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Specific hemoperfusion through agarose acrobeads

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Abstract

Agarose acrobeads were produced by encapsulating polyacrolein microspheres (acrobeads) of 0.2 μm average diameter within an agarose matrix. Crosslinked agarose acrobeads of diameters ranging from 0.5 to 0.8 mm were found to be optimal spheres for specific hemoperfusion purposes. Agarose provides the biocompatibility and mechanical strength of the agarose acrobeads. Acrobeads contain a high aldehyde-group content through which various amino ligands, i.e., proteins, antigens, antibodies, enzymes, and so on, can be covalently bound in a single step under physiological pH (or other pH). Thus, antibodies, antigens, or toxic materials may be directly removed from whole blood by hemoperfusion. During in vitro and in vivo hemoperfusion trials, the content of erythrocytes, leukocytes, and thrombocytes was essentially unaltered. Likewise, a battery of the soluble blood components (Cl-, K+, Na+, Ca2+, PO -4 ), total proteins, albumin, and C 4 component of the complement cascade, as well as the enzymes SGOT, LDH, and alkaline phosphatase, remained constant within narrow limits during the hemoperfusion procedure. The chemical and physical structure of the beads is stable; neither acrolein nor bead fragments were detected in hemoperfusion trials. Similarly, leakage of antibody bound to the agarose acrobeads into the blood is insignificant.

Thus far, we have demonstrated the efficacy of the crosslinked agarose acrobeads for extracorporeal removal of “unwanted” substances from whole blood in the following systems: (a) removal of specific antigens (digoxin or paraquat removal with antidigoxin or antiparaquat antibodies bound to the acrobeads, respectively), (b) removal of specific antibody (antiBSA) removal with BSA bound to the beads), (c) removal of immune complexes (BSA-antiBSA complex removal with C1q bound to acrobeads), and (d) removal of specific metals (removal of iron with deferoxamine bound to the agarose acrobeads).

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References

  1. Yatzidis, H. (1964),Proc. Eur. Dial. Transpl. Assoc. 1, 83.

    Google Scholar 

  2. Pallota, A. J., and Koppanyi, T. (1960),J. Pharm. Exp. Therap. 128, 318.

    Google Scholar 

  3. Rosenbaum, J. L., Kramer, M. S., Raja, R., and Boreyko, C. (1971),N. Eng. J. Med. 284, 583.

    Article  Google Scholar 

  4. Chang, T. M. S., and Malave, N. (1970),Trans. Am. Soc. Art. Int. Org. 16, 141.

    CAS  Google Scholar 

  5. Terman, D. S., Tavel, T., Petty, D., Tavel, A., Harbeck, R., and Carr, R. (1976),J. Immunol. 116, 1337.

    CAS  Google Scholar 

  6. Andrade, J. D., Kunitomo, K., Van Wagenen, R., Kastigir, D., Gough, D., and Kolff, W. J. (1971),Trans. Am. Soc. Art. Int. Org. 17, 222.

    CAS  Google Scholar 

  7. Holloway, C. J. K., Harstick, K., and Brunner, C. (1979),Int. J. Art. Org. 2, 81.

    CAS  Google Scholar 

  8. Chang, T. M. S. (1975),Kidney Int. 7, S 387.

    Google Scholar 

  9. Chang, T. M. S., Gonda, A., Dirks, J. H., and Malave, N. (1971),Trans. Am. Soc. Art. Int. Org. 17, 246.

    CAS  Google Scholar 

  10. Gelfand, M. C., and Winchester, J. F. (1980),Clin. Toxicol. 17, 583.

    CAS  Google Scholar 

  11. Gibson, T. P. (1980),Clin. Toxicol. 17, 501.

    CAS  Google Scholar 

  12. Kostyniak, P. J., Clarkson, T. W., and Abbasi, A. H. (1977),J. Pharm. Exp. Ther. 203, 253.

    CAS  Google Scholar 

  13. Winchester, J. F., Gelfand, M. C., and Tilstone, W. J. (1978),Drug Metab. Rev. 5, 69.

    Article  Google Scholar 

  14. Sketris, I. S., and Skoutakis, V. A. (1981),Clin. Toxicol. Consul. 3, 100.

    CAS  Google Scholar 

  15. Rosenbaum, J. L., Kramer, M. S., Raja, R. M., King, M. J., and Bolisay, C. G. (1980),Clin. Toxicol. 17, 493.

    CAS  Google Scholar 

  16. Chang, T. M. S. (1977),Biomedical Applications of Immobilized Enzymes and Proteins, vols. 1 and 2. Plenum, New York.

    Google Scholar 

  17. Seideman, S., Lotan, N., Tabak, A., Manor, D., Mor, L., Taitelman, U., Brook, J., and Tzipinik, A. (1984),Appl. Biochem. Biotechnol. 10, 167.

    Article  Google Scholar 

  18. Winchester, J. F., Gelfand, M. C., Knepshield, J. H., and Schreiner, G. E. (1977),Trans. Am. Soc. Art. Int. Org. 23, 762.

    CAS  Google Scholar 

  19. Schenkein, I., Bystryn, J.-C., and Uhr, J. W. (1971),J. Clin. Invest. 50, 1864.

    CAS  Google Scholar 

  20. Lyle, L. R., Parker, B. M., and Parker, C. W. (1974),J. Immunol. 113, 517.

    CAS  Google Scholar 

  21. Terman, D. S., Tavel, T., Petty, D., Racic, M. R., and Buffaloe, G. (1977),Clin. Exp. Immunol. 28, 180.

    CAS  Google Scholar 

  22. Terman, D. S., Young, J. B., Shearer, W. T., Ayus, C., Lehane, D., Matioli, C., Espada, R., Howell, J. F., Yamamoto, T., Zaleski, H. I., Miller, L., Frommer, P., Feldman, L., Henry, J. F., Tillquist, R., Cook, G., and Daskal, Y. (1981),N. Eng. J. Med. 305, 1195.

    Article  CAS  Google Scholar 

  23. Besa, E. C., Ray, P. K., Swami, V. K., Idiculla, A., Rhoads, J. E., Bassett, J. G., Joseph, R. R., and Cooper, D. R. (1981),Am. J. Med. 71, 1035.

    Article  CAS  Google Scholar 

  24. Scharschmidt, B. F., Martin, J. F., and Shapiro, L. J. (1977),J. Lab. Clin. Med. 89, 110.

    CAS  Google Scholar 

  25. Margel, S., Beitler, U., and Offarim, M. (1982),J. Cell Sci. 56, 157.

    CAS  Google Scholar 

  26. Margel, S., and Offarim, M. (1983),Anal. Biochem. 128, 342.

    Article  CAS  Google Scholar 

  27. Marcus, L., Offarim, M., and Margel, S. (1982),Biomat., Med. Dev., Art. Org. 10, 157.

    CAS  Google Scholar 

  28. Margel, S., and Hirsch, J. (1981),Biomat., Med. Dev., Art. Org. 9, 107.

    CAS  Google Scholar 

  29. Margel, S. (1981),J. Med. Chem. 24, 1263.

    Article  CAS  Google Scholar 

  30. Rembaum, A., and Margel, S. (1978),Bri. Polymer. J. 10, 275.

    Article  CAS  Google Scholar 

  31. Margel, S., Offarim, M., and Eshhar, Z. (1983),J. Cell Sci. 62, 149.

    CAS  Google Scholar 

  32. Margel, S., Zisblatt, S., and Rembaum, A. (1971),J. Immunol. Methods 28, 341.

    Article  Google Scholar 

  33. Lazar, A., and Margel, S. (1985),Dev. Biol. Standardiz. 60, 457.

    CAS  Google Scholar 

  34. Pines, M., and Margel, S. (1985),J. Immunoassay, in press.

  35. Margel, S. (1982),FEBS Lett. 145, 341.

    Article  CAS  Google Scholar 

  36. Porath, J., Loas, T., and Jansen, J. (1975),J. Chromatog. 103, 49.

    Article  CAS  Google Scholar 

  37. Marcus, L., Mashiah, A., Offarim, M., and Margel, S. (1984),J. Biomed. Mat. Res. 18, 1153.

    Article  CAS  Google Scholar 

  38. Margel, S., Marcus, L., Savin, H., Offarim, M., and Mashiah, A. (1984),Biomat., Med. Dev., Art. Org. 12, 25.

    CAS  Google Scholar 

  39. Marcus, L., Margel, S., Savin, H., Offarim, M., and Ravid, M. (1985),Am. Heart J. (in press).

  40. Gazitt, Y., Margel, S., Lerner, A., Wands, J. R., and Shouval, D. (1985),Immun. Lett. 11, 1.

    Article  CAS  Google Scholar 

  41. Azhari, R., Labes, A., Haviv, Y., and Margel, S. (1984), submitted for publication.

  42. Horowitz, D., Margel, S., and Shimoni, T. (1984),Biomaterials 6, 9.

    Article  Google Scholar 

  43. Mashiah, A., Marcus, L., Savin, H., and Margel S. (1984),Lab. Anim. 18, 26.

    Article  CAS  Google Scholar 

  44. Kohn, J., and Wilchek, M. (1984),Appl. Biochem. Biotechnol. 9, 285.

    CAS  Google Scholar 

  45. Papandopoulou, Z. L., and Novello, A. C. (1982),Fed. Clin. N. Am. 29, 1039.

    Google Scholar 

  46. Smith, T. W., and Haber, E. (1973),N. Eng. J. Med. 289, 1125.

    Article  CAS  Google Scholar 

  47. Carvallo, A., Ramirez, B., Honig, H., Knepshield, J., Schreiner, G. E., and Gelfand, M. D. (1975),Trans. Am. Soc. Art. Int. Org. 22, 718.

    Google Scholar 

  48. Tobin, M., Steinbach, J., and Mookerjee, B. (1977),Trans. Am. Soc. Art. Org. 23, 730.

    CAS  Google Scholar 

  49. Gibson, T. P. Lucas, S. V., Nelson, H. A., Atkinson, Jr., A. J., Okita, G. T., and Ivanovich, P. (1978),J. Lab. Clin. Med. 240, 673.

    Google Scholar 

  50. Smiley, J. W., March, N. M., and Del Guerco, T. (1978),J. Am. Med. Assoc. 240, 2736.

    Article  CAS  Google Scholar 

  51. Ackerman, G. L., Doherty, J. E., and Flanagan, W. J. (1967),Ann. Int. Med. 67, 718.

    CAS  Google Scholar 

  52. Iisalo, E., and Forsstrom, J. (1974),Ann. Clin. Res. 6, 203.

    CAS  Google Scholar 

  53. Schmidt, D. H., and Butler, Jr, V. P. (1971),J. Clin. Invest. 50, 1738.

    CAS  Google Scholar 

  54. Curd, J., Smith, T. W., Jaton, J.-C., and Haber, E. (1971),Proc. Natl. Acad. Sci. USA 68, 2401.

    Article  CAS  Google Scholar 

  55. Smith, T. W., Haber, E., Yeatman, L., and Butler, Jr, V. P. (1976),N. Eng. J. Med. 294, 797.

    Article  CAS  Google Scholar 

  56. Smith, T. W., Butler, Jr, V. P., Haber, E., Fozzard, H., Marcus, F. I., Bremner, W. F., Schulman, I., and Phillips, A. (1982),N. Eng. J. Med. 307, 1357.

    Article  CAS  Google Scholar 

  57. Editorial, Paraquat Poisoning (1971),Lancet 2, 1018.

    Google Scholar 

  58. Tabei, K., Asano, Y., and Hosoda, S. (1982),Art. Org. 6, 37.

    CAS  Google Scholar 

  59. Cavelli, R. D., and Fletcher, K. (1977), inBiochemical Mechanism of Paraquat Poisoning, Autor, A. P., ed., Academic, London.

    Google Scholar 

  60. Eliahou, H. E., Almog, C., Gura, V., and Iaina, A. (1973),Israel J. Med. Sci. 9, 459.

    CAS  Google Scholar 

  61. Fisher, H. K., Humphries, M., and Balis, R. (1971),Ann. Int. Med. 75, 731.

    CAS  Google Scholar 

  62. Mascie-Taylor, B. H., Thompson, J., and Daviso, A. M. (1983),Lancet 8338, 1376.

    Article  Google Scholar 

  63. Solfrank, G., Mathes, G. V., Clarman, M., and Beyer, K. H. (1977),Acta Pharmacol. Toxicol. (suppl.) 41, 91.

    Google Scholar 

  64. Okonek, S., Hofmann, A., and Henningson, B. (1976),Arch. Toxicol. 36, 43.

    Article  CAS  Google Scholar 

  65. Winchester, J. F., and Gelfand, M. C. (1978),Drug Metab. Rev. 8, 69.

    Article  CAS  Google Scholar 

  66. Azhari, R. (1984), Thesis for Master of Science, Weizmann Inst. of Science, Rehovot, Israel.

    Google Scholar 

  67. Roitt, I. (1980),Essential Immunology, Blackwell Scientific, Oxford.

    Google Scholar 

  68. Shumak, K. H., and Rock, G. A. (1984),N. Eng. J. Med. 310, 762.

    Article  CAS  Google Scholar 

  69. Morimoto, C., Sano, H., Abe, T., Homma, M., and Steinberg, A. D. (1982),J. Immunol. 129, 1960.

    CAS  Google Scholar 

  70. Barkas, T., Boyle, R. S., and Behan, P. O. (1981),J. Clin. Lab. Immunol. 5, 27.

    CAS  Google Scholar 

  71. Kunkel, H. G. (1961),J. Clin. Invest. 40, 117.

    Article  CAS  Google Scholar 

  72. Wands, J. R., and Zuraski, V. R. (1981),Gastroenterology. 80, 225.

    CAS  Google Scholar 

  73. Brown, S., Howard, C. R., Steward, M. W., Ajdukiewicz, A. B., and Whittle, H. C. (1984),Clin. Exp. Immunol. 55, 335.

    Google Scholar 

  74. Gazitt, Y., Klein, G., and Sulitzeanu, D. (1982),Int. J. Cancer 29, 645.

    Article  CAS  Google Scholar 

  75. Theophilopoulous, A. N., and Dixon, F. J. (1980),Adv. Immunol. 28, 89.

    Google Scholar 

  76. Wallmark, A., Grubb, A. Freiburghaus, C., Flodgren, P., Husberg, B., Lindholm, T., Lindstrom, C., Thysell, H., and Sjogren, H. O. (1984),Art. Org. 8, 72.

    CAS  Google Scholar 

  77. Theophilopoulous, A. N., Eisemberg, R., and Dixon, F. J. (1978),J. Clin. Invest. 61, 1570.

    Google Scholar 

  78. Gilead, Z., Gazitt, Y., Klein, D., and Sulitzenau, D. (1980),Methods Enzymol. 74, 664.

    Article  Google Scholar 

  79. Gazitt, Y., Gilead, Z., Klein, G., and Sulitzeanu, D. (1981),J. Immunol. Methods 43, 49.

    Article  CAS  Google Scholar 

  80. Casali, P., and Lambert, P. H. (1979),Clin. Exp. Immunol. 37, 295.

    CAS  Google Scholar 

  81. O’Brien, R. T. (1977),Semin. Hematol. 14, 115.

    CAS  Google Scholar 

  82. Buja, L. M., and Roberts, W. C. (1971),Am. J. Med. 51, 209.

    Article  CAS  Google Scholar 

  83. Schafer, A. I., Cheron, R. G., Dluhy, R., Cooper, B., Gleason, R. E., Soeldner, J. S., and Bunn, H. F. (1981),N. Eng. J. Med. 304, 319.

    Article  CAS  Google Scholar 

  84. McCance, R. A., and Widdowson, E. M. (1937),Lancet 2, 680.

    Article  Google Scholar 

  85. Propper, R., and Nathan, D. (1982),Ann. Rev. Med. 33, 509.

    Article  CAS  Google Scholar 

  86. Finch, S. C., and Finch, C. A. (1955),Medicine 34, 381.

    CAS  Google Scholar 

  87. Stein, M., Blayney, D., and Feit, T. (1976),West. J. Med. 125, 289.

    CAS  Google Scholar 

  88. Schafer, A. I. (1982), inHarrison’s Principles of Internal Medicine, (Update III), McGraw-Hill, NY, pp. 157–166.

    Google Scholar 

  89. Jacobs, A. (1977),Sem. Hematol. 14, 89.

    CAS  Google Scholar 

  90. Hershko, C. (1977),Prog. Hematol. 10, 105.

    CAS  Google Scholar 

  91. Bomford, A., and Williams, R. (1976),Q. J. Med. 45, 611.

    CAS  Google Scholar 

  92. Barry, M. Flynn, D. M., Letsky, E. A., and Risdon, R. A. (1974),Br. Med. J. 2, 16.

    CAS  Google Scholar 

  93. Modell, B. (1979),Prog. Hematol. 11, 267.

    CAS  Google Scholar 

  94. Keberle, H. (1964),Ann. N. Y. Acad. Sci. USA 119, 758.

    Article  CAS  Google Scholar 

  95. Davies, S. C., Hungerford, J. L., Arden, G. B., Marcus, R. E., Miller, M. H., and Huehns, E. R. (1977),Lancet 1, 977.

    Google Scholar 

  96. Rembold, C. M., Krumlovsky, F. A., Roxe, D. M., Fitzimmons, E., and Del Greco, F. (1982),Trans. Am. Soc. Art. Int. Org. 28, 621.

    CAS  Google Scholar 

  97. Chang, T. M. S., and Barre, P. (1983),Lancet 2, 1051.

    Article  CAS  Google Scholar 

  98. Ramirez, R. S., and Andrade, J. D. (1973),J. Macromolec. Sci.-Chem. A17, 1035.

    Google Scholar 

  99. Ramirez, R. S., and Andrade, J. D. (1976),J. Macromolec, Sci.-Chem. A10, 309.

    CAS  Google Scholar 

  100. Horowitz, D. (1984), Thesis for Master of Science, Weizmann Institute of Science, Rehovot, Israel.

    Google Scholar 

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Margel, S., Marcus, L. Specific hemoperfusion through agarose acrobeads. Appl Biochem Biotechnol 12, 37–66 (1986). https://doi.org/10.1007/BF02798578

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