochemical oxygen transport and delivery. Artif Cells Blood Substit Immobil Biotechnol 1994; 22(2): 181–97PubMedCrossRef
197.
go back to reference Mitten RM, Burgan AR, Hamblin A, et al. Dose related biodistribution and elimination of 100% PFOB emulsion. Biomater Artif Cells Artif Organs 1988; 16(1–3): 683–4 Mitten RM, Burgan AR, Hamblin A, et al. Dose related biodistribution and elimination of 100% PFOB emulsion. Biomater Artif Cells Artif Organs 1988; 16(1–3): 683–4
198.
go back to reference Audran M, Krafft MP, De Ceaurriz J, et al. Assay method for the perfluorooctyl bromide (perflubron) in rat blood by gas chromatography-mass spectrometry. J Chromatogr B Biomed Sci Appl 1999 Aug; 734(2): 267–76PubMedCrossRef Audran M, Krafft MP, De Ceaurriz J, et al. Assay method for the perfluorooctyl bromide (perflubron) in rat blood by gas chromatography-mass spectrometry. J Chromatogr B Biomed Sci Appl 1999 Aug; 734(2): 267–76PubMedCrossRef
199.
go back to reference Audran M, Krafft MP, De Ceaurriz J, et al. Determination of perfluorodecalin and perfluoro-N-methylcyclohexylpiperidine in rat blood by gas chromatography-mass spectrometry. J Chromatogr B Biomed Sci Appl 2000; 745: 333–43PubMedCrossRef Audran M, Krafft MP, De Ceaurriz J, et al. Determination of perfluorodecalin and perfluoro-N-methylcyclohexylpiperidine in rat blood by gas chromatography-mass spectrometry. J Chromatogr B Biomed Sci Appl 2000; 745: 333–43PubMedCrossRef
200.
go back to reference Rivier L. The doping products of tomorrow. Ann Toxicol Analytique 2000; 12(1): 79–89CrossRef Rivier L. The doping products of tomorrow. Ann Toxicol Analytique 2000; 12(1): 79–89CrossRef
201.
go back to reference Mathurin JC, De Ceaurriz J, Audran M, et al. Detection of perfluorocarbons in blood by headspace solid-phase microextraction combined with gas chromatography/mass spectrometry. Biomed Chromatogr 2001; 15(7): 443–51PubMedCrossRef Mathurin JC, De Ceaurriz J, Audran M, et al. Detection of perfluorocarbons in blood by headspace solid-phase microextraction combined with gas chromatography/mass spectrometry. Biomed Chromatogr 2001; 15(7): 443–51PubMedCrossRef
202.
go back to reference Schumacher YO, Schmid A, Dinkelmann S, et al. Artificial oxygen carriers: the new doping threat in endurance sport? Int J Sports Med 2001; 22: 566–71PubMedCrossRef Schumacher YO, Schmid A, Dinkelmann S, et al. Artificial oxygen carriers: the new doping threat in endurance sport? Int J Sports Med 2001; 22: 566–71PubMedCrossRef
Metadata
Title
Drugs for Increasing Oxygen Transport and Their Potential Use in Doping
A Review
Authors
Aurelie Gaudard
Emmanuelle Varlet-Marie
Francoise Bressolle
Michel Audran
Publication date
01-03-2003
Publisher
Springer International Publishing
Published in
Sports Medicine / Issue 3/2003
Print ISSN: 0112-1642
Electronic ISSN: 1179-2035
DOI
https://doi.org/10.2165/00007256-200333030-00003

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