Eosinophilic responses to stent implantation and the risk of Kounis hypersensitivity associated coronary syndrome

The use of drug eluting stents constitutes a major breakthrough in current interventional cardiology because it is more than halves the need of repeat interventions. It is incontrovertible that coronary stents, in general, have been beneficial for the vast majority of patients. A small increase in thrombosis, following DES implantation, is offset by a diminished risk of complications associated with repeat vascularization. However, late and, especially, very late stent thrombosis is a much feared complication because it is associated with myocardial infarction with increased mortality. Despite that stent thrombosis is thought to be multifactorial, so far clinical reports and reported pathology findings in patients died from coronary stent thrombosis as well as animal studies and experiments, point toward a hypersensitivity inflammation. The stented and thrombotic areas are infiltrated by interacting, via bidirectional stimuli inflammatory cells including eosinophils, macrophages, T-cells and mast cells. Stented regions constitute an ideal surrounding for endothelial damage and dysfunction, together with hemorheologic changes and turbulence as well as platelet dysfunction, coagulation and fibrinolytic disturbances. Drug eluting stent components include the metal strut which contains nickel, chromium, manganese, titanium, molybdenum, the polymer coating and the impregnated drugs which for the first generation stents are: the antimicrotubule antineoplastic agent paclitaxel and the anti-inflammatory, immunosuppressive and antiproliferative agent sirolimus. The newer stents which are called cobalt-chromiun stents and elute the sirolimus analogs everolimus and zotarolimus both contain nickel and other metals. All these components constitute an antigenic complex inside the coronary arteries which apply chronic, continuous, repetitive and persistent inflammatory action capable to induced Kounis syndrome and stent thrombosis. Allergic inflammation goes through three phases, the early phase, the late phase and the chronic phase and these three phases correspond temporally with early (acute and sub acute), late and very late stent thrombosis. Bioabsorbable allergy free poly lactic acid self expanding stents, nickel free stainless steel materials, stent coverage with nitric oxide donors and antibodies with endothelial progenitor cell capturing abilities as well as stents eluting anti-inflammatory and anti-allergic agents might be the solution of this so feared and devastating stent complication.     

Evaluation of Neurofeedback Training in the Treatment of Parkinson's Disease: A Pilot Study

We assess the effects of EEG biofeedback training on levodopa-induced dyskinesia (LID) in patients with Parkinson's disease (PD) using a sham feedback controlled study design. Nine subjects were randomized into either a treatment group or control group and underwent 24 sessions of either active feedback training or sham feedback. The training protocol aimed at increasing 8–15 Hz activity while inhibiting excess 4–8 Hz and 23–34 Hz activity at the C3-C4 derivation. There were no statistically significant differences baseline to post-active neurofeedback training as compared to sham feedback training in primary outcome measures assessing change in dyskinesia severity, nor in secondary outcome measures assessing change in clinical features of PD. Nonsignificant trends were observed in subjects’ PD home diaries indicating a decrease in the severity of motor fluctuations. Baseline to post-training comparisons of secondary outcome measures in quantitative EEG analysis showed significant interaction effects within and between frontal and posterior regions, accompanied by decreases in 25–30 Hz (high beta) relative power, cross spectral power and phase resets per second activity, and significant increases in 8–12 Hz (alpha) relative power, cross spectral power, and coherence activity. These results indicate that EEG biofeedback training can affect the spectral EEG topography of individuals with PD and LID and that training to increase 8–15 Hz activity and decrease 23–34 Hz activity may have been associated with a nonsignificant decrease in dyskinesia severity and an improved sense of well-being.     

Advanced glycation end products and diabetic cardiovascular disease

Advanced glycation end products (AGEs) are formed by a nonenzymatic reaction of sugar moieties (eg, glucose, fructose, glycolytic adducts) with the free amino groups on amino acid residues of proteins. A growing body of data demonstrate that AGEs are intimately involved in the pathophysiology of cardiovascular disease by stimulating inflammation, contributing to atheroma formation, and modulating vascular stiffness. The role of AGEs as potential biomarkers for disease presence and prognosis in patients with diabetes mellitus remains an active area of study. Epidemiologic and angiographic studies suggest that AGE levels may be related to the presence and extent of atherosclerosis, and may predict future outcomes in select populations. The present review summarizes the relevant evidence supporting the role of advanced glycation in promoting atherosclerosis and the epidemiologic studies demonstrating an association between AGEs and diabetic cardiovascular disease.     

Lipoprotein(a) as a Potential Causal Genetic Risk Factor of Cardiovascular Disease: A Rationale for Increased Efforts to Understand its Pathophysiology and Develop Targeted Therapies

Recent published studies have provided increasing evidence that lipoprotein(a) [Lp(a)] may be a potential causal, genetic, independent risk factor for cardiovascular disease (CVD). Lp(a) levels >25 mg/dl are present in ～30% of Caucasians and 60% to 70% of Blacks. Lp(a) is composed of apolipoprotein B-100 and apolipoprotein (a) [(apo(a)]. Circulating Lp(a) levels are primarily influenced by the LPA gene without significant dietary or environmental effects, mediating CVD risk throughout the patient's lifetime. Recent clinical outcomes studies, meta-analyses, and Mendelian randomization studies, in which randomization of Lp(a) levels is achieved through the random assortment of LPA gene variants thereby removing confounders, have shown that genetically determined Lp(a) levels are continuously and linearly related to risk of CVD. Currently, Lp(a) pathophysiology is not fully understood, and specifically targeted therapies to lower Lp(a) are not available. We provide a rationale for increased basic and clinical investigational efforts to further understand Lp(a) pathophysiology and assess whether reducing Lp(a) levels minimizes CVD risk. First, a detailed understanding of Lp(a) synthesis and clearance has not been realized. Second, several mechanisms of atherogenicity are known to varying extent, but the relative contributions of each are not known. Lp(a) may be atherothrombotic through its low-density lipoprotein moiety, but also through apo(a), including its ability to be retained in the vessel wall and mediate pro-inflammatory and proapoptotic effects including those potentiated by its content of oxidized phospholipids, and antifibrinolytic effects. Finally, development of specific Lp(a)-lowering agents to potently lower Lp(a) will allow testing of mechanistic hypotheses in animal models and the design of randomized clinical trials to assess reduction in CVD. A convergence of academic, scientific, pharmaceutical, and National Institutes of Health priorities and efforts can make this a reality in the next decade.