Host defense to intracellular pathogens depends upon both innate and adaptive cell-mediated immune responses. Polymorphonuclear neutrophil leukocytes which belong to the innate immune system are the first cells that are recruited massively within hours of microbial infection. The importance of neutrophils in the development of an immune response is only emerging as they have long been considered by immunologists as short lived, non-dividing cells, of poor interest. Now, neutrophils are emerging as key components of the inflammatory response, and are shown to have immunoregulatory roles in microbial infections. The impact of neutrophils on cells present at the site of infection is only beginning to be studied and deserves more attention. This e-book provides an overview of the recent advances made in the field of neutrophil biology and motions towards some of the exciting new directions in which neutrophil research is moving.

This comprehensive ebook covers all the aspects of ADME/PK modeling including solubility, absorption, formulation, metabolic stability, drug-drug interaction potential and a special delivery tool of drug candidates. The book provides an integrated view of fundamental ADME issues and challenges in early drug development from the aspect of practicing drug researchers. It also provides valuable help for the medicinal chemist in the process of multiple optimization.

Human Immunodeficiency Virus (HIV) infection represents one of the biggest challenges of current years. However, scientists and physicians still do not have an efficient therapy for preventing or eradicating the virus. The selection of drug-resistant strains as well as side-effects, represent common problems encountered in all anti-viral therapies. However, it has been clearly demonstrated that the potency of early immune responses profoundly regulates levels of HIV, and hence also the generation of virus mutants as well as the velocity of disease progression to AIDS. A prominent feature of this e-book is the focus on interaction between innate immunity and HIV infection. This topic has been investigated by many authors from the late 80's, and many soluble factors responsible for such activity have been discovered, such as suPAR and HMGB1. At present, these two novel factors are the subject of very intense research on HIV infections. A key advantage of this e-book is the selection of authors, recognized worldwide as leading experts in their field. Because of the comprehensive coverage, as well as the eminence of the authors, this e-book provides a detailed and high quality description about the role of innate immune responses regulating HIV replication. It should prove to be a useful resource for readers interested in immunology and HIV research.

Thermodynamics and kinetics (i.e., chemical interactions) are extremely important concepts for pharmaceutical scientists to understand since the “drug selection process”, that is, the process used by pharmaceutical companies to discover and develop marketable drugs, is totally dependent upon these theories. While both theories are important, kinetic models describing complex chemical and biological processes provide a unifying theory for all phases of the discovery and development of drugs. Unfortunately, in most textbooks the mathematical descriptions necessary to develop a deeper understanding of kinetic models are omitted. This is primarily done such that the underlying chemistry and biochemistry principles are not obscured by the “mathematical maze” that is generated from these models. As a result many chemists and biologists veer rapidly away from thermodynamics and kinetics. For some scientists, this can lead to confusion on how to apply these models to real-life situations. For example, many enzyme kinetic models are formulated as rate equations. Since experimentally measurements typically determine concentrations and rarely determines rates directly, confusion arises on how to apply kinetic models. In this case, either the model is integrated to give a description of the concentration course of the enzyme reaction or the data is differentiated (i.e., the process of determining rates) by measuring tangents to the reaction curves at zero time. The level of mathematical skills required to solve kinetic models is minimal for anyone who has studied college level algebra and calculus. Thus, the objective of this book is to present a brief review of thermodynamics and kinetics followed by a detailed step-by-step approach in developing and solving kinetic models for complex chemical and biological processes. The book focuses on building a solid mathematical foundation of enzyme kinetic models by systematically evolving simple uni- and bi-molecular models to enzyme models. Applications for some of these kinetic models are generated from pharmaceutical examples and a selection of problems is presented at the end of each chapter. This elementary approach has been intentionally selected to keep the book at a self-explanatory level. It is anticipated that the reader will be able to follow the mathematical operations and in the process develop a deeper understanding of kinetic models and an improved ability to interpret kinetic parameters. The book is restricted to solution chemical kinetics and does not deal with the theories of chemical reactions, gas-phase reactions, experimental kinetic methods and so on. There are many excellent chemical kinetic textbooks available for those interested in these topics. The solution chemical kinetics materials for the book were obtained from literature papers and several books on physical chemistry and enzyme kinetics. The ideas from these sources have been hopefully reinterpreted in a style that is well matched to those pharmaceutical scientists that do not have a comprehensive knowledge of kinetic models and the mathematical skills to solve them. Chapter 1 presents a general overview to thermodynamic and kinetic principals and theory. In Section i, an overview to the scope of the book is presented. A brief review of mathematical fundamentals used in the book (Section ii) and kinetic and thermodynamic principals are present (Section iii and iv). A glossary of symbols and abbreviation used throughout the book is presented in Section v. Chapter 2 describes the basic theory of first-order kinetic models. These types of mathematical models are used for irreversible (Section I) and reversible (Section II) rearrangement reactions and some examples are presented to illustrate their applications to drug discovery. Chapter 3 describes second-order irreversible (Section III) and reversible (Section IV) dimerization reactions while Chapter 4 describes second-order irreversible (Section V) and reversible (Section VI) binding reactions. Chapter 5 describes partially and fully coupled reversible completive binding reactions (Section VII). Chapter 6 describes second-order kinetic models that are used to analyze consecutive irreversible (Section VIII) and reversible (Section IX) substrate suicide enzyme reactions. Chapter 7 describes kinetic models that are used to analyze consecutive irreversible (Section X) and reversible (Sections XI and XII) enzyme reactions. Chapter 8 describes kinetic models that are used to analyze consecutive reversible inhibition enzyme reactions (Section XIII - XVI). Chapter 9 describes kinetic models that are used to analyze substrate (Section XVII) and product inhibition (Section XVIII) enzyme reactions. The Appendix contains the answers to the problems.

Antibodies Applications and New Developments is an overview of the current developments of techniques and methods relating to immunodiagnostics and immunoanalysis. This eBook also deals with specialties in the fields of drug, pesticide, antigen and food contaminant detection. The volume is useful for professional immunologists and biotechnologists interested in antibody research and development.

The book is dedicated to the history and current status of physiologic autoimmunity concept and relation between autoimmunity and autoallergy in the context of disease prevention and prediction. The immune system is a natural component, regulator and direct participant in the physiological activities in a healthy body. The main forms of physiological activity of the immune system are based on the intrinsic abilities of self-identification, self-maintenance, self-regulation, and self-reparation — that is recognizing components of the “self ”, i.e. natural autoimmunity. The most ancient and homeostatically important functions of natural autoimmunity are autoclearance as well as construction and support of multicellularity. A considerable number of immune functions, including those related to antimicrobial defense, derive from these basic ones. Various pathological processes in any organ are usually accompanied by different patterns of cell death and, thus, by increased exposure and presentation of self antigens. These events induce the secondary rise in production of autoantibodies with appropriate specificity (opsonines), which provides augmentation of clearance by facilitating the efficacy of macrophage-dependent consumption of debris in the aff ected organ. This phenomenon is sanogenic in nature and adaptive in essence. Therefore, secondary changes in production and serum content of autoantibodies can be considered the universal and earliest detectable marker of any chronic disease. In relation to experimental production and clinical reveal of antibodies towards nuclear antigens, penetrating into living cell nuclei and altering nuclear acid synthesis, cell proliferation and function, autoantibodies can be regarded as hormone-like bioregulators of gene expression. Apparently, immune system is able to reproduce complementary regulators for various cell receptors, including nuclear ones. Book is unique, it is a single monograph comprehensively including history and current status of natural autoimmunity problem. It describes a fundamental concept essencial for every branch of Medicine and Pathology. The concept described has broad practical application for Health Care, because it establishes effective method of early prediction for many different diseases, creates a basis for prophylaxis. Reader has a chance to get rid of old dogmas and acquire new instrument for fruitful theoretical reasoning, research planning and predictive/preventive practical medical work.

Frontiers in Clinical Drug Research - Anti-Allergy Agents is an exciting eBook series comprising a selection of updated review articles relevant to the recent development of pharmacological agents used for the treatment of allergies. The scope of the reviews includes clinical trials of anti-inflammatory and anti-allergic drugs, drug delivery strategies used to treat specific allergies (such as inflammation, asthma and dermatological allergies), lifestyle dependent modes of therapies and the immunological or metabolic mechanisms that are of interest to researchers as targets for new drugs. The first volume of this series sheds light on new therapies that can be employed for allergic reactions in patients (both traditional and non-traditional therapies), nutrition based therapies and the use of substances such as omalizumab and adrenaline to counter inflammatory response and anaphylaxis in patients. </p><p> Frontiers in Clinical Drug Research - Anti-Allergy Agents will be of interest to immunologists and drug discovery researchers interested in anti-allergic drug therapy as the series provides relevant cutting edge reviews written by experts in this rapidly expanding field.

The endocannabinoid system comprises at least two G-protein-coupled receptors (the cannabinoid CB1 and CB2 receptors) activated by marijuana’s psychoactive principle ∆9-tetrahydrocannabinol (THC) and the endogenous ligands known as endocannabinoids. The apex of endocannabinoid research seems to have been reached with the clinical development, and also in some cases, the marketing, of synthetic or natural pharmaceuticals targeting this signalling system, which followed the understanding of the physiological and pathological role of endocannabinoids in several conditions, a role that was investigated first in rodent experimental models and then in humans. </p><p> Endocannabinoids: Molecular, Pharmacological, Behavioral and Clinical Features is a monograph that presents interesting manuscripts selected by the editor on the subject. Chapters in this book include original research or reviews which report the relevance of the endocannabinoid system by describing the results of experimental evidence about the neurobiological role of the endocannabinoid system. The main topics include, but are not limited to: </p><p> *The genetics of cannabinoid CB1 and CB2 receptors and their tissue distribution, their splicing variants and polymorphisms, and the possible implications of all this in determining different behaviours as well as various pathological conditions and the addiction to substances of abuse. </p><p> *Pharmacological approaches describing the potential use in the central nervous system disorders of endocannabinoid-based drugs, such as cannabinoid receptor agonists and antagonists, inhibitors of endocannabinoid inactivation processes, and even plant cannabinoids other than THC and with a molecular mechanism of action. </p><p> *The role of the endocannabinoid system in several neurological and neuropsychiatric conditions, such as epilepsy. </p><p> The volume would be a great interest to neuropharmacologists, physiologists and biochemists who aim to learn about the endocannabinoid system in detail.

Since a September, 1992, Nature article which read: “Can there be life without LIF?”, researchers now realize that the maternal immune system is both a foe (it can reject the conception) and a friend (immune cells and molecules are also necessary for successful pregnancy). Leukemia Inhibitory Factor (LIF) when absent, prevents embryo implantation in rodents. From fecundation to parturition, immunity acts as a Janus, required but potentially dangerous. However, the complexity and the diversity of immunity in pregnancy deters many from entering the field. This book will try to give a complete overview of immunity from gametes till parturition, in brief, but with complete chapters and subsections, each written by specialists in the field. The importance of the topic relies not only on “the riddle of the fetal allograft”, which is per se fascinating, but on its consequences, linked to the development of IVF and in general, Assisted Reproductive Technologies (ART) / Medicine. Since the discovery that there would not be (mammalian) life without LIF, it has become clear that Immune Molecules, and in general, transient post mating inflammatory reactions are required for successful implantation. Disruptions of this process can lead to implantation failure / sterility. In later stages of pregnancy immunological cells, mostly of the innate immune system, control formation of local spiral arteries. Finally, a state of tolerance establishes itself, whose “break’ leads to immune abortion and the vascular bed is further transformed and enlarged, till delivery, and here again “immunological cytokines” do play a major role and can eventually cause immune mediated abortion. Failure of, not just, the cytokine and cell recognition mediated dialogue, but also the pre and peri-implantation “preparation of the uterus”, as stated, leads to sterility, early pregnancy loss and recurrent abortions. There is also an increasingly stronger argument to implicate immunology in pre-eclampsia. Further still, immunology is also implicated in the control of local infection, mother to child transmission of pathogens (notably, but not limited to, HIV). Finally, pregnancy is the only known physiological phenomenon where the once named “suppressor T cells,” re-emerge as “regulatory T cells”, and play a cardinal role. This E-book provides a complete compendium of gynecological immunology, spanning from fecundation to delivery. Topics also include the role of various cell types (such as T regs ad NK cells) in implantation and uterine changes as well as the genetic regulation of immunological processes. As such it will be of interest not only to fundamental and reproductive immunologists, but more importantly, clinicians in obstetrics and gynecology.

Frontiers in Clinical Drug Research - Anti-Allergy Agents is an exciting eBook series comprising a selection of updated review articles relevant to the recent development of pharmacological agents used for the treatment of allergies. The scope of the reviews includes clinical trials of anti-inflammatory and anti-allergic drugs, drug delivery strategies used to treat specific allergies (such as inflammation, asthma and dermatological allergies), lifestyle dependent modes of therapies and the immunological or metabolic mechanisms that are of interest to researchers as targets for new drugs. The second volume of this series brings 7 reviews which cover neuro- and immunomodulating therapies for asthma and COPD, antioxidant therapies for allergies, allergic rhinitis medications and more. Frontiers in Clinical Drug Research - Anti-Allergy Agents will be of interest to immunologists and drug discovery researchers interested in anti-allergic drug therapy as the series provides relevant cutting edge reviews written by experts in this rapidly expanding field.