Cell Membrane Modification for Rapid Display of Bi-Functional Peptides: A Novel Approach to Reduce Complement Activation

Ischemia and reperfusion of organs is an unavoidable consequence of transplantation. Inflammatory events associated with reperfusion injury are in part attributed to excessive complement activation. Systemic administration of complement inhibitors reduces reperfusion injury but leaves patients vulnerable to infection. Here, we report a novel therapeutic strategy that decorates cells with an anti-complement peptide. An analog of the C3 convertase inhibitor Compstatin (C) was synthesized with a hexahistidine (His6) tag to create C-His6. To decorate cell membranes with C-His6, fusogenic lipid vesicles (FLVs) were used to incorporate lipids with nickel (Ni2+) tethers into cell membranes, and these could then couple with C-His6. Ni2+ tether levels to display C-His6 were modulated by changing FLV formulation, FLV incubation time and FLV levels. SKOV-3 cells decorated with C-His6 effectively reduced complement deposition in a classical complement activation assay. We conclude that our therapeutic approach appears promising for local ex vivo treatment of transplanted organs to reduce complement-mediated reperfusion injury

Rapidly Resolving Nonalcoholic Marchiafava-Bignami Disease in the Setting of Malnourishment After Gastric Bypass Surgery

Objectives. We describe a rare case of nonalcoholic Marchiafava-Bignami disease (MBD) in the setting of malnourishment after gastric bypass. Methods. A 44-year-old nonalcoholic Caucasian woman with malnutrition after gastric bypass presented with 2 weeks of weakness. The patient acutely became stuporous. Brain magnetic resonance imaging showed lesions in the corpus callosum and internal capsules consistent with MBD. After 10 days of treatment, the patient had resolution of her encephalopathy with return to baseline mental function, with radiological improvement. Results. MBD is a rare neurological disorder seen in alcoholics and can rapidly progress to coma or death. Our patient was successfully treated with a regimen typically used in alcoholics. We discuss the relevant literature supporting this regimen. Conclusions. This case demonstrates that since the pathophysiological etiology of the disease is malnutrition, MBD patients can be effectively treated with this regimen regardless of the underlying cause