Background and Objectives The risk of transfusion‐transmitted bacterial infections as a result of the presence of bacteria in blood is one of the major concerns in transfusion medicine. The purpose of this study was to investigate whether bacteria inoculated into red blood cell concentrates can be inactivated by the INACTINE PEN110 pathogen‐reduction process. Four bacterial species were chosen for the study: anaerobic Gram‐positive Clostridium perfringens and Propionibacterium acnes, known to be transfusion‐transmitted; and two Gram‐negative species, Acinetobacter johnsonii and Acinetobacter lwoffii, recently reported to be a common cause of transfusion‐associated infections in Europe.Materials and Methods Identical units of leucoreduced red cell concentrates were inoculated with A. johnsonii, A. lwoffii, C. perfringens, or P. acnes. The 4 °C control units were put on storage immediately after receiving the spike. The test units were subjected to PEN110 treatment and then stored. The bacterial titre in all units was monitored during a 6‐week storage period.Results The PEN110 inactivation of all tested bacterial strains was time‐ and titre‐dependent. For A. johnsonii and A. lwoffii, no viable bacteria were detected in the units spiked with up to 104 colony‐forming units (CFU)/ml and treated with PEN110. For red cell units spiked with 104−105 CFU/ml of C. perfringens and P. acnes, no viable bacteria were detected in the units treated with PEN110. In control units, there was a gradual decrease in A. johnsonii, A. lwoffii and C. perfringens titres during cold storage, while P. acnes titres remained stable.Conclusions The PEN110 pathogen‐reduction process was demonstrated to inactivate high titres of A. johnsonii, A. lwoffii, C. perfringens and P. acnes in red cell concentrates.

2004-07-01·Vox sanguinis4区 · 医学

Induction of latent human cytomegalovirus by conventional gamma irradiation and prevention by treatment with INACTINE PEN110

4区 · 医学

Article

作者: V. Jayarama ; J. Marcello ; A. Ohagen ; V. Gibaja ; D. Lunderville ; A. Lazo ; J. Chapman ; J. Horrigan

Background and Objectives Two different leucocyte‐inactivation technologies – gamma irradiation and INACTINE PEN110 – were evaluated for their effects on cell‐associated human cytomegalovirus (CMV).Materials and Methods In vitro CMV‐infected cells were spiked into leucoreduced red blood cell concentrates (RCC) or medium at a final concentration of 0·5–1 × 107 cells/ml to mimic non‐leucoreduced levels of leucocytes. The spiked RCC/medium was divided into three equal units and treated with gamma irradiation at the US Food and Drug Administration (FDA)‐approved dose of 25 Gy, with 0·1% v/v PEN110 at 22 °C for 24 h, or stored at 4 °C as a control. The treated and control cells were recovered and tested using infectivity, viability and polymerase chain reaction (PCR) assays.Results Gamma‐irradiated CMV‐infected cells produced active virus, as shown by both infectivity assays and PCR quantification of viral DNA. PCR analysis demonstrated higher CMV DNA levels in gamma‐irradiated, latently infected monocytic THP‐1 cells than untreated control cells. The increased virus production in gamma‐irradiated cells was paralleled by an increased metabolic rate and the development of enlarged multinuclear cells. In contrast, PEN110 treatment terminated virus replication and completely inactivated the infected cell.Conclusions These results demonstrate that gamma irradiation, at levels currently used to treat RCC, has the capacity to induce expression of CMV, whereas PEN110 inhibits CMV replication and efficiently inactivates the infected cells.

2004-02-01·Transfusion3区 · 医学

Inhibition of xenogeneic GVHD by PEN110 treatment of donor human PBMNCs

3区 · 医学

Article

作者: di Leon, Gilbert ; Kim, Michael ; Freedman, John ; Chapman, John ; Purmal, Andrei ; Fast, Loren D. ; Semple, John W.

BACKGROUND: Development and characterization of methods for preventing transfusion‐associated GVHD have utilized in vitro studies with human WBCs and in vivo studies in animal models. The limitation of these assays is that the in vivo GVHD response of treated human WBCs has not been tested directly.STUDY DESIGN AND METHODS: PBMNCs isolated from nonleukoreduced RBC units exposed to gamma irradiation, treated with PEN110 or PBS, were tested for their ability to induce xenogeneic GVHD when injected into severe combined immunodeficient (SCID) mice.RESULTS: These studies showed that the SCID mice injected with PBS‐treated PBMNCs developed serum levels of human immunoglobulin that were followed by weight loss and display of ruffled fur characteristic of xenogeneic GVHD in these mice. In contrast, SCID mice injected with PEN110‐treated or gamma‐irradiated PBMNCs did not exhibit any of these responses.CONCLUSIONS: In these studies PEN110 treatment and gamma irradiation were equally effective at preventing in vivo GVHD responses when the treated cells were injected into SCID recipients. These results are consistent with previous results obtained when these two treatment methods were compared with in vitro studies with PBMNCs and in vivo studies in mouse models.

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