Novel Targets for Old and Diseased Hearts

In this Special Issue we cover a selection of original articles and reviews devoted to the definition of novel molecular targets in cardiovascular diseases, which not only deepen our knowledge on the pathogenesis of the diseases under study, but potentially pave the way to novel diagnostic tools and therapeutic approaches [...]

Biologics and cardiac disease: challenges and opportunities

Biologics are revolutionizing the treatment of chronic diseases, such as cancer and monogenic disorders, by overcoming the limits of classic therapeutic approaches using small molecules. However, the clinical use of biologics is limited for cardiovascular diseases (CVDs) , which are the primary cause of morbidity and mortality worldwide. Here, we review the state-of-the-art use of biologics for cardiac disorders and provide a framework for understanding why they still struggle to enter the field. Some limitations are common and intrinsic to all biological drugs, whereas others depend on the complexity of cardiac disease. In our opinion, delineating these struggles will be valuable in developing and accelerating the approval of a new generation of biologics for CVDs

Emerging treatment options for refractory angina pectoris: ranolazine, shock wave treatment, and cell-based therapies.

Abstract A challenge of modern cardiovascular medicine is to find new, effective treatments for patients with refractory angina pectoris, a clinical condition characterized by severe angina despite optimal medical therapy. These patients are not candidates for surgical or percutaneous revascularization. Herein we review the most up-to-date information regarding the modern approach to the patient with refractory angina pectoris, from conventional medical management to new medications and shock wave therapy, focusing on the use of endothelial precursor cells (EPCs) in the treatment of this condition. Clinical limitations of the efficiency of conventional approaches justify the search for new therapeutic options. Regenerative medicine is considered the next step in the evolution of organ replacement therapy. It is driven largely by the same health needs as transplantation and replacement therapies, but it aims further than traditional approaches, such as cell-based therapy. Increasing knowledge of the role of circulating cells derived from bone marrow (EPCs) on cardiovascular homeostasis in physiologic and pathologic conditions has prompted the clinical use of these cells to relieve ischemia. The current state of therapeutic angiogenesis still leaves many questions unanswered. It is of paramount importance that the treatment is delivered safely. Direct intramyocardial and intracoronary administration has demonstrated acceptable safety profiles in early trials, and may represent a major advance over surgical thoracotomy. The combined efforts of bench and clinical researchers will ultimately answer the question of whether cell therapy is a suitable strategy for treatment of patients with refractory angina

Sensitive and quantitative method to evaluate DNA methylation of the positive regulatory domains (PRDI, PRDII) and cAMP response element (CRE) in human endothelial nitric oxide synthase promoter.

Nitric oxide plays a prominent role in the cardiovascular system and much attention has been devoted in the last years on deciphering the regulation of human endothelial nitric oxide synthase (eNOS) expression. Epigenetic-based mechanisms have a key role in the eNOS expression and their pathologic perturbations may have profound effects on the steady state RNA levels in the endothelium. The human eNOS promoter lacks a canonical TATA box and it does not contain a proximal CpG island. A differentially DNA methylated region (DMR) in the native eNOS proximal promoter is involved in gene expression regulation. Here we describe a quantitative, sensitive and cost-effective method that, relying on a novel normalization strategy, allows the quantification of DNA methylation status of the positive regulatory domains (PRDI, PRDII) and cAMP response element (CRE) in human eNOS promoter. This technique will enable to explore the functional relevance of DNA methylation perturbations of eNOS promoter both under pathological and physiological conditions

Recent advances in managing human papillomavirus-positive oropharyngeal tumors

Human papillomavirus (HPV) is detected in a subset of patients with head and neck squamous cell carcinoma, most frequently in tumors in the Waldeyer's ring (palatine tonsil and base of tongue). Several studies suggest that patients with HPV-positive tumors have better survival with either concurrent chemoradiation therapy or surgery followed by radiation compared with HPV-negative patients. However, some possible confounding clinicopathologic variables may challenge the validity of this statement, for example, some authors used the TNM (tumor, node, metastasis) grouping stage while others used the primary tumor (T stage), and other studies have demonstrated that tumors with advanced T stage were less likely to be infected with HPV. A large clinical trial with stratification of patients according to all known tumor prognostic factors is crucial to solve the question

Innovative monitoring of atmospheric gaseous hydrogen fluoride

Hydrogen fluoride (HF) is a basic raw material for a wide variety of industrial products, with a worldwide production capacity of more than three million metric tonnes. A novel method for determining particulate fluoride and gaseous hydrogen fluoride in air is presented herewith. Air was sampled using miniaturised 13 mm Swinnex two-stage filter holders in a medium-flow pumping system and through the absorption of particulate fluoride and HF vapours on cellulose ester filters uncoated or impregnated with sodium carbonate. Furthermore, filter desorption from the holders and the extraction of the pentafluorobenzyl ester derivative based on solid-phase microextraction were performed using an innovative robotic system installed on an xyz autosampler on-line with gas chromatography (GC)/mass spectrometry (MS). After generating atmospheres of a known concentration of gaseous HF, we evaluated the agreement between the results of our sampling method and those of the conventional preassembled 37 mm cassette (±8.10%; correlation coefficient: 0.90). In addition, precision (relative standard deviation for n=10, 4.3%), sensitivity (0.2 μg/filter), and linearity (2.0–4000 μg/filter; correlation coefficient: 0.9913) were also evaluated. This procedure combines the efficiency of GC/MS systems with the high throughput (96 samples/day) and the quantitative accuracy of pentafluorobenzyl bromide on-sample derivatisation

Regenerative Therapy in Peripheral Artery Disease

Patients with peripheral artery disease (PAD) and critical limb ischemia are the main candidates for limb amputations and have a poor life expectancy. Frequently, these patients are not eligible for either surgical or percutaneous interventions aimed at mechanical revascularization. Therefore, new strategies need to be identified to offer these patients a viable therapeutic option. Gene and cell therapy hold great promise for the treatment of peripheral vascular diseases because, in animal models, local delivery of growth factors and endothelial progenitor cells result in new blood vessel formation and regeneration of ischemic tissues. In this article, are reviewed phase I and phase II gene, and cell therapy clinical trials in patients with PAD

development of an innovative gas chromatography mass spectrometry method for assessment of formaldehyde in the workplace atmosphere

World consumption of formaldehyde (FA) is forecast to grow at an average annual rate of about 4% from 2015 to 2020 with world production to exceed 52 million tons in 2017. From the first day of January 2016, the Commission Regulation No. 91/2015 established the FA classification through an indication from European Chemical Agency as category 2 mutagenic and category 1B carcinogen. A novel method for the determination of gaseous FA in air is presented herewith. The sampling was carried out using a miniaturized cartridge by means of a medium-flow pumping system (1.0 L min-1, 5–60 min) and absorption of FA vapors on 2,4-dinitrophenylhydrazine. Cartridge desorption removing the excess derivatizing agent based upon solid-phase extraction was performed by an innovative xyz robotic system on-line with fast gas chromatography (GC)—mass spectrometry (MS). Through the generation of standard atmospheres of known concentration of FA, we evaluated the precision (relative standard deviation for n = 10, 8.8%), lower lim..