Treatment of Platelet Products with Riboflavin and UV Light: Effectiveness Against High Titer Bacterial Contamination.

Contamination of platelet units by bacteria has long been acknowledged as a significant transfusion risk due to their post-donation storage conditions. Products are routinely stored at 22 °C on an agitating shaker, a condition that can promote bacterial growth. Although the total number of bacteria believed to be introduced into a platelet product is extremely low, these bacteria can multiply to a very high titer prior to transfusion, potentially resulting in serious adverse events. The aim of this study was to evaluate a riboflavin based pathogen reduction process against a panel of bacteria that have been identified as common contaminants of platelet products. This panel included the following organisms: S. epidermidis, S. aureus, S. mitis, S. pyogenes, S. marcescens, Y. enterocolitica, B. neotomae, B. cereus, E. coli, P. aeruginosa and K. pneumoniae. Each platelet unit was inoculated with a high bacterial load and samples were removed both before and after treatment. A colony forming assay, using an end point dilution scheme, was used to determine the pre-treatment and post-treatment bacterial titers. Log reduction was calculated by subtracting the post-treatment titer from the pre-treatment titer. The following log reductions were observed: S. epidermidis 4.7 log (99.998%), S. aureus 4.8 log (99.998%), S. mitis 3.7 log (99.98%), S. pyogenes 2.6 log (99.7%), S. marcescens 4.0 log (99.99%), Y. enterocolitica 3.3 log (99.95%), B. neotomae 5.4 log (99.9996%), B. cereus 2.6 log (99.7%), E. coli ≥5.4 log (99.9996%), P. aeruginosa 4.7 log (99.998%) and K. pneumoniae 2.8 log (99.8%). The results from this study suggest the process could help to lower the risk of severe adverse transfusion events associated with bacterial contamination.

Inactivation of viruses in platelet and plasma products using a riboflavin-and-UV-based photochemical treatment.

BACKGROUND: Multilayered blood safety programs reduce the risk of transfusion-transmitted diseases; however, there remains a risk of window period transmission of screened viruses and transmission of unscreened and emerging viruses from asymptomatic donors. To reduce this risk, a riboflavin-and-UV-light-based pathogen reduction process was evaluated against eight viral agents. STUDY DESIGN AND METHODS: Riboflavin and UV light was evaluated against the following eight viral agents: encephalomyocarditis virus (EMC), hepatitis A virus (HAV), hepatitis C virus (HCV), influenza A (FLUAV), La Crosse virus (LACV), pseudorabies virus (PRV), sindbis virus (SINV), and vesicular stomatitis virus (VSV). Before treatment, a sample was removed to determine the product's initial viral load. After treatment the product's viral load was reevaluated and the log reduction was calculated. RESULTS: Virus reduction after treatment with riboflavin and UV light is equivalent in platelet (PLT) and plasma units, as demonstrated by a 3.2-log reduction of EMC in plasma, PLTs, and PLT additive solution containing 35% plasma. Additionally, the following viral reductions values were observed: HAV 1.8 log, HCV at least 4.1 log, FLUAV at least 5.0 log, LACV at least 3.5 log, PRV 2.5 log, SINV 3.2 log, and VSV at least 6.3 log. CONCLUSIONS: The results observed in this study suggest that treating PLT and plasma products with a riboflavin-and-UV-light-based pathogen reduction process could potentially eliminate window period transmission of screened viruses and greatly reduce the risk of transfusion transmission of unscreened viruses.

CoCr wear particles generated from CoCr alloy metal-on-metal hip replacements, and cobalt ions stimulate apoptosis and expression of general toxicology-related genes in monocyte-like U937 cells.

Cobalt-chromium (CoCr) particles in the nanometre size range and their concomitant release of Co and Cr ions into the patients' circulation are produced by wear at the articulating surfaces of metal-on-metal (MoM) implants. This process is associated with inflammation, bone loss and implant loosening and led to the withdrawal from the market of the DePuy ASR™ MoM hip replacements in 2010. Ions released from CoCr particles derived from a resurfacing implant in vitro and their subsequent cellular up-take were measured by ICP-MS. Moreover, the ability of such metal debris and Co ions to induce both apoptosis was evaluated with both FACS and immunoblotting. qRT-PCR was used to assess the effects on the expression of lymphotoxin alpha (LTA), BCL2-associated athanogene (BAG1), nitric oxide synthase 2 inducible (NOS2), FBJ murine osteosarcoma viral oncogene homolog (FOS), growth arrest and DNA-damage-inducible alpha (GADD45A). ICP-MS showed that the wear debris released significant (p<0.05) amounts of Co and Cr ions into the culture medium, and significant (p<0.05) cellular uptake of both ions. There was also an increase (p<0.05) in apoptosis after a 48h exposure to wear debris. Analysis of qRT-PCR results found significant up-regulation (p<0.05) particularly of NOS2 and BAG1 in Co pre-treated cells which were subsequently exposed to Co ions+debris. Metal debris was more effective as an inducer of apoptosis and gene expression when cells had been pre-treated with Co ions. This suggests that if a patient receives sequential bilateral CoCr implants, the second implant may be more likely to produce adverse effects than the first one.

N-(2-Nitro-phen-yl)furan-2-carboxamide.

In the title furan-carboxamide derivative, C11H8N2O4, the benzene and furan rings are rotated from the mean plane of the central fragment by 2.68 (5) and 7.03 (4)°, respectively. The nitro group forms a dihedral angle of 10.15 (5)° with the adjacent benzene ring. In the crystal, mol-ecules are linked by weak C-H⋯O inter-actions, forming helical chains running along [010].

A laboratory comparison of pathogen reduction technology treatment and culture of platelet products for addressing bacterial contamination concerns.

BACKGROUND: Concerns over the risk of bacterial contamination of platelet products have led to implementation of bacteria culture and other screening methods. New approaches for dealing with this issue have also been proposed. STUDY DESIGN AND METHODS: A direct comparison of treatment with riboflavin and ultraviolet (UV) light (Mirasol pathogen reduction technology [PRT] system) versus bacterial culture testing (two-bottle system, 48-hour quarantine) was undertaken to compare their effectiveness. Thirteen clinically relevant bacterial organisms (20 strains) were used in this evaluation. Results were compared with spiking levels at 20 to 100 colony-forming units (CFUs) per product and at less than 20 CFUs per product. RESULTS: At spiking levels of 20 to 100 CFUs per product, the riboflavin and UV light process demonstrated 91% effectiveness against a broad spectrum of bacteria. In comparison, the culture method demonstrated an ability to detect up to 91% of the same contaminants, when used in the two-bottle, 48-hour-to-release configuration. At lower initial titers of contaminating agents (<20 CFUs per product), the effectiveness of PRT increased to 98% whereas the culture method effectiveness decreased to 66%. Effectiveness of the culture method further decreased to 60% when a one-bottle system was used. CONCLUSION: The results from this work suggest that the riboflavin and UV light process may provide up to 98% protection against transfusion of bacterially contaminated units at the most clinically relevant contamination levels (<20 CFUs per product). This compares favorably to the 60% to 66% effectiveness of bacterial culture testing using a 48-hour quarantine period before product release.

(4-Hydr-oxy-2,5-dimethyl-phen-yl)phenyl-methanone.

The title compound, C(15)H(14)O(2), was obtained by Friedel-Crafts acyl-ation between 2,5-dimethyl-phenol and benzoyl chloride in the presence of aluminium chloride as a catalyst. The dihedral angle between the benzene rings is 61.95 (4)°. In the crystal, O-H⋯O hydrogen bonding and C-H⋯O weak inter-actions lead to polymeric C(6), C(8) and C(11) chains along the a, b and c-axis directions, respectively.

Imidazolium 4-amino-benzoate.

In the title salt, C(3)H(5)N(2) (+)·C(7)H(6)NO(2) (-), the carboxyl-ate group of the 4-amino-benzoate anion forms a dihedral angle of 13.23 (17)° with respect to the benzene ring. There are N-H⋯O hydrogen-bonding inter-actions between the anion and cation, and weak inter-molecular C-H⋯O contacts with carboxyl-ate O-atom acceptors of the 4-amino-benzoate anion result in extended three-dimensional R(4) (4)(22) and R(5) (6)(30) edge-fused rings along the [100], [010] and [001] directions.