Blood transfusion recipients are at risk of virus transmission, with hepatitis virus remaining the most frequent; however, the spread of AIDS into the general donor population raises fears concerning future HIV risk and risk from unidentified viruses. Our objective is to develop methods of virus sterilization, applicable to red cell (RBCC) and platelet concentrates (PC), which will eliminate this risk. Research will emphasize photosensitizers, especially aluminum phthalocyanine (AIPc) derivatives for the treatment of RBCC and PC, and psoralens for the treatment of PC. Current favorable results with sulfonated AIPc will be compared with positively charged and amphoteric phthalocyanines. Each has shown superior reactivity in other biological systems. Current results with AMT (a positively charged psoralen) will be extended. Attention will focus on the use of quenchers of hydroxyl radicals and other """"""""type l"""""""" reactants, which were recently shown to be advantageous in eliminating undesired side reactions observed with both photodynamic dyes and psoralens - without reducing the rate or extent of virus kill. Quenchers which scavenge both type l radicals and singlet oxygen will also be tested. Virus killing will be measured with vesicular stomatitis virus (and other marker viruses), HIV, and hepatitis C virus. Measurements of nucleic acid modification will also be made. Red cell and platelet integrity will be monitored immediately following treatment and on storage under standard blood bank conditions. Measurements will include hemoglobin release, K+ leakage, IgG binding, metabolic indicators such as glucose utilization, intracellular ATP and 2,3-DPG for RBC, and changes in platelet number, morphology, pH, aggregation response, and appearance/disappearance of selected membrane antigens, and the ability to correct an aspirin-induced thrombocytopathy in baboons. For both RBCC and PC, circulatory recovery and half-life, will be evaluated following autologous transfusion in rabbits and baboons. Neoimmunogenicity will be assessed in these baboon studies and also in a rabbit model using human RBCC and PC. Available information regarding the toxicology of compounds giving favorable results will be reviewed, and Ames testing performed.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL041221-05A2
Application #
2219937
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1988-07-01
Project End
1996-11-30
Budget Start
1993-12-01
Budget End
1994-11-30
Support Year
5
Fiscal Year
1994
Total Cost
Indirect Cost
Name
New York Blood Center
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10065
Zmudzka, B Z; Strickland, A G; Beer, J Z et al. (1997) Photosensitized decontamination of blood with the silicon phthalocyanine Pc 4: no activation of the human immunodeficiency virus promoter. Photochem Photobiol 65:461-4
Margolis-Nunno, H; Bardossy, L; Robinson, R et al. (1997) Psoralen-mediated photodecontamination of platelet concentrates: inactivation of cell-free and cell-associated forms of human immunodeficiency virus and assessment of platelet function in vivo. Transfusion 37:889-95
Ben-Hur, E; Oetjen, J; Horowitz, B (1997) Silicon phthalocyanine Pc 4 and red light causes apoptosis in HIV-infected cells. Photochem Photobiol 65:456-60
Zhao, X J; Lustigman, S; Li, Y S et al. (1997) Structure-activity and mechanism studies on silicon phthalocyanines with Plasmodium falciparum in the dark and under red light. Photochem Photobiol 66:282-7
Smetana, Z; Malik, Z; Orenstein, A et al. (1997) Treatment of viral infections with 5-aminolevulinic acid and light. Lasers Surg Med 21:351-8
Ben-Hur, E; Barshtein, G; Chen, S et al. (1997) Photodynamic treatment of red blood cell concentrates for virus inactivation enhances red blood cell aggregation: protection with antioxidants. Photochem Photobiol 66:509-12
Lustigman, S; Ben-Hur, E (1996) Photosensitized inactivation of Plasmodium falciparum in human red cells by phthalocyanines. Transfusion 36:543-6
Ben-Hur, E; Moor, A C; Margolis-Nunno, H et al. (1996) The photodecontamination of cellular blood components: mechanisms and use of photosensitization in transfusion medicine. Transfus Med Rev 10:15-22
Ben-Hur, E; Horowitz, B (1996) Virus inactivation in blood. AIDS 10:1183-90
Gottlieb, P; Margolis-Nunno, H; Robinson, R et al. (1996) Inactivation of Trypanosoma cruzi trypomastigote forms in blood components with a Psoralen and Ultraviolet A light. Photochem Photobiol 63:562-5

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