Heart Failure Pharmacogenetics: Past,Present, and Future

Heart failure is an increasingly common disease associated with significant morbidity and mortality in the aging population. Recent advances in heart failure pharmacotherapy have established several agents as beneficial to disease progression and outcomes. However, current consensus guideline-recommended pharmacotherapy may not represent an optimal treatment strategy in all heart failure patients. Specifically, individuals with genetic variation in regions central to mediation of beneficial response to standard heart failure agents may not receive optimal benefit from these drugs. Additionally, targeted approaches in phase 3 clinical trials that select patients for inclusion based on the genotype most likely to respond might advance the currently stalled drug development pipeline in heart failure. This article reviews the literature in heart failure pharmacogenetics to date, opportunities for discovery in recent and upcoming clinical trials, as well as future directions in this field.     

Immune Modulation in Heart Failure: Past Challenges and Future Hopes

Immune-modulation therapy has had great success in various inflammatory diseases. Despite the promising results of preliminary studies in anti-tumor necrosis factor-α therapies, large randomized studies have lacked positive clinical outcomes in patients with heart failure. These results have led to the idea that therapies directed toward specific inflammatory mediators may not be the answer and lead us toward the development of novel anti-inflammatory strategies that may involve a broader spectrum of inflammatory mediators. Therapeutic plasma exchange has been demonstrated as a safe treatment, and preliminary outcomes led us to develop new treatment schemes.     

Cytokines: Past, Present, and Future

This review provides an historical account of the discovery and development of cytokines. Cytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell growth, differentiation, cell death, angiogenesis, and development and repair processes aimed at the restoration of homeostasis. Although cytokines are occasionally produced constitutively, they are usually produced by virtually every nucleated cell type in response to injurious stimuli. Cytokines act on cells expressing complementary receptors. Cytokines have been assigned to various family groups based on the structural homologies of their receptors. This review shows how cytokine research evolved from phenomenological to molecular stages and from a focus on ligands to characterization of cytokine receptors. The advent of molecular biology, monoclonal antibodies, and microsequencing made it possible to obtain pure recombinant cytokine preparation for experimental and therapeutic applications. The development of targeted gene deletions revealed many cytokines to have unexpected pathophysiological functions. The identification of "virokines," homologues that mimic cytokine ligands and receptors, has provided impetus to the founding of biotechnology companies aimed at developing cytokine agonists and antagonists for therapeutic applications. The discipline of cytokinology is now endowed with several journals, multiple annual meetings, and many devoted investigators. The explosion in cytokine information over the past 40 years has been enormous and full of surprises. If past be prologue, with the advent of genomics and proteomics the future should witness even greater progress.     

弓形虫研究的过去、现在与未来

弓形虫为顶复动物门寄生原虫,呈世界性广泛分布,可感染所有温血动物,并在宿主免疫功能低下或受抑制时导致严重的疾患,其极高的流行性和致病的机会性已越来越引起人们的关注。本文回顾了弓形虫研究的历史,综述了目前弓形虫研究的热点并提出了在今后研究中需要解决的问题。     

Swine Norovirus: Past,Present, and Future

Norovirus, an ssRNA + virus of the family Caliciviridae, is a leading disease burden in humans worldwide, causing an estimated 600 million cases of acute gastroenteritis every year. Since the discovery of norovirus in the faeces of swine in Japan in the 1990s, swine norovirus has been reported in several countries on several continents. The identification of the human-associated GII.4 genotype in swine has raised questions about this animal species as a reservoir of norovirus with zoonotic potential, even if species-specific P-types are usually detected in swine. This review summarises the available data regarding the geographic distribution of norovirus in swine, the years of detection, the genotype characterisation, and the prevalence in specific production groups. Furthermore, we discuss the major bottlenecks for the detection and characterisation of swine noroviruses.     

Multi-Bed Vascular Disease: Past,Present, and Future

Journal of Thrombosis and Thrombolysis -     

Peripheral Artery Disease: Past,Present, and Future

Peripheral artery disease is a prevalent but underdiagnosed manifestation of atherosclerosis. There is insufficient awareness of its clinical manifestations, including intermittent claudication and critical limb ischemia and of its risk of adverse cardiovascular and limb outcomes. In addition, our inadequate knowledge of its pathophysiology has also limited the development of effective treatments, particularly in the presence of critical limb ischemia. This review aims to highlight essential elements of the epidemiology and pathophysiology of peripheral artery disease, bring attention to the often-atypical manifestations of occlusive arterial disease of the lower extremity, increase awareness of critical limb ischemia, briefly describe the diagnostic role of the ankle brachial index, and go over the contemporary management of peripheral artery disease. An emphasis is placed on evidence-based medical treatments to improve symptoms and quality of life and to reduce the risk of cardiovascular and limb events in these patients, including supervised exercise training, smoking cessation, antagonism of the renin-angiotensin system, lipid-lowering, antiplatelet, and antithrombotic therapies.     

Carotid Baroreflex Activation: Past,Present, and Future

Electrical activation of the carotid baroreceptor system is an attractive therapy for the treatment of resistant hypertension. In the past, several attempts were made to directly activate the baroreceptor system in humans, but the method had to be restricted to a few selected patients. Adverse effects, the need for better electrical devices and better surgical techniques, and the lack of knowledge about long-term effects has greatly hampered developments in this area for many years. Recently, a new and promising device was evaluated in a multicenter feasibility trial, which showed a clinically and statistically significant reduction in office systolic blood pressure (>20 mm Hg). This reduction could be sustained for at least 2 years with an acceptable safety profile. In the future, this new device may stimulate further application of electrical activation of the carotid baroreflex in treatment-resistant hypertension.