An in vitro Model System for Evaluating Remote Magnetic Nanoparticle Movement and Fibrinolysis.

BACKGROUND: Thrombotic events continue to be a major cause of morbidity and mortality worldwide. Tissue plasminogen activator (tPA) is used for the treatment of acute ischemic stroke and other thrombotic disorders. Use of tPA is limited by its narrow therapeutic time window, hemorrhagic complications, and insufficient delivery to the location of the thrombus. Magnetic nanoparticles (MNPs) have been proposed for targeting tPA delivery. It would be advantageous to develop an improved in vitro model of clot formation, to screen thrombolytic therapies that could be enhanced by addition of MNPs, and to test magnetic drug targeting at human-sized distances. METHODS: We utilized commercially available blood and endothelial cells to construct 1/8th inch (and larger) biomimetic vascular channels in acrylic trays. MNP clusters were moved at a distance by a rotating permanent magnet and moved along the channels by surface walking. The effect of different transport media on MNP velocity was studied using video photography. MNPs with and without tPA were analyzed to determine their velocities in the channels, and their fibrinolytic effect in wells and the trays. RESULTS: MNP clusters could be moved through fluids including blood, at human-sized distances, down straight or branched channels, using the rotating permanent magnet. The greatest MNP velocity was closest to the magnet: 0.76 ± 0.03 cm/sec. In serum, the average MNP velocity was 0.10 ± 0.02 cm/sec. MNPs were found to enhance tPA delivery, and cause fibrinolysis in both static and dynamic studies. Fibrinolysis was observed to occur in 85% of the dynamic MNP + tPA experiments. CONCLUSION: MNPs hold great promise for use in augmenting delivery of tPA for the treatment of stroke and other thrombotic conditions. This model system facilitates side by side comparisons of MNP-facilitated drug delivery, at a human scale.

A 1-day imported fire ant rush immunotherapy schedule with and without premedication.

BACKGROUND: Rush immunotherapy (RIT) schedules can expedite protection in individuals sensitive to imported fire ant (IFA) stings. OBJECTIVE: To evaluate the safety and efficacy of 1-day RIT with IFA whole body extract (WBE) and determine the benefit of premedication with antihistamines and prednisone. METHODS: Patients with systemic reactions to IFAs and evidence of specific IgE by skin test or serologic test started a 1-day RIT protocol without premedication. The 1-day RIT protocol consisted of a total of 10 injections every 30 to 60 minutes to achieve a 0.3-mL 1:100 (wt/vol) dose. A higher systemic reaction rate (SRR) prompted protocol revision to include a 3-day course of oral 20 mg of prednisone twice daily, 150 mg of ranitidine, and 10 mg of loratadine started 2 days before the 1-day RIT. Patients returned on days 8 and 15 to receive a 0.5 mL 1:100 (wt/vol) maintenance injection. The effectiveness of the RIT was evaluated with a sting challenge on approximately day 22. RESULTS: Eighty of the 96 patients enrolled initiated the 1-day RIT. The first nonpremedicated group exhibited a SRR of 24.3% (9 of 37 patients), whereas the revised premedicated group had a SRR of 9.5% (4 of 42 patients; P = .07). The most severe reaction during RIT included dizziness, angioedema, and urticaria. Sting challenges on 53 patients resulted in 1 mild rhinitis reaction (efficacy, 98.1%). CONCLUSION: One-day RIT with IFA WBE for IFA hypersensitivity is efficacious. Although there was a trend with premedications to reduce SRRs during the RIT, safety data with premedication require confirmation in a larger trial.

Seal and whale meat: two newly recognized food allergies.

BACKGROUND: Alaska's marine mammals compose a large portion of the diet of indigenous coastal Alaskan people. Bowhead whales (Balaena mysticetus) and bearded seals (Erignathus barbatus), inhabitants of the Bering and Beaufort seas along Alaska's western and northern coasts, are 2 of the most important subsistence species, serving as major food sources to the native population. OBJECTIVE: To describe an Inupiaq boy with symptoms consistent with an IgE-mediated food allergy after ingestion of bowhead whale and bearded seal meat. METHODS: Extracts of cooked bowhead whale and bearded seal were prepared, lyophilized, and evaluated for protein content. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was performed for each extract, followed by transfer to nitrocellulose and IgE immunoblots. Skin prick testing was conducted using reconstituted extracts of 1:10 wt/vol dilution. RESULTS: Immunoblots revealed serum specific IgE binding with the extracts of bowhead whale and bearded seal meat. Protein bands of approximately 25, 40, 50, and 90 kDa were found in the seal meat. Protein bands of 55 and 90 kDa were found in the whale meat. Skin prick test results were positive to whale and seal extracts with appropriate positive and negative controls. Ten control subjects had negative reactions to both extracts. CONCLUSION: A patient with moderate anaphylaxis to bowhead whale and bearded seal meat demonstrated serum specific IgE by means of immunoblot and positive skin prick test results. This is the first known reported case of specific IgE to these species.