Kenneth M. Tramposch

Covalently Dye-Linked, Surface-Controlled, and Bioconjugated Organically Modified Silica Nanoparticles as Targeted Probes for Optical Imaging

In this paper we report the synthesis and characterization of organically modified silica (ORMOSIL) nanoparticles, covalently incorporating the fluorophore rhodamine-B, and surface-functionalized with a variety of active groups. The synthesized nanoparticles are of ultralow size (diameter approximately 20 nm), highly monodispersed, stable in aqueous suspension, and retain the optical properties of the incorporated fluorophore. The surface of the nanoparticles can be functionalized with a variety of active groups such as hydroxyl, thiol, amine, and carboxyl. The carboxyl groups on the surface were used to conjugate with various bioactive molecules such as transferrin, as well as monoclonal antibodies such as anti-claudin 4 and anti-mesothelin, for targeted delivery to pancreatic cancer cell lines. In vitro experiments have revealed that the cellular uptake of these bioconjugated (targeted) nanoparticles is significantly higher than that of the nonconjugated ones. The ease of surface functionalization and incorporation of a variety of biotargeting molecules, combined with their observed noncytotoxicity, makes these fluorescent ORMOSIL nanoparticles potential candidates as efficient probes for optical bioimaging, both in vitro and in vivo.

Inhibition of Leukotriene biosynthesis by a novel dietary fatty acid formulation in patients with atopic asthma: A randomized, placebo-controlled, parallel-group, prospective trial

BACKGROUND Leukotriene inhibitors and leukotriene-receptor antagonists are effective in the treatment of inflammatory diseases such as asthma. A search of the entirety of MEDLINE using the terms diet plus leukotrienes identified numerous studies that have explored dietary-management strategies to reduce leukotriene levels through supplementation with polyunsaturated fatty acids such as gamma-linolenic acid (GLA) and eicosapentaenoic acid (EPA). However, the search found no studies on the use of combinations of these fatty acids in patients with asthma. OBJECTIVE The goal of this study was to determine the effect of daily intake of an emulsion (PLT 3514) containing dietary GLA and EPA on ex vivo stimulated whole blood leukotriene biosynthesis in patients with atopic asthma. METHODS This was a randomized, double-blind, placebo-controlled, parallel-group, prospective trial in patients with mild to moderate atopic asthma. Patients consumed 10 g PLT 3514 emulsion (containing 0.75 g GLA + 0.5 g EPA), 15 g PLT 3514 emulsion (containing 1.13 g GLA + 0.75 g EPA), or placebo (olive oil) emulsion daily for 4 weeks. Plasma fatty acids were measured by gas chromatography, and stimulated whole blood leukotrienes were measured by reverse-phase high-performance liquid chromatography with ultraviolet detection using a diode array detector. RESULTS Forty-three patients (33 women, 10 men) participated in the study. Leukotriene biosynthesis was significantly decreased in patients consuming 10 or 15 g PLT 3514 compared with placebo (P < 0.05, analysis of covariance). No clinically significant changes in vital signs were observed throughout the study, and there were no significant between-group differences in treatment-emergent adverse events or mean clinical laboratory values. CONCLUSION Daily consumption of dietary GLA and EPA in a novel emulsion formulation inhibited leukotriene biosynthesis in this population of patients with atopic asthma and was well tolerated.

RADIOIODINE-LABELED AMINES AS BRAIN IMAGING AGENTS

Abstract A series of 125I-labeled 2-hydroxy-5-iodo-benzamides and -benzylamines were synthesized and evaluated as brain imaging agents. The compounds were labeled by a rapid aqueous exchange reaction. This procedure is suitable for kit preparation. Partition coefficients at pH 7.0 and 7,4, protein binding, and biodistribution in rats were studied. Initial brain uptake (2 m after i.v. injection) of the benzylamines was as high as 3,2% of the injected dose, but the benzamides exhibited much lower uptake (~1%). Two compounds N, N-dimethyl-N′-ethyl-N′(2-hydroxy-5-iodo-benzyl)-1,2-ethanediamine and N,N-dimethyl-N′-(2-hydroxy-5-iodobenzyl)-1,3-propanediamine, have biodistributions which indicate potential usefulness as 123I-labeled brain imaging agents.