Local lentiviral short hairpin RNA silencing of CCR2 inhibits vein graft thickening in hypercholesterolemic apolipoprotein E3-Leiden mice

Objective: Inflammatory responses to vascular injury are key events in vein graft disease and accelerated atherosclerosis, which may result in bypass failure. The monocyte chemoattractant protein-1 (MCP-1)/CC-chemokine receptor (CCR)-2 pathway is hypothesized to play a central role. A murine model for vein graft disease was used to study the...

Transdermal administration of radiolabelled [14C]rotigotine by a patch formulation: A mass balance trial

Background and objective: The dopamine agonist rotigotine has been formulated in a silicone-based transdermal system for once-daily administration. The objective of the present study was to characterise the mass balance of rotigotine in humans after administration of a single transdermal patch containing radiolabelled [14C]rotigotine and to...

Activation of nuclear receptor Nur77 by 6-mercaptopurine protects against neointima formation

BACKGROUND - Restenosis is a common complication after percutaneous coronary interventions and is characterized by excessive proliferation of vascular smooth muscle cells (SMCs). We have shown that the nuclear receptor Nur77 protects against SMC-rich lesion formation, and it has been demonstrated that 6-mercaptopurine (6-MP) enhances Nur77...

Local cre-mediated gene recombination in vascular smooth muscle cells in mice

Here we describe a means to conditionally modify genes at a predefined and localized region of the vasculature using a perivascular drug delivery device (PDD). A 4-hydroxytamoxifen (4-OHT)-eluting PDD was applied around the carotid or femoral artery of a mouse strain carrying both the tamoxifen-inducible and smooth muscle cell (SMC)-specific Cre...

Drug-eluting stents studies in mice: Do we need atherosclerosis to study restenosis?

In 2001, the first human study with drug-eluting stents (DES) was published showing a nearly complete abolition of restenosis by using a sirolimus-eluting stent. This success was very encouraging to test new compounds in combination with the DES platform. Nevertheless, several other anti-restenotic compounds have been used in human clinical...

Tumor necrosis factor-α plays an important role in restenosis development

Genetic factors appear to be important in the restenotic process after percutaneous coronary intervention (PCI), as well as in inflammation, a pivotal factor in restenosis. TNFα, a key regulator of inflammatory responses, may exert critical influence on the development of restenosis after PCI. The GENetic DEterminants of Restenosis (GENDER)...

Local perivascular delivery of anti-restenotic agents from a drug-eluting poly(ε-caprolactone) stent cuff

The introduction of drug-eluting stents (DES) to prevent in-stent restenosis is one of the major advances in interventional cardiology. Currently many types of DES are under evaluation for effectiveness and safety, a time-consuming and difficult procedure in humans. An animal model that allows rapid evaluation of the present and upcoming...

A dynamic artificial gastrointestinal system for studying the behavior of orally administered drug dosage forms under various physiological conditions

Purpose. The purpose of this study was to demonstrate the potential of a dynamic, multicompartmental in vitro system simulating the human stomach and small intestine (TIM-1) for studying the behavior of oral drug dosage forms under various physiological gastrointestinal conditions. Methods. Two model drug compounds were studied in TIM-1: a...

The production of antibody fragments and antibody fusion proteins by yeasts and filamentous fungi

In this review we will focus on the current status and views concerning the production of antibody fragments and antibody fusion proteins by yeasts and filamentous fungi. We will focus on single-chain antibody fragment production (scFv and VHH) by these lower eukaryotes and the possible applications of these proteins. Also the coupling of...

Lactobacilli as live vaccine delivery vectors: Progress and prospects

Evidence is accumulating that lactobacilli influence the immune response in a strain-dependent manner. This immunomodulatory capacity is important for the development of the immune response, and also identifies Lactobacillus as a potent oral vaccine carrier. Most of our current knowledge of the use of lactobacilli for vaccination purposes has...

Polylysine as a vehicle for extracellular matrix-targeted local drug delivery, providing high accumulation and long-term retention within the vascular wall

We present the first steps in the elaboration of an approach of extracellular matrix-targeted local drug delivery (ECM-LDD), designed to provide a high concentration, ubiquitous distribution, and long-term retention of a drug within the vessel wall after local intravascular delivery. The approach is based on the concept of a bifunctional drug...

Human safety and pharmacokinetics of the CFC alternative propellants HFC 134a (1,1,1,2-tetrafluoroethane) and HFC 227 (1,1,1,2,3,3,3-heptafluoropropane) following whole-body exposure

HFC 134a (1,1,1,2-tetrafluoroethane) and HFC 227 (1,1,1,2,3,3,3-heptafluoropropane) are used to replace chlorofluorocarbons (CFCs) in refrigerant and aerosol applications, including medical use in metered-dose inhalers. Production and consumption of CFCs are being phased out under the Montreal Protocol on Substances that Deplete the Ozone Layer....

Live bacterial delivery systems for development of mucosal vaccines

By expression of foreign antigens in attenuated strains derived from bacterial pathogens and in non-pathogenic commensal bacteria, recombinant vaccines are being developed that aim to stimulate mucosal immunity. Recent advances in the pathogenesis and molecular biology of these bacteria have allowed rational development of new and improved...

Lactic acid bacteria as antigen delivery vehicles for oral immunization purposes

In vaccination programmes in which large numbers of subjects are involved, the oral route of administration is more convenient as compared to the more frequently used parenteral route. This is particularly relevant when vaccines are to be applied in less industrialized countries. Lactic acid bacteria in general and strains of Lactobacillus in...