The first contribution presents coumarins, the largest group of 1-benzopyran derivatives found in plants. Coumarin chemistry remains one of the major interest areas of phytochemists, especially because of their structural diversity and medicinal properties, along with the wide-ranging bioactivities of these compounds, inclusive of analgesic, anticoagulant anti-HIV, anti-inflammatory, antimicrobial, antineoplastic, antioxidant, and immunomodulatory effects. The second contribution presents a comprehensive survey of the many aspects of PAD biochemistry and physiology. The third contribution gives a comprehensive overview of secondary metabolites from higher fungi, with more than 700 references highlighting the isolation, structure elucidation, biological activities, chemical synthesis, and biosynthesis of pigments, nitrogen-containing compounds, and terpenoids from mushrooms.

The series Topics in Heterocyclic Chemistry presents critical reviews on present and future trends in the research of heterocyclic compounds. Overall the scope is to cover topics dealing with all areas within heterocyclic chemistry, both experimental and theoretical, of interest to the general heterocyclic chemistry community. The series consists of topic related volumes edited by renowned editors with contributions of experts in the field. All chapters from Topics in Heterocyclic Chemistry are published Online First with an individual DOI. In references, Topics in Heterocyclic Chemistry is abbreviated as Top Heterocycl Chem and cited as a journal.

This thesis focuses on the development of gold- and non-classical platinum-based anti-cancer agents that display distinctively different anti-cancer mechanisms compared to the commonly used cisplatin. These metal complexes contain N-heterocyclic carbene (NHC) ligands which are able to form strong M-C(NHC) bonds, conferring high stability and favorable lipophilicity, reactivity and binding specificity of metal complexes on biomolecules. The author demonstrates significant advances made in anti-cancer gold(III), gold(I) and platinum(II) complexes. Detailed chemical synthesis, in vitro and/or in vivo anti-cancer activities are clearly presented including: (i) a class of Au(III) complexes containing a highly fluorescent N^N^N ligand and NHC ligand that simultaneously act as fluorescent thiol "switch-on" probes and anti-cancer agents; (ii) a dinuclear gold(I) complex with a mixed diphosphine and bis(NHC) ligand displaying favorable stability and showing significant inhibition of tumor growth in two independent mice models with no observable side effects; and (iii) a panel of stable luminescent cyclometalated platinum(II) complexes exhibiting high specificity to localize to the endoplasmic reticulum (ER) domain, inducing ER stress and cell apoptosis. These works highlight the clinical potential that gold and platinum complexes offer for cancer treatment.

This book is written for researchers, undergraduate students and postgraduate students, physicians and traditional medicine practitioners who develop research in the field of neurosciences, phytochemistry and ethnopharmacology or can be useful for their practice. Topics discussed include the description of depression, its biochemical causes, the targets of antidepressant drugs, animal and cell models commonly used in the research of this pathology, medicinal plants and bioactive compounds with antidepressant activity used in traditional medicine, advances in nanotechnology for drug delivery to the brain and finally the future challenges for researchers studying this pathology.

The Computational Biomechanics for Medicine titles provide an opportunity for specialists in computational biomechanics to present their latest methodologies and advancements. This volume comprises eighteen of the newest approaches and applications of computational biomechanics, from researchers in Australia, New Zealand, USA, UK, Switzerland, Scotland, France and Russia. Some of the interesting topics discussed are: tailored computational models; traumatic brain injury; soft-tissue mechanics; medical image analysis; and clinically-relevant simulations. One of the greatest challenges facing the computational engineering community is to extend the success of computational mechanics to fields outside traditional engineering, in particular to biology, the biomedical sciences, and medicine. We hope the research presented within this book series will contribute to overcoming this grand challenge.

This book begins with the basic terms and definitions and takes a student, step by step, through all areas of medical physics. The book covers radiation therapy, diagnostic radiology, dosimetry, radiation shielding, and nuclear medicine, all at a level suitable for undergraduates. This title not only describes the basics concepts of the field, but also emphasizes numerical and mathematical problems and examples. Students will find An Introduction to Medical Physics to be an indispensible resource in preparations for further graduate studies in the field.

This book offers an overview of our current understanding of host defense peptides and their potential for clinical applications as well as some of the obstacles to this. The chapters, written by leading experts in the field, detail the number and diversity of host defense peptides, and discuss the therapeutic potential not only of antibacterial, but also of antifungal, antiviral, plant antimicrobial and anticancer host defense peptides. The authors provide new insights into their mechanisms of action and their immunomodulatory properties, and review recent advances in the design of novel therapeutic molecules. Lastly, their potential to prevent preterm births and Staphylococcus aureus infections is highlighted. The book is of interest to researchers, industry and clinicians alike.

Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

Authored by world renowned scientists, this book expertly reviews all the imaging techniques and exciting new methods for the analysis of the pain, including novel tracers, biomarker, metabolomic and gene-array profiling, together with cellular, genetic, and molecular approaches. Recent advances in human brain imaging techniques have allowed a better understand of the functional connectivity in pain pathways, as well as the functional and anatomical alterations that occur in chronic pain patients. Modern imaging techniques have permitted rapid progress in the understanding of networks in the brain related to pain processing and those related to different types of pain modulation. Neuroimaging of Pain is designed to be a valuable resource for radiologists, neuroradiologists, neurologists and neuroscientists, working in hospitals and universities from junior trainees to consultants.

This thesis reports the latest developments in the direct amination of various C H bonds using an H Zn exchange/electrophilic amination strategy. McDonald and co-workers reveal this approach to be a rapid and powerful method for accessing a variety of functionalized amines. The material outlined in this book shows how McDonald achieved C H zincation using strong, non-nucleophilic zinc bases and subsequent electrophilic amination of the corresponding zinc carbanions with copper as a catalyst and O-benzoylhydroxylamines as the electrophilic nitrogen source. McDonald's findings are of relevance to medicinal chemistry, drug discovery and materials science. Her thesis is a source of inspiration for scientists entering the field and students beginning their PhD in a related area.

This book surveys recent advances in theranostics based on magnetic nanoparticles, ultrasound contrast agents, silica nanoparticles and polymeric micelles. It presents magnetic nanoparticles, which offer a robust tool for contrast enhanced MRI imaging, magnetic targeting, controlled drug delivery, molecular imaging guided gene therapy, magnetic hyperthermia, and controlling cell fate. Multifunctional ultrasound contrast agents have great potential in ultrasound molecular imaging, multimodal imaging, drug/gene delivery, and integrated diagnostics and therapeutics. Due to their diversity and multifunctionality, polymeric micelles and silica-based nanocomposites are highly capable of enhancing the efficacy of multimodal imaging and synergistic cancer therapy. This comprehensive book summarizes the main advances in multifunctional nanoprobes for targeted imaging and therapy of gastric cancer, and explores the clinical translational prospects and challenges. Although more research is needed to overcome the substantial obstacles that impede the development and availability of nanotheranostic products, such nontrivial nanoagents are expected to revolutionize medical treatments and help to realize the potential of personalized medicine to diagnose, treat, and follow-up patients with cancer. Zhifei Dai is a Professor at the Department of Biomedical Engineering, College of Engineering, Peking University, China.

Artificial organs may be considered as small-scale process plants, in which heat, mass and momentum transfer operations and, possibly, chemical transformations are carried out. This book proposes a novel analysis of artificial organs based on the typical bottom-up approach used in process engineering. Starting from a description of the fundamental physico-chemical phenomena involved in the process, the whole system is rebuilt as an interconnected ensemble of elemental unit operations. Each artificial organ is presented with a short introduction provided by expert clinicians. Devices commonly used in clinical practice are reviewed and their performance is assessed and compared by using a mathematical model based approach. Whilst mathematical modelling is a fundamental tool for quantitative descriptions of clinical devices, models are kept simple to remain focused on the essential features of each process. Postgraduate students and researchers in the field of chemical and biomedical engineering will find that this book provides a novel and useful tool for the analysis of existing devices and, possibly, the design of new ones. This approach will also be useful for medical researchers who want to get a deeper insight into the basic working principles of artificial organs.

This thesis describes the inception, design, and implementation of stereoselective desymmetrization reactions in the total synthesis of the natural products pactamycin and paspaline. In the case of pactamycin, the author develops a novel asymmetric Mannich reaction and symmetry-breaking reduction strategy to enable facile construction of the complex core architecture in fifteen steps using commercially available materials - the shortest synthesis to date. He subsequently demonstrates the flexibility of this approach in SAR investigations by highlighting the preparation of twenty-five unique pactamycin structural congeners. For paspaline, the author develops a biocatalytic desymmetrization strategy that allows the highly controlled synthesis of core stereochemistry and provides a platform for the development of new conceptual disconnections in the synthesis of "steroid-like" natural products. This thesis offers a valuable resource for students embarking on a PhD in total synthesis.

This thesis reports studies on the substrate specificity of crucial ketosynthase (KS) domains from trans-AT Polyketide Synthases (PKSs). Using a combination of electrospray ionisation-mass spectrometry (ESI-MS) and simple N-acetyl cysteamine (SNAC) substrate mimics, the specificity of a range of KS domains from the bacillaene and psymberin PKSs have been succsessfully studied with regard to the initial acylation step of KS-catalysis. In addition, the ability to alter the substrate tolerance of KS domains by simple point mutations in the active site has been demonstrated. A series of acyl-ACPs have been synthesised using a novel methodology and employed to probe the substrate specificity of both KS domains and the previously uncharcterised acyl hydrolase domain, PedC. KS-catalysed chain elongation reactions have also been conducted and monitored by ESI-MS/MS. All KS domains studied exhibited higher substrate specificity at the elongation step than in the preceeding acylation step. Furthermore, a mechanism of reversible acylation is proposed using the PsyA ACP1-KS1 di-domain. The findings in this thesis provide important insights into mechanisms of KS specificity and show that mutagenesis can be used to expand the repertoire of acceptable substrates for future PKS engineering.

This book reviews the fundamental aspects of quinoxaline chemistry: synthesis, reactions, mechanisms, structure, properties, and uses. The first four chapters present a survey of the developments in quinoxaline chemistry since the publication of the monograph on "Condensed Pyrazines" by Cheeseman and Cookson in 1979. These chapters give comprehensive coverage of all the methods of the synthesis of quinoxalines and the important quinoxaline-containing ring systems such as thiazolo[3,4-a]-, pyrrolo[1,2-a]-, and imidazo[1,5-a]quinoxalines. Chapter five describes many new methods for the construction of quinoxaline macrocycles, which are important in applications such as optical devices and materials. The final chapter reviews all previously known rearrangements of heterocyclic systems that lead to benzimidazole derivatives. Mamedov critically analyses these transformations to reveal a novel acid-catalyzed rearrangement of quinoxalinones giving 2-heteroarylbenzimidazoles and 1-heteroarylbenzimidazolones in the presence of nucleophilic reactants (MAMEDOV Heterocycle Rearrangement). This book is of interest to researchers in the fields of heterocyclic and synthetic organic chemistry.

The series Topics in Heterocyclic Chemistry presents critical reviews on present and future trends in the research of heterocyclic compounds. Overall the scope is to cover topics dealing with all areas within heterocyclic chemistry, both experimental and theoretical, of interest to the general heterocyclic chemistry community. The series consists of topic related volumes edited by renowned editors with contributions of experts in the field. All chapters from Topics in Heterocyclic Chemistry are published Online First with an individual DOI. In references, Topics in Heterocyclic Chemistry is abbreviated as Top Heterocycl Chem and cited as a journal.

This volume of Modern Aspects of Electrochemistry reviews the latest developments in electrochemical science and technology related to biomedical and pharmaceutical applications. In particular, this book discusses electrochemical applications to medical devices, implants, antimicrobially active materials, and drug delivery systems.

This book moves away from the frameworks that have traditionally guided ethical decision-making in the Western clinical setting, towards an inclusive, non-coercive and, reflective dialogic approach to moral decision-making. Inspired in part by Jurgen Habermas's discourse theory of morality and principles of communicative action, the book offers a proportionist approach as a way of balancing out the wisdom in traditional frameworks, set in the actual reality of the clinical situation at hand. Putting this approach into practice requires having a conversation, a dialogue or a discourse, with collaboration amongst all the stakeholders. The aim of the dialogue is to reach consensus in the decision, via mutual understanding of the values held by the patient and others whom they see as significant. This book aims to underscore the moral philosophical foundations for having a meaningful conversation. Life and Death Decision in the Clinical Setting is especially relevant in our contemporary era, characterised medically by an ever-increasing armamentarium of life-sustaining technology, but also by increasing multiculturalism, a multiplicity of faiths, and increasing value pluralism.

"Organic Trace Analysis" presents the basics of trace analysis, from sample preparation to the measurement: Students are introduced to statistical evaluation, quality control technologies, sampling and preparation of organic traces, as well as to enrichment and separation of samples. Spectroscopic techniques as chromatography, capillary electrophoresis, mass spectrometry, and receptor-based bioanalysis are presented in detail.

Blood science has become a cornerstone of multiple disciplines, including clinical chemistry, disease diagnosis, and therapeutic monitoring. Over the past decade, we have witnessed the advent of increasingly powerful proteomics technologies that allow greater fundamental insights into the blood proteome. These technological improvements have, in part, fuelled the quest for the discovery of novel blood-based biomarkers of disease. Serum/Plasma Proteomics: Methods and Protocols is a comprehensive resource of protocols for areas, pre-analytical through to analytical, of plasma and serum proteomics. Divided into five convenient sections, this detailed volume covers fractionation strategies for in-depth blood proteome analysis, defined procedures for blood collection, handling and storage, detailed protocols for performing both antibody-based and non-antibody based quantitative assays, proteome analysis of blood cell compartments, circulating nanomebraneous vesicles and blood-related fluids, and finally data management, statistical design, and bioinformatic challenges. This book, contributed to by leading experts in the field, provides a valuable foundation for the development and application of blood-based proteomics. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Serum/Plasma Proteomics: Methods and Protocols, with its well-honed methodologies, seeks to serve both professionals and investigators new to the field in an effort to further our knowledge of this fundamental science.

The Springer Handbook of Enzymes provides concise data on some 5,000 enzymes sufficiently well characterized - and here is the second, updated edition. Their application in analytical, synthetic and biotechnology processes as well as in food industry, and for medicinal treatments is added. Data sheets are arranged in their EC-Number sequence. The new edition reflects considerable progress in enzymology: the total material has more than doubled, and the complete 2nd edition consists of 39 volumes plus Synonym Index. Starting in 2009, all newly classified enzymes are treated in Supplement Volumes.

The Springer Handbook of Enzymes provides concise data on 4,457 enzymes - and here is the second, updated edition. The enzymes are sufficiently well characterized for application in analytical, synthetic and biotechnology processes as well as in food industry. Data sheets are arranged in their EC-Number sequence. The new edition reflects considerable progress in enzymology: the total material has more than doubled, and the complete 2nd edition consists of 39 volumes plus synonym index.

The future of oncology seems to lie in Molecular Medicine (MM). MM is a new science based on three pillars. Two of them are evident in its very name and are well known: medical science and molecular biology. However, there is a general unawareness that MM is firmly based on a third, and equally important, pillar: Systems Biomedicine. Currently, this term denotes multilevel, hierarchical models integrating key factors at the molecular, cellular, tissue, through phenotype levels, analyzed to reveal the global behavior of the biological process under consideration. It becomes increasingly evident that the tools to construct such complex models include, not only bioinformatics and modern applied statistics, as is unanimously agreed, but also other interdisciplinary fields of science, notably, Mathematical Oncology, Systems Biology and Theoretical Biophysics.

Membrane Receptors, Channels and Transporters in Pulmonary Circulation is a proceeding of the 2008 Grover Conference (Lost Valley Ranch and Conference Center, Sedalia, Colorado; September 3-7, 2008), which provided a forum for experts in the fields of those receptors, channels and transporters that have been identified as playing key roles in the physiology and pathophysiology of the pulmonary circulation. The book rigorously addresses: i) recent advances in our knowledge of receptors, channels and transporters and their role in regulation of pulmonary vascular function; ii) how modulation of expression and function of receptors, channels and transporters and their interrelationships contribute to the pathogenesis of pulmonary vascular disease; and iii) the therapeutic opportunities that may be revealed by enhancing our understanding of this area. The overall goal was to explore the mechanisms by which specific receptors, channels and transporters contribute to pulmonary vascular function in both health and disease, and how this knowledge may lead to novel interventions in lung dysplasia, pulmonary edema, lung injury, and pulmonary and systemic hypertension to reduce and prevent death from lung disease. Membrane Receptors, Channels and Transporters in Pulmonary Circulation is divided into six parts. Part 1 (Ion Channels in the Pulmonary Vasculature: Basics and New Findings) is designated for basic knowledge and recent findings in the research field of ion channels in pulmonary circulation. There are five chapters in Part I discussing the function, expression, distribution and regulation of various ion channels present in pulmonary vascular smooth muscle cells and how these channels are integrated to regulate intracellular Ca2+ and cell functions. Part II (TRP Channels in the Pulmonary Vasculature: Basics and New Findings) is composed of five chapters that are exclusively designed to discuss the role of a recently identified family of cation channels, transient receptor potential (TRP) channels, in the regulation of pulmonary vascular tone and arterial structure. Part III (Pathogenic Role of Ion Channels in Pulmonary Vascular Disease) includes four chapters that discuss how abnormal function and expression of various ion channels contribute to changes in cell functions and the development of pulmonary hypertension. Part IV (Receptors and Signaling Cascades in Pulmonary Arterial Hypertension) consists of five chapters devoted to the role of bone morphogenetic protein receptors, Notch receptors, serotonin receptors, Rho kinase and vascular endothelial growth factor receptors in the development of pulmonary arterial hypertension. Part V (Receptors and Transporters: Role in Cell Function and Hypoxic Pulmonary Vasoconstriction) includes four chapters designed to illustrate the potential mechanisms involved in oxygen sensing and hypoxia-induced pulmonary vasoconstriction and hypertension. Part VI (Targeting Ion Channels and Membrane Receptors in Developing Novel Therapeutic Approaches for Pulmonary Vascular Disease) consists five chapters which discuss the translational research involving on membrane receptors, channels and transporters, including their potential as novel drug targets. We hope that Membrane Receptors, Channels and Transporters in Pulmonary Circulation will allow readers to foster new concepts and new collaborations and cooperations among investigators so as to further understand the role of receptors, channels and transporters in lung pathophysiology. The ultimate goal is to identify new mechanisms of disease, as well as new therapeutic targets for pulmonary vascular diseases. An additional outcome should be enhanced understanding of the role of these entities in systemic vascular pathophysiology, since the conference will include researchers and clinicians with interests in both pulmonary and systemic circulations.

This book, with its 16 chapters, documents the present state of knowledge of the adenosine A receptor. It covers a wide range of information, including data from 3 studies of theoretical, molecular and cellular pharmacology, signal transduction, integrative physiology, new drug discoveries and clinical applications. It fills an important gap in the literature since no alternative source of such information is currently available. Although the A receptor is increasingly being recognized for 3 its increasing number of biological roles throughout the body and many A receptor 3 ligands have proven useful in elucidating peripheral and central pathologies, many issues remain unresolved. Moreover, research activity in this field continues to grow exponentially, resulting in a constant flow of new information. The chapters in this book cover both basic science and the relevant applications and provide an authoritative account of the current status of the field. They have enabled my goal as editor to make "A Adenosine Receptors from Cell Biology to Pharmacology and 3 Therapeutics" an up to date, scientifically excellent, reference source, attractive to basic and clinical scientists alike, a reality. Detailed understanding of the physico-chemical aspects and molecular biology of the A receptor provides a solid basis for its future development as a target for 3 adenosine-based pharmacotherapies (Chapters 2 and 3).