Emerging Therapies for Acute Coronary Syndromes

In the majority of cases acute coronary syndromes (ACS) are caused by activation and aggregation of platelets and subsequent thrombus formation leading to a decrease in coronary artery blood flow. Recent focus on the treatment of ACS has centered on reducing the response of platelets to vascular injury as well as inhibiting fibrin deposition. Novel therapies include more effective P2Y12 receptor blockers thereby reducing inter-individual variability, targeting the platelet thrombin receptor (protease activated receptor 1) as well as directly inhibiting factor Xa or thrombin activity. In this review we discuss the clinical data evaluating the effectiveness of these various new ACS treatment options

An Ultra-Thin Polymer Coating for the Tethering of Adenoviral Vector to the Surface of Coronary Stents

Our group has previously demonstrated stent-based gene delivery with either viral or plasmid vectors. However, these previous studies utilized bulky PLGA or collagen stent coatings, known to cause inflammatory reactions in stented arteries. In the present experiments we successfully attached adenoviruses either directly, or via anti-adenovirus antibodies to the steel surface of stents using chemical coordination with biphosphonates

Cultivating Forgiveness and Compassion Through a Mindfulness-based Program for Teachers: Results from Two Field Interventions

The aim of this research was to determine if a mindfulness-training (MT) program for teachers cultivated habits of mind (e.g., mindfulness, emotion regulation, compassion and forgiveness) conducive to effective teaching. Data were gathered in two randomized control trials. Results from pre- to post-test and follow-up showed that MT was associated with increases in mindfulness, efficacy for regulating emotion on the job, and the tendency to forgive others. Linguistic analyses revealed that teachers who underwent MT expressed more positive affect when discussing their most challenging student than those in the waitlist control group. Results warrant further investigation using behavioral-, observational-, and third-person measures of these habits of mind in the target individual

Cultivating Forgiveness and Compassion Through a Mindfulness-based Program for Teachers: Results from Two Field Interventions

The aim of this research was to determine if a mindfulness-training (MT) program for teachers cultivated habits of mind (e.g., mindfulness, emotion regulation, compassion and forgiveness) conducive to effective teaching. Data were gathered in two randomized control trials. Results from pre- to post-test and follow-up showed that MT was associated with increases in mindfulness, efficacy for regulating emotion on the job, and the tendency to forgive others. Linguistic analyses revealed that teachers who underwent MT expressed more positive affect when discussing their most challenging student than those in the waitlist control group. Results warrant further investigation using behavioral-, observational-, and third-person measures of these habits of mind in the target individual

Biphosphonate-Mediated Gene Vector Delivery from the Metal Surfaces of Stents

The clinical use of metallic expandable intravascular stents has resulted in imporved therapeutic outcomes for coronary artery disease. However, arterial reobstruction after stenting, in-stent restenosis, remains an important problem. Gene therapy to treat in-stent restenosis by using gene vector delivery from the metallic stent surfaces has never been demonstrated. The present studies investigated the hypothesis that metal-biphosphonate binding can enable site-specific gene vector delivery from metal surfaces. Polyallylamine biphosphonate (PAA-BP) was synthesized by using Michael addition methodology. Exposure to aqueous solutions of PAA-BP resulted in the formation of a monomolecular biphosphonate later on metal alloy surfaces (steel, nitinol, and cobalt-chromium), as demonstrated by x-ray photoelectron spectroscopy. Surface-bound PAA-BP enabled adenoviral (Ad) tethering due to covalent thiol-binding of either anti-Ad antibody or a recombinant Ad-receptor protein, D1. In arterial smooth muscle cell cultures, alloy samples configured with surface-tethered Ad were demonstrated to achieve site-specific transduction with a reporter gene, (GFP). Rat carotid stent angioplasties using metal stents exposed to aqueous PAA-BP and derivatized with anti-knob antibody or D1 resulted in extensive localized Ad-GFP expression in the arterial wall. In a separate study with a model therapeutic vector, Ad-inducible nitric oxide synthase (iNOS) attached to the biphosphonate-treated metal stent surface via D1, significant inhibition of restenosis was demonstrated (neointimal/media ration 1.68 ± 0.27 and 3.4 ± 0.35; Ad-iNOS vs. control, P \u3c 0.01). Is is concluded that effective gene vector delivery from metallic stent surfaces can be achieved using this approach