Vascular regulation of endogenous fibrinolysis in man

The initiation, modulation and resolution of thrombus associated with eroded or unstable coronary plaques are critical determinants of acute coronary events. This itself is dependent on the cellular function of the surrounding endothelium and vascular wall. In particular, the regulation of vascular tone and the acute release of tissue plasminogen activator by the endothelium make important contributions to the defence against intravascular thrombosis. These aspects of endothelial function will provide major new insights into the pathophysiology of cardiovascular disease, and to shape future therapeutic interventions.The experimental medicine models presented here originate from an early interest in exploring these novel aspects of endothelial function, and in particular, the acute release of the endothelium-derived fibrinolytic factor, tissue plasminogen activator. This model was initiated, developed and applied to a diverse range of physiological and pathophysiological circumstances that have informed health and disease. Publications are grouped into 5 main sections.Section 1 describes the early validation and exploration of the model to stimulate acute tissue plasminogen activator release using a variety of physiological and pathophysiological mediators. This describes the early identification of potent stimulators of acute tissue plasminogen activator release including substance P, bradykinin, desmopressin and thrombin receptor agonists. This work was extended to demonstrate the important role of nitric oxide and vascular inflammation in this process. Subsequent sections cover the application of these techniques in patient populations with a predisposition to cardiovascular disease (Section 2) as well as with established (Section 3) and end-stage disease (Section 4). These sections also explore the potentially important modulation of the renin-angiotensin system with particular reference to angiotensin-converting enzyme inhibition and the role of bradykinin. Section 5 contains some miscellaneous work and reviews of the subject area bring together the key aspects of the field as well as an important study to address the vascular endothelial function in patients with a rare haematological deficiency, type 3 von Willebrand disease

Ocular and systemic vascular alterations in overweight and obese individuals undergoing weight-loss interventions

Obesity and its accompanying comorbidities play a crucial role in the pathogenesis of endothelial function which is a pre-cursor to atherosclerosis, subsequently leading to increases in cardiovascular risk. However, amelioration of these risk factors and improvements in endothelial function have never been fully explored in functional assessments of the retinal and peripheral microcirculations.The aim of this thesis was therefore to investigate the presence and impact of weight-loss interventions in overweight and obese individuals and also the relationships between functional measurements of different vascular beds. The principle findings of this work were:1. The relationship between retinal and peripheral vascular function in healthy individuals with low cardiovascular risk• Participants with higher peripheral vascular reactivity indices had a higher amplitude change from maximum to minimum and also showed enhanced reaction times to flicker provocation, which correlated to the degree of peripheral vascular function. 2. The effects of physical training on retinal and systemic microvascular function• Physical exercise positively influenced the retinal microcirculation through improvements in dilation and constriction reaction times to flicker provocation. 3. The long-lasting effects of fasting during the month of Ramadan on retinal and peripheral vascular function• Participants during fasting had a higher capacity to reach maximum dilation and also a greater percentage increase from baseline diameters. The retinal veins were also significantly less variable during baseline corrected measurements. 4. The effect of bariatric surgery on retinal vessels structure and systemic microvascular function• Increases were recorded for the diameter of retinal arteries but also for the veins. Peripheral vascular function was significantly improved and arterial stiffness was decreased. CVD risk was significantly decreased and also correlated with retinal vessel calibre measurements. 5. Is there an improvement in anterior ocular health after bariatric surgery?• Anterior surface health doesn’t necessarily cause ocular health problems in obese individuals nor can it be improved or ameliorated through bariatric surger

Life Sciences Program Tasks and Bibliography for FY 1997

This document includes information on all peer reviewed projects funded by the Office of Life and Microgravity Sciences and Applications, Life Sciences Division during fiscal year 1997. This document will be published annually and made available to scientists in the space life sciences field both as a hard copy and as an interactive internet web page

Novel Aspects of Lipoprotein Metabolism with Focus on Systemic Inflammation

With cardiometabolic diseases still topping the list of mortality causes and in facing the obesity and diabetes epidemic, there remains a great need to better understand the pathophysiological derangements underlying these conditions. During the past years, it has become increasingly appreciated that low grade systemic inflammation is a common hallmark of cardiometabolic disorders—not only concerning diabetes and atherosclerotic cardiovascular disease but also involving non-alcoholic fatty liver disease. Recently developed high-throughput laboratory techniques for lipidomics and metabolomics have enabled researchers to discern novel crosstalk pathways between lipid phenotypes and enhanced chronic inflammation. With this Special Issue of the Journal of Clinical Medicine, entitled “Novel Aspects of Lipoprotein Metabolism with a Focus on Systemic Inflammation”, researchers were invited to submit original papers and reviews on various topics, in particular, at the interface of lipid metabolism and inflammation

Report of the Surgeon General

In 1964, the first Surgeon General's report on the effects of smoking on health was released. In the nearly 50 years since, extensive data from thousands of studies have consistently substantiated the devastating effects of smoking on the lives of millions of Americans. Yet today in the United States, tobacco use remains the single largest preventable cause of death and disease for both men and women. Now, this 2010 report of the Surgeon General explains beyond a shadow of a doubt how tobacco smoke causes disease, validates earlier findings, and expands and strengthens the science base. Armed with this irrefutable data, the time has come to mount a full-scale assault on the tobacco epidemic. More than 1,000 people are killed every day by cigarettes, and one-half of all long-term smokers are killed by smoking-related diseases. A large proportion of these deaths are from early heart attacks, chronic lung diseases, and cancers. For every person who dies from tobacco use, another 20 Americans continue to suffer with at least one serious tobacco-related illness. But the harmful effects of smoking do not end with the smoker. Every year, thousands of nonsmokers die from heart disease and lung cancer, and hundreds of thousands of children suffer from respiratory infections because of exposure to secondhand smoke. There is no risk-free level of exposure to tobacco smoke, and there is no safe tobacco product. This new Surgeon General's report describes in detail the ways tobacco smoke damages every organ in the body and causes disease and death. We must build on our successes and more effectively educate people about the health risks of tobacco use, prevent youth from ever using tobacco products, expand access to proven cessation treatments and services, and reduce exposure to secondhand smoke. Putting laws and other restrictions in place, including making tobacco products progressively less affordable, will ultimately lead to our goal of a healthier America by reducing the devastating effects of smoking. This 2010 Surgeon General's report represents another important step in the developing recognition, both in this nation and around the world, that tobacco use is devastating to public health. Past investments in research and in comprehensive tobacco control programs--combined with the findings presented by this new report--provide the foundation, evidence, and impetus to increase the urgency of our actions to end the epidemic of tobacco use.CDC-INFO Pub ID 220456220456U.S. Department of Health and Human Services. How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2010.Chapter 1. Introduction, evaluation of evidence on mechanisms of disease production, and summary -- Chapter 2. The changing cigarette -- Chapter 3. Chemistry and toxicology of cigarette smoke and biomarkers of exposure and harm -- Chapter 4. Nicotine addiction: past and present -- Chapter 5. Cancer -- Chapter 6. Cardiovascular diseases -- Chapter 7. Pulmonary diseases -- Chapter 8. Reproductive and developmental effects -- Chapter 9. A vision for the future -- List of abbreviations -- List of tables and figures -- Definitions and alternative nomenclature of genetic symbols used in this report -- Index.2010704

Vitamin C in Health and Disease

Vitamin C is a pivotal water soluble electron donor in nature and an essential nutrient in man. Despite its many years as a research focus, new and increasingly regulatory functions of vitamin C in human health are continually being unravelled. This improved mechanistic insight is starting to provide rationales explaining the extensive epidemiological literature that, for decades, has consistently shown strong associations between poor vitamin C status and increased morbidity and mortality. In this Special Issue, we include original research and literature reviews by experts in the field outlining the roles of vitamin C in early, daily and late life, as well as the roles of deficiency in cardiovascular disease, inflammation and cancer

Intracoronary ultrasound

Knowledge of the characteristics of the atherosclerotic plaque (eccentricity, composition, effect of initial dilatation or ablation) and of the flow modifications induced by a coronary stenosis would establish more precisely the severity of the lesion under evaluation, improve the planning and guidance of therapeutic interventions, and facilitate the detection of subsequent complications. The miniaturization of the ultrasound catheters a11d the de