Resolution Pharmacology Innovative Therapeutic Approaches Based On The Biology Of Resolution To Control Chronic Diseases Of Western Societies

In this eBook, we have grouped together 16 original contributions which have addressed the translational potential for therapeutics developed on the conceptual framework of the resolution of inflammation. The take home message of our effort, and the efforts of our colleagues who wrote these pieces, is that completely different drugs can be designed and modelled on the mediators and targets of resolution. By implementing this 180° shift in the way we plan the drug development programme (that is by focusing on agonists and/or promoting the actions of pro-resolution agonists) we can offer a fresh approach to the clinical management of chronic diseases that affect the modern society. With this series of articles we foresee the birth of Resolution Pharmacology. The 16 contributions presented herein confirm the broad relevance of pro-resolving physio-pharmacology with the description of pro-resolving mechanisms in distinct diseases, from atherosclerosis and heart infarct, to cystic fibrosis and diabetes. This testifies on one hand the fundamental role that inflammatory mechanisms play in virtually all pathological settings and, on the other hand, the great potential that a novel approach to anti-inflammatory therapy by exploiting resolution mediators and targets may have. Thus, while there is broad recognition that evidence-based interventions have transformed cardiovascular, inflammation and endocrine care, new therapies are still needed for growing numbers of patients with unmet needs. As an example, an estimated 17 million people world-wide die annually of cardiovascular diseases, particularly heart attacks and strokes. Cardiovascular diseases occur almost equally in men and women and are the leading cause of death and morbidity worldwide. It is estimated that only 1/1,000 compounds entering preclinical testing are then trialled in man and the actual cost of developing a new therapeutic into clinical practice has grown exponentially over the past two decades (estimated $1.2B). Over the last 20 years or more, scientists have appreciated the biology of the resolution of inflammation, which provides a new paradigm in our understanding of the inflammatory process with the appreciation of genetic, molecular and cellular mechanisms that are engaged to actively resolve inflammation. The ‘resolution of acute inflammation’ is enabled by counter-regulatory checkpoints to terminate the host reaction while at the same time promoting healing and repair. The potential of lipid mediators to enact pro-resolving effects in the context of cystic fibrosis is presented by Recchiuti et al., while Fredman reasons on the potential for these molecules in atherosclerosis. This resonates well with the contributions from Bäck and colleagues who have focused on pro-resolving receptors to offer vasculo-protection in intimal hyperplasia and more generally in cardiovascular disease. On the same vein is the scholar contribution of Leoni and Soehnlein who focus on heart disease, with Qin et al. presenting the latest findings on the effect of an Annexin A1-derived peptide in myocardial infarction. Hansen et al. and de Gaetano et al. bring in the complexity of diabetes and associated morbidity with a focus on specialised pro-resolving lipid mediators but also introducing the potential of dietary approaches. As the western diet favours disease, an omega-3 rich diet can lead to higher availability of lipid mediators to afford tissue protection if not reverting its pathological status. Docosahexaenoic acid and its bioactive derivatives are endowed with potent anti-nociceptive properties following bone fracture, as shown by Zhang et al. The broad relevance of the pharmacological approach reaches the skin with Resolvin D1 protecting against UV irradiation (Saito et al.). Reduced skin inflammation is also achieved with an Annexin A1 peptide that impacts on the outcome of heterologous transplantation (Lacerda et al.). Indeed, modulating the phenotype of immune cells can provide long lasting beneficial outcomes, as attained with CDK inhibitors (Cartwright et al.) and PI3K inhibitors in experimental gout (Galvao et al.). Such an effect is also achieved with a third group of pro-resolving therapeutics, the melanocortin receptor agonists, with important modulation of macrophage reactivity (Patruno et al.) with Spana et al., providing new pharmacology following selective activation of the MC1 receptor. Finally, Hopkin et al. discuss the potential for targeting immune cell trafficking as a way to control immune mediated diseases, bringing in not only pro-resolving mediator agonists, but also approaches to reduce chemo/cytokine gradients or modulating S1P and 11-beta hydroxysteroid dehydrogenase. Finally, we wish to highlight that this wealth of science has also bought to the forefront specific pro-resolving receptors (including FPR2/ALX, GPR32, ChemR23 and MC1), all G protein coupled receptors that are therefore amenable to pharmacological exploitation for drug discovery programmes. We see that not only agonists to the receptors can be developed, some of them modelled on the natural ligands (e.g. resolvins, lipoxins, Annexin A1-derived peptides or melanocortin peptides), but also that the creativity of this pharmacology can be attained through biased ligands and positive allosteric modulators. Deep knowledge of pro-resolving receptor biology and their cell-specific signalling can accelerate the generation of novel anti-inflammatory depicted on the resolution of inflammation. In conclusion, with this eBook, we propose time is ready to exploit the concepts of resolution and use its targets and mediators for the identification of better drugs to establish ‘Resolution Pharmacology’. We predict Resolution Pharmacology will represent an important innovation in the way common diseases will be treated in the next decades of this millennium.

Drug overdose, driven largely by overdose related to the use of opioids, is now the leading cause of unintentional injury death in the United States. The ongoing opioid crisis lies at the intersection of two public health challenges: reducing the burden of suffering from pain and containing the rising toll of the harms that can arise from the use of opioid medications. Chronic pain and opioid use disorder both represent complex human conditions affecting millions of Americans and causing untold disability and loss of function. In the context of the growing opioid problem, the U.S. Food and Drug Administration (FDA) launched an Opioids Action Plan in early 2016. As part of this plan, the FDA asked the National Academies of Sciences, Engineering, and Medicine to convene a committee to update the state of the science on pain research, care, and education and to identify actions the FDA and others can take to respond to the opioid epidemic, with a particular focus on informing FDA's development of a formal method for incorporating individual and societal considerations into its risk-benefit framework for opioid approval and monitoring.

The Institute of Medicine study Crossing the Quality Chasm (2001) recommended that an interdisciplinary summit be held to further reform of health professions education in order to enhance quality and patient safety. Health Professions Education: A Bridge to Quality is the follow up to that summit, held in June 2002, where 150 participants across disciplines and occupations developed ideas about how to integrate a core set of competencies into health professions education. These core competencies include patient-centered care, interdisciplinary teams, evidence-based practice, quality improvement, and informatics. This book recommends a mix of approaches to health education improvement, including those related to oversight processes, the training environment, research, public reporting, and leadership. Educators, administrators, and health professionals can use this book to help achieve an approach to education that better prepares clinicians to meet both the needs of patients and the requirements of a changing health care system.

The New Public Health has established itself as a solid textbook throughout the world. Translated into 7 languages, this work distinguishes itself from other public health textbooks, which are either highly locally oriented or, if international, lack the specificity of local issues relevant to students' understanding of applied public health in their own setting. This 3e provides a unified approach to public health appropriate for all masters' level students and practitioners—specifically for courses in MPH programs, community health and preventive medicine programs, community health education programs, and community health nursing programs, as well as programs for other medical professionals such as pharmacy, physiotherapy, and other public health courses. Changes in infectious and chronic disease epidemiology including vaccines, health promotion, human resources for health and health technology Lessons from H1N1, pandemic threats, disease eradication, nutritional health Trends of health systems and reforms and consequences of current economic crisis for health Public health law, ethics, scientific d health technology advances and assessment Global Health environment, Millennium Development Goals and international NGOs

This book offers a comprehensive study of C-reactive protein (CRP) belonging to the pentraxin family, including a brief history of CRP, its structure, synthesis and evolution. Focusing on the emerging role of CRP and its clinical application in the field of disease biology, it details the pathophysiological role of CRP in a host of diseases such as cardiovascular disease, diabetes, cancers, rheumatoid arthritis and infectious diseases and others. It also discusses the role of innate immunity and acute phase response (APR) and their key mediators in the host body in response to tissue injury, infection, trauma or surgery, immunological disorders or neoplastic growth. CRP’s significance in inflammation is highlighted, and its importance as a clinical marker in cardiovascular disease, its functional significance in Leishmania and Plasmodium infections, its association with the development of insulin resistance in type 2 diabetes mellitus, and its role in cancer are discussed in detail. The book also includes clinical data studies and presents the latest research advances to further readers’ understanding of CRP.

"This is a very good text for undergraduate students as it gives a broad overview of the concept of public health, utilising case studies to illustrate practical application. This book would be also be an excellent way for practitioners to increase their own knowledge of public health and could inform their own continuing professional development." Julie Lemprière, University of Gloucestershire Key Concepts in Public Health identifies fifty key concepts used across the discipline of public health in order to give the reader a broad perspective of the core topics relevant to training and practice. From epidemiology to health promotion, and ethics to leadership, the book offers an exciting guide to the multiprofessional field. Each entry features: - a snapshot definition of the concept - a broader discussion addressing the main issues and links to practice - key points relevant to the entry - case studies to illustrate the application to practice - examples of further reading. Highly readable, with clear indexing and cross referencing, this is an ideal book to turn to for learning more about key issues in public health practice and education. The clever structure means the book can be read in its entirety to support a programme of study or readers can use it to dip into and update their knowledge of a particular concept. It meets the validation requirements of all allied health and nursing training programmes and will also be invaluable for policy-makers and healthcare practitioners continuing their professional education.

Continuous Renal Replacement Therapy (CRRT) is the standard of care for management of critically ill patients with acute renal failure. Part of the Pittsburgh Critical Care series, Continuous Renal Replacement Therapy provides concise, evidence-based, bedside guidance about this treatment modality, offering quick reference answers to clinicians' questions about treatments and situations encountered in daily practice. Organized into sections on theory, practice, special situations, and organizational issues, this volume provides a complete view of CRRT theory and practice. Tables summarize and highlight key points, and key studies and trials are included in each chapter. The second edition has been updated to include a new chapter on the use of biomarkers to aid in patient selection and timing, extensive revisions on terminology and nomenclature to match current standards, and the most up-to-date information on newly developed CRRT machines.