The aim and scope of this book is to highlight the sources, isolation, characterization and applications of bioactive compounds from the marine environment and to discuss how marine bioactive compounds represent a major market application in food and other industries. It discusses sustainable marine resources of macroalgal origin and gives examples of bioactive compounds isolated from these and other resources, including marine by-product and fisheries waste streams. In addition, it looks at the importance of correct taxonomic characterization."

Clinical pharmacology plays an important role in today's medicine. Due to the high sensitivity, selectivity, and affordability of a mass spectrometer (MS), the high performance liquid chromatography - mass spectrometry (LC-MS) analytical technique is widely used in the determination of drugs in human biological matrixes for clinical pharmacology. Specifically, LC-MS is used to analyze: anticancer drugs antidementia drugs antidepressant drugs antiepileptic drugs antifundal drug antimicrobial drugs antipsychotic drugs antiretroviral drugs anxiolytic/hypnotic drugs cardiac drugs drugs for addiction immunosuppressant drugs mood stabilizer drugs This book will primarily cover the various methods of validation for LC-MS techniques and applications used in modern clinical pharmacology.

Long acting injections and implants improve therapy, enhance patient compliance, improve dosing convenience, and are the most appropriate formulation choice for drugs that undergo extensive first pass metabolism or that exhibit poor oral bioavailability. An intriguing variety of technologies have been developed to provide long acting injections and implants. Many considerations need to go into the design of these systems in order to translate a concept from the lab bench to actual therapy for a patient. This book surveys and summarizes the field.

Topics covered in "Long Acting Injections and Implants" include the historical development of the field, drugs, diseases and clinical applications for long acting injections and implants, anatomy and physiology for these systems, specific injectable technologies (including lipophilic solutions, aqueous suspensions, microspheres, liposomes, in situ forming depots and self-assembling lipid formulations), specific implantable technologies (including osmotic implants, drug eluting stents and microfabricated systems), peptide, protein and vaccine delivery, sterilization, drug release testing and regulatory aspects of long acting injections and implants.

This volume provides essential information for experienced development professionals but was also written to be useful for scientists just beginning work in the field and for others who need an understanding of long acting injections and implants. This book will also be ideal as a graduate textbook."

Alzheimer's Disease is a progressive neurodegenerative disorder of late life with devastating consequences for the afflicted and their carers and poses one of the major challenges to medical research. Until recently, little hope of effective therapies capable of slowing the disease process or preventing its occurrence was apparent. With recent advances in the genetics and molecular biology of the disease processes and the demonstration of the involvement of multiple aetiological factors, however, real chances are now appearing for the identification of preventive drugs. In this discussion, experts from disciplines ranging from molecular genetics to the clinic provide review and novel data concerning the aetiology of AD and the establishment of drugfinding screening methods.

to Cyclic glucans are polysaccharides that are predominantly produced by "Agrobacterium, Bradyrhizobium" and "Rhizobium "sp. and widely used in the pharmaceutical and food industries. In this book, the applications, properties, analytical tools, production and genes of four main cyclic -glucans from microorganisms are highlighted and critically evaluated. As biocompatible and biodegradable renewable resources, they have an immense potential for future applications, which has not yet been fully exploited. This concise review will help to bridge this gap."

Chronic inflammation is one of the major pathological bases manifesting the development of gastric cancers, hepatitis and hepatocellular carcinoma, cervical cancer, ulcerative colitis and colorectal cancer [1]. Microbial infections, viral infections and autoimmune responses can lead to chronic inflammation-associated cancer formation. Human herpesviruses, such as human cytomegalovirus (HCMV) and Kaposi sarcoma herpesvirus (KSHV) are known to be associated with tumorigenesis and tumor progression. HCMV infection potentiates malignancies of colon cancer and malignant glioma [2,3]. KSHV was initially discovered from Kaposi's sarcoma lesion of an AIDS patient [4]. It was subsequently discovered that KSHV contributed to the pathogenesis of KS, primary effusion lymphoma [5] and lymphoproliferative disorder multicentric Castleman's disease. Emerging evidence shows that herpesvirus infection interferes or inhibits host cell immune defense and maintains a tumor-promoting microenvironment by expressing virulent homologues of host cell proteins that disturb normal cell cycle progression and leads to apoptosis of the host cells. For example, cellular growth and transformation are induced by viral-encoded homologues of cytokines, chemokines or chemokine receptors [6]. The constitutive expression of viral chemokine GPCRs triggers prolonged activation of G protein signaling and eventually becomes the major inputs for chronic leukocyte infiltration and cancer development. GPCRs can serve as proto-oncogenes since overexpression of various wild type GPCRs can transform cells in the presence of their specific ligands. Mutations on GPCRs may result in constitutive signaling and oncogenesis [7]. Naturally occurring mutations in GPCRs have been identified in human tumors [8,9].

Jason Woolford's thesis describes for the first time, a double 3]2] photocycloaddition of alkenes onto aromatic rings. Modern synthetic chemistry relies on the ability of researchers to uncover new and more efficient ways of creating highly complex structures. This work describes a novel, environmentally friendly photochemical step that converts in one pot, trivial starting materials into otherwise difficult to construct fenstrane frameworks. The rigid cores of these frameworks have significant potential in drug design. Moreover, the novelty of this work overtakes many other methods for the creation of chiral centres. No less than seven chiral centres are created in the photochemical step together with the formation of four carbon-carbon bonds and multifused rings. Jason's innovative work has been the subject of several publications in peer-reviewed journals."

It is increasingly recognized that various transporter proteins are expressed throughout the body and determine absorption, tissue distribution, biliary and renal elimination of endogenous compounds and drugs and drug effects. This book will give an overview on the transporter families which are most important for drug therapy. Most chapters will focus on one transporter family highlighting tissue expression, substrates, inhibitors, knock-out mouse models and clinical studies.

Hypertension has certainly been one of the topics most fre quently discussed at symposia, meetings, and congresses during recent years. There may be several reasons for this; three of them are obvious: firstly, the fact that a large proportion of the world's population is suffering from various forms of hypertensive disease; secondly, increasing knowledge of the pathogenesis of hypertension and of the disturbances underlying it; and, thirdly, the marked progress which has been made in antihypertensive therapy over the past fifteen years. When plans for the present symposium were being drawn up, it was felt that it should not simply bring forth just another meeting on hypertension, but should place particular emphasis on those aspects which had not been adequately discussed at previous symposia of this kind. Curiously enough, the topic which appeared to have received least attention in the past was therapy, although from the practical point of view this is by far the most important. The choice of therapy as the main theme of the whole symposium also seemed to be warranted in view of the relatively long period that had elapsed since effective antihyper tensive treatment became available; the time had in fact come now to pass judgement on the benefits as well as the shortcomings of drug treatment as available today.

Complied by an expert editorial team with noteworthy and remarkable experience, this book covers technological aspects related to probiotics, not only in terms of delivery modes but also in terms of protection technologies. It includes discussions of their therapeutic and physiologic implications and benefits, and provides a contemporary update and a holistic review of the topic. It focuses on the technological aspects of probiotic products, brings together the information needed for their successful development, and examines the international picture regarding regulatory issues.

Written by internationally acclaimed experts in the economics of innovation, this volume examines how the biotechnology and pharmaceutical sector is affected by the dynamics of innovation, institutions, and public policy. It contributes both theoretically and empirically to the increasingly influential Schumpetarian framework in industrial economics, which places innovation at the centre of the analysis of competition. Both quantitative and qualitative studies are included, and this varied perspective adds to the richness of the volume's insights. The contributors explore different ideas regarding the historical evolution of technology in the sector, and how firms and industry structure have co-evolved with innovation dynamics. Important policy questions are considered regarding the future of innovation in this sector and its impact on the economy.

Trials in the treatment of the leukemias are sometimes based on a hypothesis, as in the case of exchange transfusion [33] or the use of antimetabolites [86]. Or they are conducted empirically as the results of chance observations, as in the case of the use of the nitrogen mustards, urethane, and the Vinca alkaloids. Or they lie between the two, aiming at making use of well established biological facts: examples are the use of ACTH, cortisone and, more recently, the antibiotics. What is true for bacteria may also perhaps be true, if not for elephants, at least for the malignant cells of mammals. It was this idea that lay behind the first attempts at treating cancer and leukemia with antibiotics. The results obtained by the use of certain substances extracted from micro-organisms (actinomycin, azaserine, mito mycin, rufocromomycin), although encouraging at times, were inconsistent. The action of rubidomycin appears to cover a wider spectrum and to be more consistent and more effective. As in the case of Homer and Christopher Columbus, the honor of having given birth to rubidomycin is claimed by more than one country and town. In fact, the same product was discovered in the same year, though quite independently, by a group of French workers [184] who described it under the name of rubidomycin, and by a group of Italian workers [87] who studied it under the name of daunomycin.

Pharmaceutical Biotechnology is a unique compilation of reviews addressing frontiers in biologicals as a rich source for innovative medicines. This book fulfills the needs of a broad community of scientists interested in biologicals from diverse perspectives basic research, biotechnology, protein engineering, protein delivery, medicines, pharmaceuticals and vaccinology. The diverse topics range from advanced biotechnologies aimed to introduce novel, potent engineered vaccines of unprecedented efficacy and safety for a wide scope of human diseases to natural products, small peptides and polypeptides engineered for discrete prophylaxis and therapeutic purposes. Modern biologicals promise to dramatically expand the scope of preventive medicine beyond the infectious disease arena into broad applications in immune and cancer treatment, as exemplified by anti-EGFR receptors antibodies for the treatment of breast cancer. The exponential growth in biologicals such as engineered proteins and vaccines has been boosted by unprecedented scientific breakthroughs made in the past decades culminating in an in-depth fundamental understanding of the scientific underpinnings of immune mechanisms together with knowledge of protein and peptide scaffolds that can be deliberately manipulated. This has in turn led to new strategies and processes. Deciphering the human, mammalian and numerous pathogens genomes provides opportunities that never before have been available identification of discrete antigens (genomes and antigenomes) that lend themselves to considerably improved antigens and monoclonal antibodies, which with more sophisticated engineered adjuvants and agonists of pattern recognition receptors present in immune cells, deliver unprecedented safety and efficacy. Technological development such a nanobiotechnologies (dendrimers, nanobodies and fullerenes), biological particles (viral-like particles and bacterial ghosts) and innovative vectors (replication-competent attenuated, replication-incompetent recombinant and defective helper-dependent vectors) fulfill a broad range of cutting-edge research, drug discovery and delivery applications. Most recent examples of breakthrough biologicals include the human papilloma virus vaccine (HPV, prevention of women genital cancer) and the multivalent Pneumoccocal vaccines, which has virtually eradicated in some populations a most prevalent bacterial ear infection (i.e., otitis media). It is expected that in the years to come similar success will be obtained in the development of vaccines for diseases which still represent major threats for human health, such as AIDS, as well as for the generation of improved vaccines against diseases like pandemic flu for which vaccines are currently available. Furthermore, advances in comparative immunology and innate immunity revealed opportunities for innovative strategies for ever smaller biologicals and vaccines derived from species such as llama and sharks, which carry tremendous potential for innovative biologicals already in development stages in many pharmaceutical companies. Such recent discoveries and knowledge exploitations hold the promise for breakthrough biologicals, with the coming decade. Finally, this book caters to individuals not directly engaged in the pharmaceutical drug discovery process via a chapter outlining discovery, preclinical development, clinical development and translational medicine issues that are critical the drug development process.

The authors and editors hope that this compilation of reviews will help readers rapidly and completely update knowledge and understanding of the frontiers in pharmaceutical biotechnologies."

Analytical chemists in the pharmaceutical industry are always looking for more-efficient techniques to meet the analytical challenges of today s pharmaceutical industry. One technique that has made steady advances in pharmaceutical analysis is supercritical fluid chromatography (SFC). SFC is meeting the chromatography needs of the industry by providing efficient and selective testing capabilities on the analytical and preparative scale. The supercritical fluid mobile phase, consisting mainly of CO2, facilitates cost reduction costs and helps the industry in meeting green chemistry standards. This book provides a comprehensive overview of the use of SFC in pharmaceutical analysis.

Supercritical Fluid Chromatography reviews the use of SFC in drug-discovery applications and describes its application in drug development. When a drug is developed and brought to market, it is tested many times for impurities and degradants, enantiomeric purity, and analytical and preparative isolations it is tested during discovery and development and for under-regulated and unregulated methodologies. The book describes the use of SFC for each of these applications and discusses more in-depth topics, such as the use of SFC in mass spectrometric and polarographic detection. The book also sheds light on the role of SFC in drug development from natural products and the advancement of SFC with new technologies and its use in pilot-scale operations as a chromatographic technique.

Melville's Monumental Imagination explores the connection between the contested 19th century American monument tradition and one of the nation's most revered authors, Herman Melville (1819-1891). The book was written to fill a void in recent Melville scholarship. To date, there has not been a monograph that focuses exclusively on Melville's incorporation of monuments in his fictional world. The book charts the territory of Melville's novels in order to provide a trajectory of the monumental image in one particular literary form. This feature allows the reader to gradually see the monumental image as an important marker that sheds light into Melville's eventual abandonment of long fiction. Melville'sMonumental Imagination combines literary analysis and cultural criticism for a long neglected aspect of our nation's iconic development in statuary.

A team of expert investigators and clinical researchers comprehensively review complement's basic biology, its role in disease, methods to measure its activity, and strategies for its inhibition in patients. Each chapter focuses on a specific area of basic and applied complement biology, spelling out the activation pathways and complement receptors. Informative animal models are discussed in detail, including the relative values of each model and the important interspecies differences that can distort the interpretation of preclinical studies. The emphasis throughout is on the pros and cons of the therapeutic use of recombinant complement inhibitors in specific diseases. Cutting-edge and innovative, Therapeutic Interventions in the Complement System highlights for today's researcher and biotechnologist effective strategies of drug discovery and development that are producing valuable new complement inhibitors for the treatment of a wide variety of clinically important diseases.

Recent reviews of respiratory-tract affections caused by M. pneumoniae under- score the benign and often subclinical course of the infection. Severe pneumonia with a reticular or acinar pattern is certainly unusual and a fatal outcome is rare, but the incidence of both is underestimated. Erythromycin and tetracyclines are the first-choice antibiotics. There is evidence indicating the importance of im- munopathogenic mechanism in provoking pneumonia and even respiratory failure. REFERENCES 1. Krech U, Price PC, Jung M: The laboratory diagnosis and epidemiology of mycoplasma pneumoniae in Switzerland. Infection 4:33, 1976. 2. Fischman RA, Marschall KE, Kislak JW: Adult respiratory distress syndrome caused by mycoplasma pneumoniae. Chest 74:471, 1978. 3. Reigner Ph, Domenighetti G, Feihl F, Bonjour JPh, Perret CI: Syndrome de detresse respiratoire aigu sur infection a mycoplasme. Sch Med W 110:220, 1980. 4. Kaufman JM, Cuvelier CA, Van der Straeten M: Mycoplasma pneumonia with fulminant evolution into diffuse interstitial fibrosis. Thorax 35:140, 1980. 5. Murray HW, Masur H, Senterfit L, Roberts R: The protean manifestations of mycoplasma pneumoniae infection in adults. Am J Med 58:229, 1975. 6. Levine DP, Lerner AM: The clinical spectrum of Mycoplasma pneumoniae infections. Med Clin N Am 62:961,1978. 7. Twomey JA, Espir ML: Neurological manifestations and Mycoplasma pneumoniae infection. BMJ 2:832, 1979. 8. Kingston JR, Chankock RM, Mufson MA, Hellman LP, James WD, Fox HH, Mankoma C, Boyers J: Eaton agent pneumonia. JAMA 176:118, 1961.

In summary, there are many animal models that are useful in selecting new antiarrhythmic drugs. The selection of which model is most idea depends upon precisely what question is being asked. The large number of experimental models used to evaluate antiarrhythmic compounds points out the inability of anyone model to define the probability of antiarrhythmic efficacy in man. It has therefore become standard practice to utilize a batter of animal models for the evaluation of new antiarrhythmic agents. Each model has its own advantages and disadvantages and it is necessary to understand each model fully in oder to evaluate experimental findings and apply them to clinical settings. We believe that the availability of the chronic myocardial infarction ventricular tachyarrhythmia model provides 1) an excellent opportunity to more precisely understand arrhythmia mechanisms, 2) to develop new techniques such as signal averaging for evaluating late low level potentials identifying hearts at high risk of sudden death 3) to identify new antifibrillatory drugs versus drugs that are effective primarily against PVC's and ventricular tachycardia 4) to identify new surgical techniques to eliminate VT/VF, and 5) to evaluate new pacing modalities including implantable cardioverters. Although all animal models are wrong, many are very useful in furthering our knowledge directed at decreasing the distressingly high mortality from heart disease. NORMAL HtART TACHYCMDIA HtART , .. '" \ I I I I I I I I I .

Packed with real-world examples, this book illustrates the 12 principles of green chemistry. These diverse case studies demonstrate to scientists and students that beyond the theory, the challenges of green chemistry in pharmaceutical discovery and development remain an ongoing endeavor. By informing and welcoming additional practitioners to this mission, the negative environmental impact of pharmaceutical products will continue to be minimized. Green chemistry is the methodology by which chemical production in this industry can become more efficient, adding environmental stewardship to the noble mission of treating human disease.

First published in 1989, this book acknowledges that new drugs, food additives and other compounds need to be carefully screened for toxic side-effects. The bulk of this study is devoted to the practical questions of 'what toxicological studies should we perform?' and 'how should we perform them?' Compounds which undergo toxicity testing may be conveniently categorised as those which are intended for administration to man and those which are not. The former include pharmaceuticals to be used medicinally or prophylactically and chemicals which are added to our food, drinks or medicine to improve their stability, appearance or palatability. Since it is on pharmaceuticals that the most comprehensive toxicological evaluations are generally performed, this book has been directed primarily towards to toxicological evaluation of potential new drugs. The principles and methodology of toxicological evaluation of other types of compounds are essentially similar.

The use of honey can be traced back to the Stone Age. Evidence can be found for its nutritional and medicinal use beginning with prehistoric and ancient civilizations. Currently, there is a resurgence of scientific interest in natural medicinal products, such as honey, by researchers, the medical community, and even the general public. Honey in Traditional and Modern Medicine provides a detailed compendium on the medical uses of honey, presenting its enormous potential and its limitations. The book covers honey's ethnomedicinal uses, chemical composition, and physical properties. It discusses the healing properties of honey, including antimicrobial, anti-inflammatory, and antioxidant properties. It also examines the botanical origin of honey, a critical factor in relation to its medicinal use, along with the complex subject of the varying composition of honey. Honey's antibacterial qualities and other attributes are described in a chapter dedicated to Leptospermum, or Manuka honey, a unique honey with potential for novel therapeutic applications. Chapters explore a variety of medicinal uses for honey, including its healing properties and use in burn and wound management. They review honey's beneficial effects on medical conditions, such as gastrointestinal disorders, cardiovascular diseases, diabetic ulcers, and cancers as well as in pediatrics and animal health and wellness. The book also examines honey-based formulations, modern methods for chemical analysis of honey, and the history and reality of "mad honey." The final chapters cover honey in the food industry, as a nutrient, and for culinary use.

Cutting-edge researchers describe their efforts to design, synthesize, and evaluate the biological activities of farensyltransferase inhibitors (FTIs); geranylgeranyltransferase inhibitors (GGTIs) are also discussed as potential anticancer drugs. The authors survey in detail such inhibitors as CAAX box peptidomimetics, FPP mimics, and bisubstrate transition state analogs, and critically review their uses in combination with radiation and other cytotoxic agents, such as gemcitabine, cisplatin, and taxanes. Illuminating and richly detailed, Farnesyltransferase Inhibitors in Cancer Therapy constitutes today's standard reference for the pathbreaking use of FTIs and GGTIs in anticancer therapy and offers basic and clinical investigators a comprehensive treatment of the scientific and medical aspects of farnesyltransferase inhibitors.

Macromolecular (specifically peptide-based) drugs could potentially be highly effective medicines. However they have a relatively short duration of action and variable therapeutic index. An example of such a peptide is Glucagon-like Peptide I which could potentially be used as a revolutionary drug for diabetes. This is because it stimulates insulin only when the blood glucose level is high thereby reducing the risk of hypoglycemia (a significant disadvantage of using insulin is that an insulin overdose is the single most potent cause of life-threatening hypoglycemia). However it's short duration of action (half-life of 2 minutes in plasma) precludes its therapeutic use. In this volume, the use of novel therapeutics like GLP1 as an alternative to tradition insulin-based drugs in diabetes is described. Application of Peptide-Based Prodrug Chemistry in Drug Development elucidates the traditional concept of prodrugs as "specialized non-toxic protective groups used in a transient manner to alter or to eliminate certain limiting properties in the parent small molecule" (IUPAC definition). It goes on to provide insight into how prodrugs of peptides (with GLP1 as an example) could be appropriately used to extend the biological half life, broaden the therapeutic index of macromolecules and improve the pharmacodynamics of such drugs. Author explains the logic behind designing peptide prodrugs, synthetic procedures and bioassays to examine the conversion of the prodrug to the drug under therapeutic conditions. The prodrugs described slowly convert to the parent drug at physiological conditions of 37C and pH 7.2 driven by their inherent chemical instability without the need of any enzymatic cleavage. The diketopiperazine and diketomorpholine (DKP and DMP) strategies for prodrug conversion are demonstrated in detail with special emphasis on the chemical flexibility that it offers to develop prodrugs with variable time actions. This book will be of useful to chemists, biochemists, medicinal chemists, biologists and people in the medical profession (doctors). It may be used in undergraduate classes but will certainly help post-graduate students and advanced professionals. The author is grateful to Prof. Richard DiMarchi (Standiford H. Cox Professor of Chemistry and the Linda & Jack Gill Chair in Biomolecular Sciences at Indiana University) for valuable suggestions. The foreword for the book has been written by Prof. Jean Martinez, (Legion d'Honneur awarded by the French Republic; Professor of Chemistry and Medicinal Chemistry of the University of Montpellier, France; and Chairman of European Peptide Society, 2002-2010).

The first authoritative overview of past and current strategies for successful drug development by analog generation, this unique resource spans all important drug classes and all major therapeutic fields, including histamine antagonists, ACE inhibitors, beta blockers, opioids, quinolone antibiotics, steroids and anticancer platinum compounds.

Of the 19 analog classes presented in detail, 9 are described by the scientists who discoverd them.

The book includes a table of the most successful drug analogs as based on the IMS ranking and compares them in terms of chemical structure, mode of action and patentability.

This Brief discusses key statistical concepts that facilitate the inferential analysis of data collected from a group of individuals participating in a pharmaceutical clinical trial, the estimation of their clinical significance in the general population of individuals likely to be prescribed the drug if approved, and the related decision-making that occurs at both the public health level (by regulatory agencies when deciding whether or not to approve a new drug for marketing) and the individual patient level (by physicians and their patients when deciding whether or not the patient should be prescribed a drug that is on the market). These concepts include drug safety and efficacy, statistical significance, clinical significance, and benefit-risk balance.