Pharmacologic targeting of renal ischemia-reperfusion injury using a normothermic machine perfusion platform.

Normothermic machine perfusion (NMP) is an emerging modality for kidney preservation prior to transplantation. NMP may allow directed pharmacomodulation of renal ischemia-reperfusion injury (IRI) without the need for systemic donor/recipient therapies. Three proven anti-IRI agents not in widespread clinical use, CD47-blocking antibody (αCD47Ab), soluble complement receptor 1 (sCR1), and recombinant thrombomodulin (rTM), were compared in a murine model of kidney IRI. The most effective agent was then utilized in a custom NMP circuit for the treatment of isolated porcine kidneys, ascertaining the impact of the drug on perfusion and IRI-related parameters. αCD47Ab conferred the greatest protection against IRI in mice after 24 hours. αCD47Ab was therefore chosen as the candidate agent for addition to the NMP circuit. CD47 receptor binding was demonstrated by immunofluorescence. Renal perfusion/flow improved with CD47 blockade, with a corresponding reduction in oxidative stress and histologic damage compared to untreated NMP kidneys. Tubular and glomerular functional parameters were not significantly impacted by αCD47Ab treatment during NMP. In a murine renal IRI model, αCD47Ab was confirmed as a superior anti-IRI agent compared to therapies targeting other pathways. NMP enabled effective, direct delivery of this drug to porcine kidneys, although further efficacy needs to be proven in the transplantation setting

Hazard Analysis for Cesium Shipments

The rail shipment of large quantities of radiocesium involves a potential accidental release of this material in a readily available form to the biosphere. The magnitude of the associated potential damage to man and his environment is evaluated in this report. The evaluation of the consequences of an accidental release of Cs-137 from the Shielded Transfer Tank, Model II (STT) assumes loss of Cs-137 to the atmosphere or to surface-water. Release to the atmosphere could result from a collision followed by fire or explosion. In the event of a fire, a small fraction of the Cs-137 vould be volatilized. An explosion would disperse the Cs-137 still adsorbed to Decalso as particulates. In either case, the material is assumed to be dispersed by atmospheric mechanisms which can be described by modified Sutton equations. The accident involving a fire or explosion assumes that 1 percent or 10 percent, respectively, of 90,000 curies of Cs-137 is dispersed in a metropolitan area. Contamination of the surrounding suburban area is also involved. Damage estimates amount to about 60 million dollars and 400 million dollars, corresponding to a 1 percent and a 10 percent release respectively. Another possible type of accident involves the release of the Decalso (an inorganic ion exchange carrier for the cesium) into a river. However, the release of Cs-137 by elution into the river results in minor damage compared to the atmospheric release cases