Ultrasound-based molecular imaging and specific gene delivery to mesenteric vasculature by endothelial adhesion molecule targeted microbubbles in a mouse model of Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract (GI) for which treatments with immunosuppressive drugs have significant side-effects. Consequently, there is a clinical need for site-specific and non-toxic delivery of therapeutic genes or drugs for CD and related disorders such as inflammatory bowel disease. The aim of this study was to validate a gene delivery platform based on ultrasound-activated lipid-shelled microbubbles (MBs) targeted to inflamed mesenteric endothelium in the CD-like TNFΔARE mouse model.

Nanobody-coupled microbubbles as novel molecular tracer.

Camelid-derived single-domain antibody-fragments (~15kDa), called nanobodies, are a new class of molecular tracers that are routinely identified with nanomolar affinity for their target and that are easily tailored for molecular imaging and drug delivery applications. We hypothesized that they are well-suited for the design of targeted microbubbles (μBs) and aimed to develop and characterize eGFP- and VCAM-1-targeted μBs. Anti-eGFP (cAbGFP4) and anti-VCAM-1 (cAbVCAM1-5) nanobodies were site-specifically biotinylated in bacteria.

Ultrasound-triggered release of materials entrapped in microbubble-liposome constructs: a tool for targeted drug delivery.

We investigated the preparation of ultrasound-triggered drug delivery system, based on a pendant complex of microbubble coated with liposomes. Biotinylated decafluorobutane microbubbles were coated with biotinylated liposomes via a streptavidin linker. Liposomes were prepared incorporating calcein and thrombin.

High-threshold, Kv3-like potassium currents in magnocellular neurosecretory neurons and their role in spike repolarization.

We identified Kv3-like high-threshold K+ currents in hypothalamic supraoptic neurons using whole cell recordings in hypothalamic slices and in acutely dissociated neurons. Tetraethylammonium (TEA)-sensitive currents (< 1 mM TEA) evoked from -50 mV were characterized by a large component that inactivated in 10-30 ms, and a smaller, persistent component that inactivated in 1-2 s. I/V relations in dissociated neurons revealed TEA-subtracted currents with a slope and voltage dependency consistent with the presence of Kv3-like channels.

AHP's, HAP's and DAP's: how potassium currents regulate the excitability of rat supraoptic neurones.

We have constructed mathematical models of the electrical activity of two hypothalamic supraoptic neuro-secretory cell-types, and we support our models with new calcium imaging and in vitro electrophysiological data. These cells are neurones that project to the pituitary gland and secrete either of two hormones, oxytocin or vasopressin, into the blood from their axonal terminals. Oxytocin-secreting and vasopressin-secreting cells are closely related and physically they differ only subtly, however when physiologically stressed their discharge patterns are dramatically distinct.